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Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery
Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Malignant Neoplasm; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
... your gallbladder and liver to your small intestine. Cancer of the gallbladder is rare. It is more ... the abdomen It is hard to diagnose gallbladder cancer in its early stages. Sometimes doctors find it ...
Machado, Norman O.
Gallbladder calcification, also referred to as porcelain gallbladder, has received significant attention in the medical literature due to its perceived role in increasing the risk of developing a gallbladder carcinoma. However, recent reports raise questions challenging this purported high risk. While previous studies reported a concomitant incidence of gallbladder cancer in porcelain gallbladder ranging from 7–60%, more recent analyses indicate the incidence to be much lower (6%). Based on evidence in the current literature, a prophylactic cholecystectomy is not routinely recommended for all patients with porcelain gallbladder and should be restricted to those with conventional indications, such as young patients. However, it is important to note that a nonoperative approach may require prolonged follow-up. A laparoscopic cholecystectomy is a feasible therapeutic option for patients with porcelain gallbladder, although some researchers have indicated a higher incidence of complications and conversion due to technical difficulties. PMID:28003886
Ece, İlhan; Alptekin, Hüsnü; Çelik, Zeliha Esin; Şahin, Mustafa
Gallbladder paraganglioma is a very rare tumor, and only a few cases have been reported. Most of these cases were asymptomatic and found incidentally during operation. Our case involved a 57-year-old female patient complaining of intermittent right upper quadrant pain. Preoperative imaging demonstrated a mass in the neck of the gallbladder. Laparoscopic cholecystectomy was performed, and a frozen section of the gallbladder demonstrated a benign mass. The postoperative pathologic examination reported gallbladder paraganglioma and chronic cholecystitis. Immunohistochemically, the chief cells and sustentacular cells showed diffuse positivity with vimentin, synaptophysin, and S-100.
Patrlj, Leonardo; Kopljar, Mario; Kliček, Robert; Kolovrat, Marijan; Loncar, Bozo; Busic, Zeljko
Gallbladder cancer is the fifth most common cancer involving gastrointestinal tract, but it is the most common malignancy of the biliary tract, accounting for 80-95% of biliary tract cancers. This tumor is a highly lethal disease with an overall 5-year survival of less than 5% and mean survival mere than 6 months. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. Patients with preoperative suspicion of gallbladder cancer should not be treated by laparoscopy. Epidemiological studies have identified striking geographic and ethnic disparities—inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Improved imaging modalities and improved radical aggressive surgical approach in the last decade has improved outcomes and helped prolong survival in patients with gallbladder cancer. The overall 5-year survival for patients with gallbladder cancer who underwent R0 curative resection was from 21% to 69%. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. PMID:25392833
Biswas, P K
Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.
Mink van der Molen, A B; Salu, M K
A 59-year-old woman is described with symptomatic cholelithiasis. A double gallbladder was incidentally found during abdominal surgery. The literature on a double gallbladder is reviewed with respect to incidence, anatomy, diagnosis and therapy.
... Cancer > Gallbladder Cancer: Overview Request Permissions Gallbladder Cancer: Overview Approved by the Cancer.Net Editorial Board , 08/ ... as it grows. Looking for More of an Overview? If you would like additional introductory information, explore ...
Gallbladder cancer and nutritional risk factors in Chile
Navarro Rosenblatt, Deborah; Durán Agüero, Samuel
Gallbladder cancer is the most malign neoplasm of the biliary tract. Chile presents the third highest prevalence of gallbladder cancer in the Americas, being Chilean women from the city of Valdivia the ones with the highest prevalence. The main risk factors associated with gallbladder cancer are: sex, cholelithiasis, obesity, ethnicity, chronic inflammation, history of infection diseases such as Helicobacter pyloriand Salmonellaand family history of gallbladder cancer. In Chile gallbladder cancer mortality is close to prevalence level. This is related to the silent symptomatology of this cancer, as well as the lack of specific symptoms. The high prevalence of obesity and infectious diseases present in Chile are two of the main risk factors of gallbladder cancer and Chile has prevalence of obesity close to 30%. The aim of this literary review is to inform and summarize the main risk factors of gallbladder cancer that are prevalent in Chile, in order to be able to focus preventive and management interventions of this risk factor for the reduction in prevalence and mortality of gallbladder cancer in Chile.
Tuberculosis of the Gallbladder
Kumar, K.; Ayub, M.; Kumar, Mohan; Keswani, N. K.
Analysis of 5 patients with gallbladder tuberculosis who had open cholecystectomy and review of literature have shown that, although still rare it presents as a part of systemic miliary tuberculosis, abdominal tuberculosis, isolated gallbladder tuberculosis and as acalculus cholecystitis in anergic patients. There are no pathognomonic signs, the diagnosis depends on suspicion of tuberculosis, peroperative findings and histological examination. PMID:10977119
Myelodysplastic/ Myeloproliferative Neoplasms Treatment
... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...
Chronic Myeloproliferative Neoplasms Treatment
... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...
... the surgeon needs to switch to an open surgery if laparoscopic surgery cannot be successfully continued. Other reasons for removing the gallbladder by open surgery: Unexpected bleeding during the laparoscopic operation Obesity Pancreatitis (inflammation in the pancreas) Pregnancy ( ...
Gallbladder removal - laparoscopic
... if you have pain or other symptoms from gallstones . You may also need it if your gallbladder ... series References Glasgow RE, Mulvihill SJ. Treatment of gallstone disease: In: Feldman M, Friedman LS, Brandt LJ, ...
... Serosal (outer) layer. Between these layers is supporting connective tissue . Primary gallbladder cancer starts in the inner layer ... has spread beyond the muscle layer to the connective tissue around the muscle. Stage IIIA In stage IIIA , ...
Chemotherapy for Gallbladder Cancer
... often used for gallbladder cancer include: Gemcitabine (Gemzar ® ) Cisplatin (Platinol ® ) 5-fluorouracil (5-FU) Capecitabine (Xeloda ® ) Oxaliplatin ( ... them more effective. For example, combining gemcitabine and cisplatin may help people live longer than getting just ...
Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy
Mixed adenoneuroendocrine carcinoma (MANEC) carcinomas rarely occur in the gallbladder. Here we reported a case of giant gallbladder unresectable mass with local liver invasion and omentum metastasis, which proved to be neuroendocrine carcinoma (NEC) by biopsy, received successful radical operation after neo-adjuvant chemotherapy plus somatostatin treatment. The patient showed good response as the neoplasm diminished dramatically and showed clear margin after 6 courses of treatment. A radical operation including cholecystectomy, hepatic wedge resection of the gallbladder fossa segment and lymph node of group 8a and 8p resection was performed successfully. Postoperative histopathological examination revealed neuroendocrine carcinoma mixed with adenocarcinoma in the gallbladder wall. Followed up showed no evidence of recurrence after 7 months of the operation. We suggest that neo-adjuvant chemotherapy may be beneficial to gallbladder mixed neuroendocrine carcinomas in an advanced stage which could also be advantageous to NEC of other organs. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2731892837743787 PMID:23186166
Ultrasound evaluation of centenarians' gallbladder.
Romano, Marcello; Batticani, Santa; Pistone, Giovanni; Malaguarnera, Mariano
Background: Ultrasound (US) examination of gallbladder is considered to be reliable, both in morphological and functional evaluation. We used US to study the gallbladder of a series of centenarians in order to show the characteristics of this organ in these subjects. We then compared the data obtained with two control populations omposed of elderly and adult subjects, respectively. Methods: US examination was done after an overnight fast and after emptying the gallbladder at 15-min intervals for a period of 90 min. To induce emptying of the gallbladder, we chose a semisolid meal with a small caloric value (370 kcal). The following parameters were evaluated: fasting gallbladder volume (in milliliters) before administration of the meal (considered to be 100%); gallbladder emptying (according to the formula: fasting gallbladder volume minus post-meal gallbladder volume at 10-min intervals divided by fasting gallbladder volume: the result of this operation was multiplied by 100); gallbladder motor functions, such as ejection volume (ml), is considered as the difference between fasting gallbladder volume and residual volume; ejection fraction (%), considered as the difference between fasting gallbladder volume and residual volume, is expressed as percentage fasting volume; and ejection rate (%/min) is calculated by dividing ejection fraction by time requested to reach the residual volume. Results: We found a common bile duct diameter that was significantly higher in centenarians than in the elderly and adults. Gallbladder wall thickness was significantly higher in centenarians than in adults. We also found substantially significant differences between centenarians with and without gallstones and elderly and adult subjects in the following parameters: mean gallbladder volume (reduced), residual volume (reduced), ejection volume (reduced) and ejection rate (reduced). The differences were not significant for the ejection fraction, and they were slightly reduced in
Biliary and gallbladder dyskinesia.
George, Josh; Baillie, John
Gallbladder and biliary dyskinesia are conditions that are becoming increasingly recognized due to improved technology. They are motility disorders that affect the gallbladder and sphincter of Oddi (SO), respectively. Gallbladder dyskinesia presents with typical biliary pain in the absence of gallstones. Work-up includes laboratory tests and imaging to rule out gallstones. Further investigation leads to a functional radionuclide study to investigate gallbladder ejection fraction. An ejection fraction of less than 40% is considered abnormal, and patients should be referred for cholecystectomy. Symptom relief after the procedure has been seen in 94% to 98% of patients. The term sphincter of Oddi dysfunction (SOD) describes a collection of pain syndromes that are attributed to a motility disorder of the SO. SOD can be further subdivided into biliary and pancreatic SOD. Patients typically have had a prior cholecystectomy and present with episodic biliary pain. The initial work-up includes laboratory tests and imaging to rule out other structural causes of abdominal pain, such as retained gallstones. Imaging and laboratory studies further subdivide patients into types of SOD. SO manometry (SOM) is the gold standard for assessing biliary dyskinesia and can help stratify patients into one of two groups: SO stenosis versus SO dyskinesia. Those with stenosis (type I SOD) are the most likely to respond to treatment with endoscopic biliary sphincterotomy (EBS). As the vast majority of type I patients (>/= 90%) benefit from EBS, SOM is not necessary. Pancreatic SOD patients can be similarly divided into one of three groups. These patients present with recurrent bouts of abdominal pain and/or pancreatitis in the absence of gallstones or other structural abnormalities. Pancreatic sphincter manometry can help distinguish which patients would benefit from endoscopic pancreatic sphincterotomy. Recurrent stenosis of the opening after endoscopic treatment in these patients may
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
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Postmenopausal bleeding and vaginal nodules as the first presenting sign of adenocarcinoma of the gallbladder.
Triolo, O; Antico, F; Mancuso, A; Salimbeni, V; Nicotina, P A
Vaginal submucosal nodules were observed in a 67-year-old woman, with ultrasonographic features of an advanced uterine neoplasm. On biopsy, light microscopy suggested that the lesions might be metastatic foci from an extragenital cancer, with a prevalent tubular growth pattern. Parallel immunohistochemical reactions revealed a diffuse, strong CA 19-9 positivity in both the cell membrane and cytoplasm. Subsequently, high serum levels of such tumor marker were also found, and an extragenital cancer was suspected of pancreatic or biliary origin. A mass in the gallbladder fossa was then detected by computed tomography and a primary gallbladder adenocarcinoma was confirmed on ultrasound-guided biopsy.
Can Gallbladder Cancer Be Prevented?
... with gallstones have their gallbladder removed unless the stones are causing symptoms or other problems. This is ... Treatments & Side Effects Cancer Facts & Statistics News and Stories Glossary For Health Care Professionals Programs & Services Breast ...
Treatment Options for Gallbladder Cancer
... Serosal (outer) layer. Between these layers is supporting connective tissue . Primary gallbladder cancer starts in the inner layer ... has spread beyond the muscle layer to the connective tissue around the muscle. Stage IIIA In stage IIIA , ...
General Information about Gallbladder Cancer
... Serosal (outer) layer. Between these layers is supporting connective tissue . Primary gallbladder cancer starts in the inner layer ... has spread beyond the muscle layer to the connective tissue around the muscle. Stage IIIA In stage IIIA , ...
Treatment Option Overview (Gallbladder Cancer)
... Serosal (outer) layer. Between these layers is supporting connective tissue . Primary gallbladder cancer starts in the inner layer ... has spread beyond the muscle layer to the connective tissue around the muscle. Stage IIIA In stage IIIA , ...
Gallbladder function in diabetic patients
Shreiner, D.P.; Sarva, R.P.; Van Thiel, D.; Yingvorapant, N.
Gallbladder emptying and filling was studied in eight diabetic and six normal control patients. None of the patients had gallstones. Cholescintigraphy was performed using (/sup 99m/Tc)disofenin, and gallbladder emptying was studied using a 45-min i.v. infusion of the octapeptide of cholecystokinin (OP-CCK) 20 ng/kg X hr. The peak filling rate was greater in diabetic than in normal subjects; however, emptying of the gallbladder in response to OP-CCK was significantly less in the diabetic subjects (51.6 +/- 10.4% compared with 77.2 +/- 4.9%). When the diabetic group was subdivided into obese and nonobese diabetics, the obese diabetics had a much lower percentage of emptying than the nonobese diabetics (30.0 +/- 10.4% compared with 73.1 +/- 9.3%). These findings suggest that obese diabetics may have impaired emptying of the gallbladder even in the absence of gallstones. The more rapid rate of gallbladder filling in obesity may indicate hypotonicity of the gallbladder. The combination of these abnormalities may predispose the obese diabetic to the development of gallstones.
Signet-ring cell carcinoma of the gallbladder with skin metastases.
Krunic, Aleksandar L; Chen, Helen M; Lopatka, Keith
Cutaneous metastasis from gallbladder cancer is extremely rare. We present a case of signet-ring cell carcinoma of the gallbladder metastatic to the skin in a 38-year-old man. The skin nodules on the face, scalp and perianal area occurred approximately 1 year after the resection of the neoplasm. Skin metastases from gastrointestinal cancers are usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, and rarely present at other sites. Multiple imaging studies revealed the presence of metastatic bony involvement in the spine and left orbit. Visceral metastases have not been demonstrated in our patient in 20 months of follow up since the initial diagnosis of gallbladder cancer was made. We also briefly discuss other primary and metastatic skin tumours with signet-ring cell morphology.
Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles
MIZUTANI, Shinya; TORISU, Shidow; KANEKO, Yasuyuki; YAMAMOTO, Shushi; FUJIMOTO, Shinsuke; ONG, Benedict Huai Ern; NAGANOBU, Kiyokazu
The pathophysiology of canine gallbladder diseases, including biliary sludge, gallbladder mucoceles and gallstones, is poorly understood. This study aimed to evaluate the component of gallbladder contents and bacterial infection of the gallbladder in order to elucidate the pathophysiology of biliary sludge and gallbladder mucoceles. A total of 43 samples of canine gallbladder contents (biliary sludge, 21 and gallbladder mucoceles, 22) were subjected to component analysis by infrared spectroscopy, and the resultant infrared spectra were compared with that of swine mucin. Of the 43 samples, 41 were also evaluated by aerobic and anaerobic bacterial culture. The contents of 20 (95.2%) biliary sludge and 22 (100%) gallbladder mucocele samples exhibited similar infrared spectra as swine mucin. Although biliary sludge and gallbladder mucocele contents exhibited similar infrared spectra, one sample of biliary sludge (4.8%) was determined to be composed of proteins. The rate of bacterial infection of the gallbladder was 10.0% for biliary sludge and 14.3% for gallbladder mucoceles. Almost all of the identified bacterial species were intestinal flora. These results indicate that the principal components of gallbladder contents in both gallbladder mucoceles and biliary sludge are mucins and that both pathophysiologies exhibit low rates of bacterial infection of the gallbladder. Therefore, it is possible that gallbladder mucoceles and biliary sludge have the same pathophysiology, and, rather than being independent diseases, they could possibly represent a continuous disease. Thus, biliary sludge could be considered as the stage preceding the appearance of gallbladder mucoceles. PMID:27990011
The role of the gallbladder in humans.
Turumin, J L; Shanturov, V A; Turumina, H E
The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid) in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid), thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation and protecting the liver, the stomach mucosa, the gallbladder, and the colon from their toxic hydrophobic effects. The presence or absence of the gallbladder in mammals is a determining factor in the synthesis of hydrophobic or hydrophilic bile acids. Because the gallbladder contracts 5-20 min after food is in the stomach and the "gastric chyme" moves from the stomach to the duodenum 1-3 h later, the function of the gallbladder bile in digestion may be insignificant. The aim of this article was to provide a detailed review of the role of the gallbladder and the mechanisms related to bile formation in humans.
Spontaneous Perforation of Gallbladder: Case Report
Sheoran, Satish Kumar; Sahai, Rajiv Nandan; Indora, Jagmohan; Biswal, Upender Chand
The main cause of perforation of the gallbladder is cholecystitis with or without cholelithiasis. In old age, spontaneous perforation of gallbladder can be due to decrease in its blood supply, which can be due to atherosclerosis, focal vasospasm or localized vasculitis. Perforation of gallbladder is associated with high morbidity and mortality, if left untreated. Here we report a case of a 60-year-old male with perforation of gallbladder. PMID:27785327
Does gallbladder angle affect gallstone formation?
Sanal, Bekir; Korkmaz, Mehmet; Zeren, Sezgin; Can, Fatma; Elmali, Ferhan; Bayhan, Zulfu
Introduction Morphology of gallbladder varies considerably from person to person. We believe that one of the morphological variations of gallbladder is the "gallbladder angle". Gallbladder varies also in "angle", which, to the best of our knowledge, has never been investigated before. The purpose of this study was to investigate the impact of gallbladder angle on gallstone formation. Methods in this study, 1075 abdominal computed tomography (CT) images were retrospectively examined. Patients with completely normal gallbladders were selected. Among these patients, those with both abdominal ultrasound and blood tests were identified in the hospital records and included in the study. Based on the findings of the ultrasound scans, patients were divided into two groups as patients with gallstones and patients without gallstones. Following the measurement of gallbladder angles on the CT images, the groups were statistically evaluated. Results The gallbladder angle was smaller in patients with gallstones (49 ± 21 degrees and 53 ± 19 degrees) and the gallbladder with larger angle was 1.015 (1/0.985) times lower the risk of gallstone formation. However, these were not statistically significant (p>0,05). Conclusion A more vertically positioned gallbladder does not affect gallstone formation. However, a smaller gallbladder angle may facilitate gallstone formation in patients with the risk factors. Gallstones perhaps more easily and earlier develop in gallbladders with a smaller angle. PMID:27795762
A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature
Zhang, Chengsheng; Zhang, Wei; Mu, Dianbin; Shi, Xuetao; Zhao, Lei
An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL), whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL). Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients. PMID:27703378
Porcelain gallbladder: ultrasound and CT appearance
Kane, R.A.; Jacobs, R.; Katz, J.; Costello, P.
Nine patients with calcification of the gallbladder wall (porcelain gallbladder) were analyzed by ultrasound and the appearance correlated with the CT, radiographic, clinical, and surgical findings. Three distinct patterns were identified: (a) a hyperechoic similunar structure with acoustic shadowing posteriorly, simulating a stone-filled gallbladder devoid of bile, which was seen in 5 patients; (b) a biconvex, curvilinear echogenic structure with variable acoustic shadowing, seen in all 3 patients with carcinoma of the gallbladder; and (c) an irregular clump of echoes with posterior acoustic shadowing, seen in 1 patient. Potential pitfalls in the diagnosis of gallbladder calcification are presented, and the association between calcification and cancer is emphasized.
Gallbladder cancer: epidemiology and outcome
Hundal, Rajveer; Shaffer, Eldon A
Gallbladder cancer, though generally considered rare, is the most common malignancy of the biliary tract, accounting for 80%–95% of biliary tract cancers. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. Its carcinogenesis follows a progression through a metaplasia–dysplasia–carcinoma sequence. This comprehensive review focuses on and explores the risks, management, and outcomes for primary gallbladder carcinoma. Epidemiological studies have identified striking geographic and ethnic disparities – inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Age, female sex, congenital biliary tract anomalies, and a genetic predisposition represent important risk factors that are immutable. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Mortality rates closely follow incidence; those countries with the highest prevalence of gallstones experience the greatest mortality from gallbladder cancer. Vague symptoms often delay the diagnosis of gallbladder cancer, contributing to its overall progression and poor outcome. Surgery represents the only potential for cure. Some individuals are fortunate to be incidentally found to have gallbladder cancer at the time of cholecystectomy being performed for cholelithiasis. Such an early diagnosis is imperative as a late presentation connotes advanced staging, nodal involvement, and possible recurrence following attempted resection. Overall mean survival is a mere 6 months, while 5-year survival rate is only 5%. The dismal prognosis, in part, relates to the gallbladder lacking a serosal layer adjacent to the liver, enabling hepatic invasion and metastatic progression. Improved imaging modalities are helping to diagnose patients at an earlier
Gallbladder agenesis in a Chihuahua.
Kamishina, Hiroaki; Katayama, Masaaki; Okamura, Yasuhiko; Sasaki, Jun; Chiba, Satoshi; Goryo, Masanobu; Sato, Reeko; Yasuda, Jun
A 4-year-old neutered male Chihuahua was presented with a history of anorexia and vomiting. Continuous elevation of liver enzymes was found on repeated blood examinations and the dog was referred to us for further evaluation. The absence of gallbladder was suspected on ultrasonography. Exploratory laparotomy and retrograde cholangiography confirmed gallbladder agenesis and a possible hypoplasia of the right medial and lateral liver lobes. Histologically, proliferation of bile ductules associated with portal fibrosis and pseudolobular formation were apparent in the liver lobes.
Xanthogranulomatous cholecystitis mimicking gallbladder cancer.
Ewelukwa, Ofor; Ali, Omair; Akram, Salma
Xanthogranulomatous cholecystitis (XGC) is a benign, uncommon variant of chronic cholecystitis characterised by focal or diffuse destructive inflammatory process of the gallbladder (GB). Macroscopically, it appears like yellowish tumour-like masses in the wall of the GB. This article reports on a 74-year-old woman with XGC mimicking GB cancer.
Treatment Option Overview (Myelodysplastic/Myeloproliferative Neoplasms)
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General Information about Myelodysplastic/Myeloproliferative Neoplasms
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General Information about Chronic Myeloproliferative Neoplasms
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Treatment Options for Chronic Myeloproliferative Neoplasms
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Treatment Option Overview (Chronic Myeloproliferative Neoplasms)
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Treatment Options for Myelodysplastic/Myeloproliferative Neoplasms
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What's New in Gallbladder Cancer Research and Treatment?
... and Treatment? Gallbladder Cancer About Gallbladder Cancer What's New in Gallbladder Cancer Research and Treatment? Research into ... Chemotherapy and radiation therapy Researchers are looking at new ways of increasing the effectiveness of radiation therapy . ...
What Are the Key Statistics about Gallbladder Cancer?
... Cancer About Gallbladder Cancer What Are the Key Statistics About Gallbladder Cancer? The American Cancer Society's estimates ... advanced it is when it is found. For statistics on survival rates, see " Survival statistics for gallbladder ...
Gallbladder contractility in liver cirrhosis: comparative study in patients with and without gallbladder stones.
Acalovschi, Monica; Dumitrascu, Dan L; Nicoara, Cezar D
An increased prevalence of gallstones was demonstrated in patients with liver cirhosis, higher in the advanced stages of the disease. Some studies have found impaired emptying of the gallbladder in cirrhotic patients. Our aim here was to investigate gallbladder emptying in cirrhotic patients with and without gallstones to find out whether emptying is further impaired in the presence of gallstones. The study group comprised 24 patients with liver cirrhosis and gallstones, 8 in each Child class. The controls were represented by 18 cirrhotic patients without gallstones, 6 in each Child class. Fasting gallbladder volume was calculated by ultrasound using the ellipsoid formula. Gallbladder emptying was evaluated for 90 min after ingestion of a solid-liquid meal (14 g fat, 425 kcal), by assessing minimal residual volume, gallbladder ejection fraction, and area under emptying curve at 15-min intervals. Statistical analysis was performed using the two-tailed Students' t test and Pearson's correlation coefficient. In controls, gallbladder fasting and residual volumes increased with the severity of cirrhosis, but gallbladder emptying did not change significantly. In cirrhotics with gallstones, gallbladder emptying decreased in Child C compared with Child A class patients and, also, compared to Child C controls. The number or size of gallstones, as well as the thickness of the gallbladder wall, did not correlate with gallbladder emptying parameters. Gallbladder contractility is impaired in patients with liver cirrhosis and gallstones. Hypomotility is proportional to the severity of liver disease. Gallbladder hypomotility might contribute to the increased gallstone formation in patients with advanced cirrhosis.
[Mucoprotein secretion in calculous gallbladder].
Fernández Lobato, R; Ortega, L; Balibrea, J L; Torres, A J; García-Calvo, M; Alvarez Sánchez, J A
Secretion of mucoproteins or mucine (MP) have been studied as possible markers in several pathological conditions of the digestive tract, such us colonic polyposis or gastric dysplasia. In the gallbladder (VB) it has been established that form the core of crystalization for the calculi. A study in 100 gallbladders have been made based on the utility of the analysis of the qualitative and quantitative modifications of MP in lithogenesis. It was been determined by histochemical techniques the three main types of MP (neutral, low and high sulphated acid) to evaluate the alterations in the process of lithiasis. Results show a high production of the MP in VB with lithiasis, presenting in 97% a mixed composition of MP (48.9% of 2 types, and 3 types in 46%), without a predominating type in this pathology.
Gallbladder metastasis: spectrum of imaging findings.
Barretta, Maria Luisa; Catalano, Orlando; Setola, Sergio Venanzio; Granata, Vincenza; Marone, Ugo; D'Errico Gallipoli, Adolfo
The objective of this study is to report the diagnostic features of hematogenous gallbladder metastasis using various imaging modalities. We carried out a single-center retrospective analysis of 13 patients with gallbladder metastasis. The primary malignancy was cutaneous melanoma (11 cases), hepatocellular carcinoma (1 case), and non-Hodgkin lymphoma (1 case). All patients underwent sonography (US), with color-power-Doppler assessment in 11 cases. Contrast-enhanced US (CEUS) was performed in 8 patients, MDCT in 8, and MR imaging in 1. Four subjects studied by whole-body PET. The gallbladder lesions were first detected with US in 9 cases and with MDCT in 3 cases. The remaining patient was investigated because of hepatic fluorodeoxyglucose uptake at PET; CEUS failed to detect any liver metastasis in this subject but identified a gallbladder lesion. Typical findings included multiplicity of gallbladder vegetations, broad base, limited mural thickening, presence of contrast enhancement, absence of gallstones and gallbladder bed infiltration, presence of combined lesions within other organs. Only two patients presented an isolated location in the gallbladder and were successfully treated with surgery. Gallbladder metastasis is a rare but possible occurrence. Knowledge of the typical imaging features and careful evaluation of the gallbladder may avoid an incorrect or false negative diagnosis.
Endoscopic Gallbladder Drainage for Acute Cholecystitis
Widmer, Jessica; Alvarez, Paloma; Sharaiha, Reem Z.; Gossain, Sonia; Kedia, Prashant; Sarkaria, Savreet; Sethi, Amrita; Turner, Brian G.; Millman, Jennifer; Lieberman, Michael; Nandakumar, Govind; Umrania, Hiren; Gaidhane, Monica
Background/Aims Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage. Methods Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued. Results During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%). Conclusions Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities. PMID:26473125
Design and application of a new series of gallbladder endoscopes that facilitate gallstone removal without gallbladder excision
NASA Astrophysics Data System (ADS)
Chiao, Tie; Huang, Wan-Chao; Luo, Xiao-Bing; Zhang, Yang-De
In recent years, some Chinese doctors have proposed a new concept, gallstone removal without gallbladder excision, along with transition of the medical model. As there is no specialized endoscope for gallstone removal without gallbladder excision, we designed and produced a new series of gallbladder endoscopes and accessories that have already been given a Chinese invention patent (No. ZL200810199041.2). The design of these gallbladder endoscopes was based on the anatomy and physiology of the gallbladder, characteristics of gallbladder disease, ergonomics, and industrial design. This series of gallbladder endoscopes underwent clinical trials in two hospitals appointed by the State Administration of Traditional Chinese Medicine. The clinical trials showed that surgeries of gallstones, gallbladder polyps, and cystic duct calculus could be smoothly performed with these products. In summary, this series of gallbladder endoscopes is safe, reliable, and effective for gallstone removal without gallbladder excision. This note comprehensively introduces the research and design of this series of gallbladder endoscopes.
Promotion of gallbladder emptying by intravenous aminoacids.
Zoli, G; Ballinger, A; Healy, J; O'Donnell, L J; Clark, M; Farthing, M J
Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.
BMS-247550 in Treating Patients With Liver or Gallbladder Cancer
Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
Localized IgG4-related Cholecystitis Mimicking Gallbladder Cancer.
Inoue, Tadahisa; Okumura, Fumihiro; Mizushima, Takashi; Nishie, Hirotada; Iwasaki, Hiroyasu; Anbe, Kaiki; Ozeki, Takanori; Kachi, Kenta; Fukusada, Shigeki; Suzuki, Yuta; Watanabe, Kazuko; Sano, Hitoshi
We encountered a case of localized IgG4-cholecystitis mimicking gallbladder cancer with focal/segmental type1 autoimmune pancreatitis (AIP). In this case, we were unable to exclude a diagnosis of gallbladder cancer and thus performed radical cholecystectomy. Type1 AIP is often associated with gallbladder lesions, accompanied by generally diffuse, circumferential thickening of the gallbladder wall. Although localized IgG4-related cholecystitis is extremely rare, differentiating this condition from gallbladder cancer is often very difficult.
Unusual presentation of gallbladder perforation
Jayasinghe, G.; Adam, J.; Abdul-Aal, Y.
Introduction Gall bladder perforation is associated with high mortality rates and therefore must be recognised and managed promptly. We present an unusual presentation of spontaneous gall bladder perforation. Case presentation An elderly lady with multiple medical co-morbidities was admitted with sepsis following a fall. Initial assessment lead to a diagnosis of pneumonia, however a rapidly expanding right flank mass was incidentally noted during routine nursing care. Imaging studies were inconclusive, however incision and drainage of the mass revealed bile stained pus draining cutaneously from an acutely inflamed gallbladder. The patient made a good recovery following surgery, and was discharged with outpatient follow-up. Discussion Despite focussed post-hoc history taking she denied any prodromal symptoms of cholecystitis. In addition to reporting an unusual cause for a common presentation, we highlight the importance of a full body examination in the context of sepsis, regardless of whether the source has been identified. In addition, we advocate that surgical intervention in sepsis should not be delayed by imaging in cases where an abscess is suspected. Conclusions Percutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis, and may present in a wide variety of locations. Therefore it is imperative to conduct a full body inspection in the septic patient, even when a source has been identified. PMID:26686488
Single Incision Laparoscopic Cholecystectomy for Gallbladder Duplication
Kabul Gürbulak, Esin; Özşahin, Hamdi; Düzköylü, Yiğit; Akgün, Ismail Ethem; Battal, Muharrem; Gürbulak, Bünyamin
Duplication of the gallbladder is a rare congenital anomaly of the gallbladder, with an estimated prevalence of 1–3 per 3800 individuals. Unless properly diagnosed preoperatively, it can lead to biliary tract injuries and postoperative complications which may require reoperative surgeries. While previously reported cases have been treated with conventional laparoscopic cholecystectomy (LC), treatment with single incision laparoscopic surgery (SILS) has not been reported yet. We herein present the case of a 58-year-old female with gallbladder duplication who was successfully treated with SILS cholecystectomy. PMID:26266074
Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma
Extrahepatic Bile Duct Adenocarcinoma; Gallbladder Adenocarcinoma; Gallbladder Adenocarcinoma With Squamous Metaplasia; Hilar Cholangiocarcinoma; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Undifferentiated Gallbladder Carcinoma; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma
Metastatic Cutaneous Melanoma of the Gallbladder
Basnyat, Soney; Basu, Aparna; Mehta, Vivek R.
Metastatic melanoma is an aggressive disease that can spread to many organs of the body. In rare cases, it can spread to the gallbladder causing secondary lesions, yet presenting with little to no symptoms. Therefore, most cases of metastatic melanoma lesions to the gallbladder go undiagnosed. Here, we present the case of a 41-year-old male with a four-month history of melanoma of the face, with a postresection status, who presented with right upper quadrant abdominal pain. Doppler ultrasound and computed tomography confirmed the presence of a mass on the gallbladder. Laparoscopic excision along with liver wedge resection was performed. Pathology staining revealed the presence of a malignant metastatic melanoma lesion of the gallbladder. PMID:28251000
Gallbladder Cleanse: A "Natural" Remedy for Gallstones?
... cleanse involves eating or drinking a combination of olive oil, herbs and some type of fruit juice ... them in stool. The large, repeated doses of olive oil in gallbladder cleanse preparations do have a ...
Gallbladder Polyps: Can They Be Cancerous?
... these polyps, your doctor may suggest follow-up examinations to look for changes that may be an indication of cancer. This can be done using standard abdominal ultrasound or endoscopic ultrasound. Gallbladder polyps larger ...
Parastomal herniation of the gallbladder.
Garcia, R M; Brody, F; Miller, J; Ponsky, T A
Parastomal hernias can occur in up to 31% of patients following an enterostomy (Cheung in Aust N Z J Surg 65:808-811, 1995). This type of hernia develops through an intentional fascial defect. Commonly, most parastomal hernias involve a reducible segment of omentum, small bowel, or colon. Typically, these hernias are asymptomatic and associated rarely with strangulation or obstruction. Patient preference and clinical scenario may dictate management of these hernias. Non-operative management of parastomal hernias includes abdominal binders and enterostomy belts. Operative management includes a host of options including mesh repair, a new stoma site, or revision. This paper documents the first reported case of a parastomal hernia involving the gallbladder. Optimal technique and site placement of a stoma are also discussed.
Impaired Gallbladder Motility and Increased Gallbladder Wall Thickness in Patients with Nonalcoholic Fatty Liver Disease
Colak, Yasar; Bozbey, Gulcin; Erim, Tolga; Caklili, Ozge Telci; Ulasoglu, Celal; Senates, Ebubekir; Mutlu, Hasan Huseyin; Mesci, Banu; Doğan, Mehmet Sait; Tasan, Guralp; Enc, Feruze Yilmaz; Tuncer, Ilyas
Background/Aims Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD. Methods An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography. Results Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls. Conclusions Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD. PMID:26932908
Determinants of gallbladder kinetics in obesity.
Mathus-Vliegen, E M H; Van Ierland-Van Leeuwen, M L; Terpstra, A
Obese subjects are at risk of developing gallstones both by being overweight and by reducing their body weight. The aim of the present study was to investigate factors related to disturbances in gallbladder emptying measured by ultrasound. Detailed information about weight loss attempts, age at onset of obesity, parity, presence of menopause, use of contraceptive or hormonal replacement drugs, and phase of menstrual cycle was obtained. Smoking habits, alcohol use, dietary intake, and physical activity were recorded. Body composition and fat distribution were assessed by anthropometry. Blood samples were taken for CCK, lipids, glucose, and insulin. Mean (SD) fasting gallbladder volume was 30.0 (12.6) ml. The residual volume was 12.5 (9.8) ml 90 min after a test meal. CCK levels increased from a basal 1.64 (0.8) pM to a peak value of 2.9 (1.0) pM. Fasting gallbladder volumes were closely related to residual and ejection volumes. Body weight and fasting insulin levels explained 35.2% of the variance in fasting volume, lean body mass and insulin explained 28.1% of the residual volume, and waist circumference 23.6% of the ejection volume. None of the other factors were related to gallbladder emptying. Subjects with the largest fasting gallbladders had the largest residual and least emptying gallbladders, scored the highest in every aspect of body size, composition, and fat distribution, and also had the highest insulin levels. Body weight, lean body mass, central fat distribution, and insulin levels were the main determinants of gallbladder kinetics. Fasting and residual gallbladder volumes were closely related and both determined by obesity and its metabolic complication of hyperinsulinemia.
A new exploration for gallbladder polyps: gallbladder polypectomy by endolap technique.
Wang, JingMin; Tan, YuYan; Zhao, Gang; Wang, Dong; Ji, ZhenLing
Abstract Gallbladder polyps are most commonly treated with cholecystectomy, which is associated with various complications. For benign disease, preserving the gallbladder is preferable. Since 1994, we have been exploring percutaneous polypectomy and have recently developed an improved new technique. This study reports a new endoscopic-laparoscopic (Endolap) technique for the removal of polyps and the preservation of the gallbladder. Nine Chinese mini-pigs were used to observe mucosal regeneration. Microwaves of 50-70 mA for 9 seconds were safe, and the gallbladder mucosa of pigs recovered to nearly normal 2 weeks later. In the clinical cases, 60 patients with gallbladder polyps were studied. With the patient under general anesthesia, each polyp stem was coagulated, and then the polyp was removed. All procedures were successful at between 60 and 135 minutes. The success rate was 93.33% (56/60). A retrospective analysis was conducted to assess the recovery of gallbladder function. All patients were followed up and symptom-free, without recurrence of the polyps; 3 months after the operation, the volume and contraction of the gallbladder recovered to preoperative levels. Thus the Endolap technique is reliable for removing benign gallbladder polyps and is applicable to a wider range of clinical situations than percutaneous polypectomy.
The frequency and influence of gallbladder varices on gallbladder functions in patients with portal hypertension.
Chawla, A; Dewan, R; Sarin, S K
Gallbladder varices have been reported in patients with portal hypertension. The exact frequency and significance of these collaterals in patients with cirrhotic and noncirrhotic portal hypertension is not known. One hundred and two patients with portal hypertension [38 with cirrhosis, 29 with noncirrhotic portal fibrosis (NCPF) and 35 with extrahepatic portal vein obstruction (EHPVO)] and 25 healthy controls were studied. Gallbladder varices were seen at ultrasound as tortuous, dilated vessels in the wall or in the bed of the gallbladder. In 35 patients (19 patients with and 16 without gallbladder varices) and in 10 healthy controls, gallbladder functions were studied by determining fasting volume (FV) and then residual volume (RV) every 10 min over 1 h after giving a liquid meal of 420 k.cal. Ejection fraction (EF) was computed as a percentage by the formula: FV--RV/FV x 100. Twenty four (24%) patients had gallbladder varices: Five (13%) with cirrhosis, seven (24%) with NCPF, and 12 (34%) with EHPVO. FV in EHPVO patients was seen significantly more than in cirrhotics (31.6 +/- 15.4 vs 19.3 +/- 6.0 ml, p < 0.05). The RV and EF were not different in the three groups of patients compared with the controls. The EF was similar in patients with or without gallbladder varices (63.3 +/- 10.2% vs 64.6 +/- 10.4%). Gallbladder varices are often seen in portal hypertension, more often in EHPVO patients, and these collaterals cause some gallbladder stasis but do not impede gallbladder function and hence seem unlikely to contribute to gallstone formation.
Intraductal papillary neoplasm originating from an anomalous bile duct.
Maki, Harufumi; Aoki, Taku; Ishizawa, Takeaki; Tanaka, Mariko; Sakatani, Takashi; Beck, Yoshifumi; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Kokudo, Norihiro
An 82-year-old woman who had been suffering from repeated obstructive jaundice for 7 years was referred to our hospital. Although endoscopic aspiration of the mucin in the common bile duct had been temporally effective, origin of the mucin production had not been detectable. The patient thus had been forced to be on long-term follow-up without curative resection. Endoscopic retrograde cholangioscopy on admission revealed massive mucin in the common bile duct. In addition, an anomalous bile duct located proximal to the gallbladder was identified. Since the lumen of the anomalous duct was irregular and the rest of biliary tree was completely free of suspicious lesions, the anomalous duct was judged to be the primary site. Surgical resection of the segment 4 and 5 of the liver combined with the extrahepatic biliary tract was performed. Pathological diagnosis was compatible to intraductal papillary neoplasm with high-grade intraepithelial dysplasia of the anomalous bile duct. The patient has been free from the disease for 6.5 years after resection. This is the first case of intraductal papillary neoplasm derived from an anomalous bile duct, which was resected after long-term conservative treatment. The present case suggested the slow growing character of natural history of the neoplasm.
Gallbladder carcinoma: Prognostic factors and therapeutic options.
Goetze, Thorsten Oliver
The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas
Gallbladder carcinoma: Prognostic factors and therapeutic options
Goetze, Thorsten Oliver
The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2
Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer
Stinton, Laura M.
Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps. PMID:22570746
Gallbladder cancer: South American experience.
Arroyo, Gerardo F; Gentile, Alberto; Parada, Luis A
Large differences in terms of incidence and mortality due to gallbladder cancer (GBC) have been reported worldwide. Moreover, it seems that GBC has unique characteristics in South America. We surveyed the literature looking for information about the epidemiology, basic and translational research, and clinical trials performed in South America in order to critically analyze the magnitude of this health problem in the region. Compared to other geographic areas, age-standardized mortality rates (ASMR) for GBC in women are very high, particularly in many western areas of South America. Genetic, as well as dietary and environmental factors likely contribute to the pathogenesis of this disease in the area. Compared to other regions the profile of abnormalities of key genes such as KRAS and TP53 in GBC seems to slightly differ in South America, while the clinical behavior appears to be similar with a median overall survival (OS) of 6.5 to 8 months in advanced GBC. In contrast to Europe and USA, prophylactic cholecystectomy is a common practice in western areas of South America. GBC particularly affects women in South America, and represents a significant public health problem. It appears to have peculiarities that pose an urgent need for additional research aimed to discover risk factors, molecular events associated with its development and new treatment options for this lethal disease.
Bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge.
Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime
OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge. ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group). PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group. RESULTS Concentrations of most bile acids in the GBM group were significantly lower than those in the control and m-BS groups. Compositional ratio of taurodeoxycholic acid, which is 1 of 3 major bile acids in dogs, was significantly lower in the GBM and i-BS groups, compared with ratios for the control and m-BS groups. The compositional ratio of taurocholic acid was significantly higher and that of taurochenodeoxycholic acid significantly lower in the i-BS group than in the control group. CONCLUSIONS AND CLINICAL RELEVANCE In this study, concentrations and fractions of bile acids in gallbladder contents were significantly different in dogs with gallbladder mucocele or immobile biliary sludge, compared with results for healthy control dogs. Studies are needed to determine whether changes in bile acid composition are primary or secondary events of gallbladder abnormalities.
Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia.
Mawe, G M; Talmage, E K; Cornbrooks, E B; Gokin, A P; Zhang, L; Jennings, L J
The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin
Molecular Biology of Gallbladder Cancer: Potential Clinical Implications
Andrén-Sandberg, Åke
Gallbladder cancer (GBC) is a common malignancy of the biliary tract and involves the changes in multiple oncogenes and multiple genetic genes. Since over the past decade there has been an advance in the knowledge of the genetic basis of cancer, mainly as a result of the rapid progression of molecular technology; however, conventional therapeutic approaches have not had much impact on the course of this aggressive neoplasm. Knowledge of the molecular biology of GBC is rapidly growing. Genetic alterations in GBC include adenosine triphosphate-binding cassette transporter ABCG8, membrane-bound enzyme ADAM-17 of multi-functional gene family, and other genes including p53, COX2, XPC, and RASSF1A. The advances in molecular biology have potential implications for the detection of this disease, using Synuclein-gamma, Syndecan-1, glycoprotein 72 (TAG-72), tumor endothelial marker 8 protein (TEM8) and TNF-alpha. The use of these molecular diagnostic methods is of clinical importance for the gene replacement therapy, genetic prodrug activation therapy, and antisense immunology technology for the treatment of malignancy. The author reviewed recent publications on PubMed, and summarized molecular biology of GBC, with an emphasis on features of potential clinical implications for diagnosis and management. PMID:23112962
Arachidonate metabolism in bovine gallbladder muscle
Nakano, M.; Hidaka, T.; Ueta, T.; Ogura, R.
Incubation of (1-/sup 14/C)arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of (1-/sup 14/C)PGH2 was virtually identical to that of (1-/sup 14/C)AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.
Agenesis of the Gallbladder in Monozygotic Twin Sisters
Hoshi, Koki; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Igarashi, Ryo; Sato, Ai; Maki, Takumi
Agenesis of the gallbladder, a rare anomaly, is generally regarded as an organogenic failure. Several reports suggest that this congenital defect is inherited but that supposition remains controversial. We described agenesis of the gallbladder in identical twins. A 21-year-old female presented with a history of acute pain in the epigastrium and right hypochondrium. Various imaging modalities showed "gallbladder agenesis." Moreover, her older identical twin sister had also no visualized gallbladder in imaging modalities. This case report strongly suggested that agenesis of the gallbladder would be caused by a genetic abnormality. PMID:26925274
Agenesis of the Gallbladder in Monozygotic Twin Sisters.
Hoshi, Koki; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Igarashi, Ryo; Sato, Ai; Maki, Takumi
Agenesis of the gallbladder, a rare anomaly, is generally regarded as an organogenic failure. Several reports suggest that this congenital defect is inherited but that supposition remains controversial. We described agenesis of the gallbladder in identical twins. A 21-year-old female presented with a history of acute pain in the epigastrium and right hypochondrium. Various imaging modalities showed "gallbladder agenesis." Moreover, her older identical twin sister had also no visualized gallbladder in imaging modalities. This case report strongly suggested that agenesis of the gallbladder would be caused by a genetic abnormality.
In vitro modeling of gallbladder-associated Salmonella spp. colonization.
Gonzalez-Escobedo, Geoffrey; Gunn, John S
The host-pathogen interactions occurring in the gallbladder during Salmonella Typhi colonization contribute to typhoid fever pathogenesis during the acute and chronic stages of disease. The gallbladder is the primary reservoir during chronic typhoid carriage. In this organ, Salmonella encounters host-barriers including bile, immunoglobulins, and mucus. However, the bacterium possesses mechanisms to resist and persist in this environment, in part by its ability to attach to and invade into the gallbladder epithelium. Such persistence in the gallbladder epithelium contributes to chronic carriage. In addition, patients harboring gallstones in their gallbladders have increased risk of becoming carriers because these abnormalities serve as a substrate for Salmonella biofilm formation. Our laboratory has studied the Salmonella interactions in this specific environment by developing in vitro methods that closely mimic the gallbladder and gallstones niches. These methods are reproducible and provide a platform for future studies of acute and chronic bacterial infections in the gallbladder.
Occupation and lymphoid neoplasms.
La Vecchia, C.; Negri, E.; D'Avanzo, B.; Franceschi, S.
The relationship between occupation and exposure to a number of occupational agents and lymphoid neoplasms was investigated in a case-control study of 69 cases of Hodgkin's disease, 153 non-Hodgkin's lymphomas, 110 multiple myelomas and 396 controls admitted for acute diseases to a network of teaching and general hospitals in the greater Milan area. Among the cases, there was a significant excess of individuals ever occupied in agriculture and food processing: the multivariate relative risks (RR) were 2.1 (95% confidence interval, CI = 1.0-3.8) for Hodgkin's disease, 1.9 (95% CI = 1.2-3.0) for non-Hodgkin's lymphomas and 2.0 (95% CI = 1.1-3.5) for multiple myeloma. Significant trends for duration of exposure to herbicides were observed for lymphomas, but the association was stronger for overall occupation in agriculture than with the specific question of herbicide use. History of occupation in the chemical industry was more frequent among Hodgkin's disease (RR = 4.3, 95% CI = 1.4-10.2), and a significant trend in risk was observed between duration of exposure to benzene and other solvents and multiple myeloma. No significant relation was found between any of the lymphoid neoplasms considered and rubber, dye, painting, printing, tanning leather, photography, pharmaceuticals, wood, coal/gas and nuclear industries. PMID:2789947
Diagnosis and Management of Gallbladder Cancer
Andrén-Sandberg, Åke
Gallbladder cancer (GBC) is a rather uncommon disease, but at the time when it gives symptoms it has usually reached no longer curable stage. Therefore, all attempts must be made to make the diagnosis earlier to have better opportunity for cure. The author searched PubMed, and reviewed literatures on diagnoses and treatment of GBC. PMID:22866265
[Leiomyosarcoma of the gallbladder: a clinical case].
Tocchi, A; Codacci-Pisanelli, M; Costa, G; Lepre, L; Agostini, N; Maggiolini, F
A case of primary leiomyosarcoma of the gallbladder is reported together with a review of the literature. The nonspecific clinical picture of the disease and the consequent high frequency of misdiagnosis are stressed. Cholecystectomy combined with chemotherapy and radiotherapy is the treatment of choice suggested.
Necrotizing fasciitis following gall-bladder perforation.
Rehman, A; Walker, M; Kubba, H; Jayatunga, A P
Necrotizing fasciitis continues to carry a very high mortality and prolonged morbidity. Gallstones have previously not been reported as a cause of this condition. We report a patient who presented with gallbladder perforation leading to necrotizing fasciitis of the anterior abdominal wall. The only organism isolated was Escherichia Coli, cultured from necrotic issue.
The inflammatory inception of gallbladder cancer.
Espinoza, Jaime A; Bizama, Carolina; García, Patricia; Ferreccio, Catterina; Javle, Milind; Miquel, Juan F; Koshiol, Jill; Roa, Juan C
Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia-dysplasia-carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.
ACTH-secreting 'apudoma' of gallbladder.
Spence, R W; Burns-Cox, C J
The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side. Images Fig 1 Fig 2 PMID:168130
Electrogenic bicarbonate secretion by prairie dog gallbladder.
Moser, A James; Gangopadhyay, A; Bradbury, N A; Peters, K W; Frizzell, R A; Bridges, R J
Pathological rates of gallbladder salt and water transport may promote the formation of cholesterol gallstones. Because prairie dogs are widely used as a model of this event, we characterized gallbladder ion transport in animals fed control chow by using electrophysiology, ion substitution, pharmacology, isotopic fluxes, impedance analysis, and molecular biology. In contrast to the electroneutral properties of rabbit and Necturus gallbladders, prairie dog gallbladders generated significant short-circuit current (I(sc); 171 +/- 21 microA/cm(2)) and lumen-negative potential difference (-10.1 +/- 1.2 mV) under basal conditions. Unidirectional radioisotopic fluxes demonstrated electroneutral NaCl absorption, whereas the residual net ion flux corresponded to I(sc). In response to 2 microM forskolin, I(sc) exceeded 270 microA/cm(2), and impedance estimates of the apical membrane resistance decreased from 200 Omega.cm(2) to 13 Omega.cm(2). The forskolin-induced I(sc) was dependent on extracellular HCO(3)(-) and was blocked by serosal 4,4'-dinitrostilben-2,2'-disulfonic acid (DNDS) and acetazolamide, whereas serosal bumetanide and Cl(-) ion substitution had little effect. Serosal trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chroman and Ba(2+) reduced I(sc), consistent with the inhibition of cAMP-dependent K(+) channels. Immunoprecipitation and confocal microscopy localized cystic fibrosis transmembrane conductance regulator protein (CFTR) to the apical membrane and subapical vesicles. Consistent with serosal DNDS sensitivity, pancreatic sodium-bicarbonate cotransporter protein pNBC1 expression was localized to the basolateral membrane. We conclude that prairie dog gallbladders secrete bicarbonate through cAMP-dependent apical CFTR anion channels. Basolateral HCO(3)(-) entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K(+) channel activation.
MUC Expression in Gallbladder Epithelial Tissues in Cholesterol-Associated Gallbladder Disease
Yoo, Kyo-Sang; Choi, Ho Soon; Jun, Dae Won; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Lee, Kyeong Geun; Paik, Seung Sam; Kim, Yong Seok; Lee, Jin
Background/Aims Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol-associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. Methods The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. Results MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. Conclusions The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression. PMID:27563024
Optimal block sampling of routine, non-tumorous gallbladders.
Wong, Newton Acs
Gallbladders are common specimens in routine histopathological practice and there are, at least in the United Kingdom and Australia, national guidance on how to sample gallbladders without macroscopically-evident, focal lesions/tumours (hereafter referred to as non-tumorous gallbladders).(1) Nonetheless, this author has seen considerable variation in the numbers of blocks used and the parts of the gallbladder sampled, even within one histopathology department. The recently re-issued 'Tissue pathways for gastrointestinal and pancreatobiliary pathology' from the Royal College of Pathologists (RCPath), first recommends sampling of the cystic duct margin and "at least one section each of neck, body and any focal lesion".(1) This recommendation is referenced by a textbook chapter which itself proposes that "cross-sections of the gallbladder fundus and lateral wall should be submitted, along with the sections from the neck of the gallbladder and cystic duct, including its margin".(2) This article is protected by copyright. All rights reserved.
Emptying the gallbladder prior to intravenous cholangiography: effect on gallbladder visualization.
Martinez, C R; Fara, J W; Donner, M W
Experiments were done to test the hypothesis that emptying the gallbladder prior to intravenous cholangiography (IVC) would result in earler and better opacification of the gallbladder. Five dogs were studied on two separate days in a crossover experiment. Each dog had a standard IVC (15-minute infusion of meglumine iodipamide) 2.5 cc/kg of following a 14-16-hour fasting period. On one of the days, 0.3 mcg/kg of Ceruletide was intramuscularly administered to each dog 30 to 45 minutes prior to the iodipamide infusion. Films obtained at the end of infusion and at 20, 40, 60, and 90 minutes were evaluated independently by three radiologists. The results indicate that pretreatment with Ceruletide produces a significant (p less than 0.05) improvement in the quality of gallbladder opacification during the first 90 minutes following iodipamide infusion. We conclude that earlier and better opacification of the gallbladder during IVC can be obtained by prior emptying of the gallbladder with a cholecystokinetic agent.
Gallbladder tuberculosis camouflaging as gallbladder cancer – case series and review focussing on treatment
Krishnamurthy, Gautham; Singh, Harjeet; Rajendran, Jayapal; Sharma, Vishal; Yadav, Thakur Deen; Gaspar, Balan Louis; Vasishta, Rakesh Kumar; Singh, Rajinder
Introduction: Gallbladder tuberculosis, in an endemic region, is a common infectious etiology affecting a rare organ. The high prevalence of carcinoma gallbladder in the endemic regions of tuberculosis, like India, poses diagnostic dilemma. Case series: We are reporting three cases of gallbladder tuberculosis mimicking carcinoma gallbladder of which the first two cases were operated with a presumptive diagnosis of malignancy. The third case presented to us after laparoscopic cholecystectomy elsewhere and on evaluation was found to have disseminated tuberculosis. Discussion: The lack of pathognomonic clinical and radiological characters results in histological surprise of gallbladder tuberculosis following surgery performed for other indications like malignancy. In preoperatively diagnosed patients medical management plays pivotal role in management. Surgery is required in symptomatic patients. On the other hand, histologically proven cases following surgical resection require antitubercular therapy. Conclusion: Previous history of tuberculosis or concomitant tuberculosis at other sites may provide clue to the diagnosis of biliary tuberculosis. Antitubercular treatment after surgery plays an important role in preventing further dissemination. PMID:28386408
Gallbladder perforation in a patient on steroid therapy.
Andrabi, Syed Imran; Ahmad, Jawad; Rathore, Munir A; El-Hakeem, Ahmed A
Gallbladder perforation is a serious clinical condition. A definitive diagnosis is contentious before surgery. We discuss a case where a young patient with Crohn's disease taking oral steroids presented with an acute abdomen. CT scan demonstrated a perforated gallbladder without evidence of gallstones. The patient underwent an emergency cholecystectomy and peritoneal lavage. The history and clinical findings of this patient are reviewed to highlight perforation of the gallbladder in relation to steroid therapy.
Isolated gallbladder injury in a case of blunt abdominal trauma.
Birn, Jeffrey; Jung, Melissa; Dearing, Mark
The diagnosis of blunt injury to the gallbladder may constitute a significant challenge to the diagnostician. There is often a delay in presentation with non-specific clinical symptoms. In the absence of reliable clinical symptoms, diagnostic imaging becomes an invaluable tool in the rapid identification of gallbladder injury. We present a case of isolated gallbladder injury following blunt abdominal trauma which was diagnosed by computed tomography and subsequently confirmed by cholecystectomy.
Megalin and cubilin in the human gallbladder epithelium.
Tsaroucha, Alexandra K; Chatzaki, Ekaterini; Lambropoulou, Maria; Despoudi, Kaliopi; Laftsidis, Prodromos; Charsou, Chara; Polychronidis, Alexandros; Papadopoulos, Nikolaos; Simopoulos, Constantinos E
Although the role of cholesterol absorption by the gallbladder epithelium in gallstone formation is well established, the exact process is poorly understood. Potential candidates for regulation of transepithelial cholesterol transport are suggested to be two large membrane multiple ligand receptors, megalin and cubilin. We studied the expression of these two proteins in both acalculous and calculous human gallbladder epithelia. Adult human gallbladder tissues were received from 21 patients (9 men, 12 women) who had undergone cholecystectomy. The patients were divided into two groups: group A (calculous gallbladder group; 5 men, 6 women; mean age 64.4 +/- 11.1 years) with cholelithiasis, and group B (acalculous gallbladder group; 4 men, 6 women; mean age 55.3 +/- 16.1 years). In the gallbladder tissues megalin and cubilin expression was studied by immunohistochemistry and conventional RT-PCR, and gene expression levels were estimated by real-time RT-PCR. Both megalin and cubilin gene transcripts were found in total RNA preparations from acalculous gallbladder. In contrast, in preparations from calculous gallbladder, none or only one of the proteins was detected. Immunoreactive proteins were detected in the simple columnar acalculous gallbladder epithelium but not in the calculous gallbladder epithelium. Our results show different expression patterns of the two proteins in calculous gallbladders and acalculous gallbladders. In the latter both proteins are expressed, suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis. In other words, the presence of both proteins may be essential for the prevention of stone formation.
Response of BRCA1-mutated gallbladder cancer to olaparib: A case report
Xie, Yuan; Jiang, Yan; Yang, Xiao-Bo; Wang, An-Qiang; Zheng, Yong-Chang; Wan, Xue-Shuai; Sang, Xin-Ting; Wang, Kai; Zhang, Da-Dong; Xu, Jia-Jia; Li, Fu-Gen; Zhao, Hai-Tao
Gallbladder cancer (GBC), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. The late diagnosis and abysmal prognosis present challenges to treatment. The overall 5-year survival rate for metastatic GBC patients is extremely low. BRCA1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European Commission for the treatment of ovarian cancer with any BRCA1/2 mutations. The first case of a BRCA1-mutated GBC patient who responded to olaparib treatment is reported here. PMID:28028375
Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro
Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C
Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells. PMID:23593935
Adenomyomatosis of the gallbladder--case report.
Lalović, Nenad; Cvijanović, Radovan; Vladicić, Nikolina Dukić; Marić, Radmil; Jokanović, Dragana; Skipina, Danijela Batinić
Adenomyomatosis of the gallbladder is a benign, mostly asymptomatic condition of an unknown aetiology. Hyperplastic changes in the gallbladder wall cause an overgrowth of the mucosa, thickening of the muscular wall, and formation of intramural diverticula or sinus tracts termed Rokitansky-Aschoff sinuses. Adenomyomatosis is divided on general, segmental and localised. Ultrasound examination, computerized tomography and magnetic resonance are used in diagnostic procedure. The importance of the disease lies in the fact that it can cause recurrent right upper quadrant pain so it must be concerned in resolving pain cause. This paper was aimed at explaining the aetiology of the disease, its clinical manifestation, making diagnosis and therapy in order to make its diagnosis and treatment possible.
Gallbladder carcinoma presenting as exfoliative dermatitis (erythroderma).
Kameyama, Hitoshi; Shirai, Yoshio; Date, Kazutoshi; Kuwabara, Akifumi; Kurosaki, Ryo; Hatakeyama, Katsuyoshi
Although exfoliative dermatitis (erythroderma) secondary to malignancy is commonly associated with lymphomas or leukemias, coincident gastrointestinal (GI) malignancy and erythroderma is rare. The authors recently encountered a patient with gallbladder carcinoma presenting as erythroderma. A 77-yr-old Japanese man presented with a 3-mo history of erythematous eruptions with pruritus over almost the entire body. After confirming the diagnosis of erythroderma, asymptomatic gallbladder carcinoma was found. Further investigations detected no malignancies in other organs. An extended cholecystectomy was performed. Histologic examination of resected specimens revealed poorly differentiated adenocarcinoma with negative resection margins. The eruptions with pruritus resolved within 1 wk after the operation. This is the first report, to our knowledge, of coincident biliary malignancy and erythroderma. The experience of the current patient suggests that erythroderma secondary to GI malignancy may resolve spontaneously after curative resection of the tumor.
Residual gallbladder stones after cholecystectomy: A literature review
Chowbey, Pradeep; Sharma, Anil; Goswami, Amit; Afaque, Yusuf; Najma, Khoobsurat; Baijal, Manish; Soni, Vandana; Khullar, Rajesh
BACKGROUND: Incomplete gallbladder removal following open and laparoscopic techniques leads to residual gallbladder stones. The commonest presentation is abdominal pain, dyspepsia and jaundice. We reviewed the literature to report diagnostic modalities, management options and outcomes in patients with residual gallbladder stones after cholecystectomy. MATERIALS AND METHODS: Medline, Google and Cochrane library between 1993 and 2013 were reviewed using search terms residual gallstones, post-cholecystectomy syndrome, retained gallbladder stones, gallbladder remnant, cystic duct remnant and subtotal cholecystectomy. Bibliographical references from selected articles were also analyzed. The parameters that were assessed include demographics, time of detection, clinical presentation, mode of diagnosis, nature of intervention, site of stone, surgical findings, procedure performed, complete stone clearance, sequelae and follow-up. RESULTS: Out of 83 articles that were retrieved between 1993 and 2013, 22 met the inclusion criteria. In most series, primary diagnosis was established by ultrasound/computed tomography scan. Localization of calculi and delineation of biliary tract was performed using magnetic resonance imaging/magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography. In few series, diagnosis was established by endoscopic ultrasound, intraoperative cholangiogram and percutaneous transhepatic cholangiography. Laparoscopic surgery, endoscopic techniques and open surgery were the most common treatment modalities. The most common sites of residual gallstones were gallbladder remnant, cystic duct remnant and common bile duct. CONCLUSION: Residual gallbladder stones following incomplete gallbladder removal is an important sequelae after cholecystectomy. Completion cholecystectomy (open or laparoscopic) is the most common treatment modality reported in the literature for the management of residual gallbladder stones. PMID:26622110
[A rare case of gallbladder cancer with giardiasis].
Nagasaki, Toshiya; Komatsu, Hideaki; Shibata, Yoshihito; Yamaguchi, Hiroyuki; Nakashima, Masahiro
A 72-year-old man was referred to our hospital for suspected gallbladder cancer. We performed cholecystectomy with liver bed resection and lymph node dissection. Intraoperative cytological examination of the bile juice revealed some trophozoites of Giardia lamblia, and pathological examination revealed gallbladder cancer. Therefore, we diagnosed giardiasis associated with gallbladder cancer. We administered 750 mg per day metronidazole for 10 days. The patient was a farmer by occupation and used animal manure for agricultural purposes; he also consumed his own harvest, which was recognized as the infection route for his giardiasis. We reviewed the literature and found very few cases of giardiasis associated with gallbladder cancer.
Gallbladder cancer: results achieved and future challenges.
Di Carlo, Isidoro; Toro, Adriana
26th World Congress of International Association of Surgeons Gastroenterologists and Oncologists, Seoul, South Korea, 8-10 September 2016 This year, the 26th World Congress of the International Association of Surgeons, Gastroenterologists, and Oncologists (IASGO) was hosted by Seoul in South Korea. The congress was extremely well organized, and the quality of the submissions and the relevance of the speakers were excellent. This report highlights the newest and most interesting results regarding the treatment of gallbladder tumors from the conference.
[Ultrasound of gallbladder and bile duct].
Segura Grau, A; Joleini, S; Díaz Rodríguez, N; Segura Cabral, J M
The cystic nature of the gallbladder and bile duct when dilated, and the advantages of ultrasound as a quick, reproducible, convenient, cheap and low risk technique, with a high sensitivity and specificity, make it the most eligible technique in biliary pathology studies. Ultrasound has become a valuable tool for doctors studying biliary pathology and its complications, from abnormal liver function results, right upper quadrant pain, or jaundice, to cholelithiasis, cholecystitis, or suspicion of biliary tumors.
Synchronous extraskeletal Ewing's sarcoma/PNET and gallbladder carcinoma: a case report and literature review
Zygulska, Aneta; Püsküllüoğlu, Mirosława; Szczepański, Wojciech; Białas, Magdalena; Krupiński, Maciej; Krzemieniecki, Krzysztof
Ewing's sarcoma (ES) and primitive neuroectodermal tumour (PNET) are now considered to be the same tumour and usually occur in long bones. Extraskeletal Ewing's sarcoma is an extremely rare neoplasm, accounting for 1% of soft tissue sarcomas, with most common location in the thorax. Gallbladder cancer (GBC) represents the most common type among the biliary tract cancers with a poor prognosis even among patients undergoing aggressive therapy. We present study of extraskeletal ES/PNET found in the hilus of the liver of an elderly, diagnosed one month prior with GBC woman. The patient underwent two cycles of chemotherapy SAIME/SAVAC for ES and thereafter was operated. During three-year follow-up no recurrence of ES/PNET has been reported. However, two years after chemotherapy the patient suffered a relapse of adenocarcinoma of the gallbladder and thus received palliative chemotherapy of gemcitabine and cisplatin. After 16 months of recurrence she died. To the best of our knowledge, this is the first case of ES/PNET located in the hilus of the liver and as a synchronous neoplasm. PMID:28239290
Myeloproliferative neoplasm stem cells.
Mead, Adam J; Mullally, Ann
Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.
Genomics of Myeloproliferative Neoplasms.
Zoi, Katerina; Cross, Nicholas C P
Myeloproliferative neoplasms (MPNs) are a group of related clonal hematologic disorders characterized by excess accumulation of one or more myeloid cell lineages and a tendency to transform to acute myeloid leukemia. Deregulated JAK2 signaling has emerged as the central phenotypic driver of BCR -ABL1-negative MPNs and a unifying therapeutic target. In addition, MPNs show unexpected layers of genetic complexity, with multiple abnormalities associated with disease progression, interactions between inherited factors and phenotype driver mutations, and effects related to the order in which mutations are acquired. Although morphology and clinical laboratory analysis continue to play an important role in defining these conditions, genomic analysis is providing a platform for better disease definition, more accurate diagnosis, direction of therapy, and refined prognostication. There is an emerging consensus with regard to many prognostic factors, but there is a clear need to synthesize genomic findings into robust, clinically actionable and widely accepted scoring systems as well as the need to standardize the laboratory methodologies that are used.
Myeloproliferative Neoplasms in Children
Hofmann, Inga
Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders characterized by aberrant proliferation of one or more myeloid lineages often with increased immature cells in the peripheral blood. The three classical BCR-ABL-negative MPNs are: 1) polycythemia vera (PV), 2) essential thrombocythemia (ET), and 3) primary myelofibrosis (PMF), which are typically disorders of older adults and are exceedingly rare in children. The diagnostic criteria for MPNs remain largely defined by clinical, laboratory and histopathology assessments in adults, but they have been applied to the pediatric population. The discovery of the JAK2 V617F mutation, and more recently, MPL and CALR mutations, are major landmarks in the understanding of MPNs. Nevertheless, they rarely occur in children, posing a significant diagnostic challenge given the lack of an objective, clonal marker. Therefore, in pediatric patients, the diagnosis must rely heavily on clinical and laboratory factors, and exclusion of secondary disorders to make an accurate diagnosis of MPN. This review focuses on the clinical presentation, diagnostic work up, differential diagnosis, treatment and prognosis of the classical BCR-ABL-negative MPNs (PV, ET and PMF) in children and highlights key differences to the adult diseases. Particular attention will be given to pediatric PMF, as it is the only disorder of this group that is observed in infants and young children, and in many ways appears to be a unique entity compared to adult PMF. PMID:26609329
Myeloproliferative Neoplasms (MPNs) Patient Registry
Primary Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Mastocytosis; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Juvenile; Chronic Eosinophilic Leukemia-not Otherwise Specified; Myelodysplastic-Myeloproliferative Diseases; Neoplasms; Leukemia, Myelomonocytic, Chronic
Are histological alterations observed in the gallbladder precancerous lesions?
Meirelles-Costa, Adriana Lúcia Agnelli; Bresciani, Claudio José Caldas; Perez, Rodrigo Oliva; Bresciani, Barbara Helou; Siqueira, Sheila Aparecida C.; Cecconello, Ivan
INTRODUCTION Gallbladder cancer, which is characterized by rapid progression and a poor prognosis, is a complex disease to treat. Unfortunately, little is known currently about its etiology or pathogenesis. A better understanding of its carcinogenesis and determining risk factors that lead to its development could help improve the available treatment options. METHOD Based on this better understanding, the histological alterations (such as acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis, polyps, pyloric metaplasia, intestinal metaplasia, dysplasia, cancer and others) in gallbladders from 1,689 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis were analyzed. The association of these gallbladder histological alterations with clinical data was studied. RESULTS Gender analysis revealed a greater incidence of inflammatory changes in males, while dysplasia and cancer were only found in women. The incidence of cholesterolosis was greater in the patients 60 years of age and under, and the incidence of adenomyomatosis and gangrene was greater in the elderly patients. A progressive increase in the average age was observed as alterations progressed through pyloric metaplasia, intestinal metaplasia, dysplasia and then cancer, suggesting that the metaplasia-dysplasia-carcinoma sequence may occur in gallbladder cancer. Gallbladder histological alterations were also observed in asymptomatic patients. CONCLUSION The results of this study suggest that there could be an association between some histological alterations of gallbladder and cancer, and they also suggest that the metaplasia-dysplasia-carcinoma sequence could in fact be true in the case of gallbladder cancer. Nevertheless, further studies directed towards a perfect understanding of gallbladder carcinogenesis are required. PMID:20186297
Papillomatosis of the gallbladder associated with metachromatic leukodystrophy.
Burgess, J H; Kalfayan, B; Slungaard, R K; Gilbert, E
A 9-year-old boy with metachromatic leukodystrophy (MLD) was found to have diffuse papillomatosis of the gallbladder that was virtually obliterating the lumen of the gallbladder. To our knowledge, two other examples of this lesion have been reported previously in MLD.
Identification of a candidate stem cell in human gallbladder
Manohar, Rohan; Li, Yaming; Fohrer, Helene; Guzik, Lynda; Stolz, Donna Beer; Chandran, Uma R.; LaFramboise, William A.; Lagasse, Eric
There are currently no reports of the identification of stem cells in the human gallbladder. The differences between human gallbladder and intrahepatic bile duct (IHBD) cells have also not been explored. The goals of this study were to evaluate if human fetal gallbladder contains a candidate stem cell population and if fetal gallbladder cells are distinct from fetal IHBD cells. We found that EpCAM+CD44+CD13+ cells represent the cell population most enriched for clonal self-renewal from primary gallbladder. Primary EpCAM+CD44+CD13+ cells gave rise to EpCAM+CD44+CD13+ and EpCAM+CD44+CD13− cells in vitro, and gallbladder cells expanded in vitro exhibited short-term engraftment in vivo. Last, we found that CD13, CD227, CD66, CD26 and CD49b were differentially expressed between gallbladder and IHBD cells cultured in vitro indicating clear phenotypic differences between the two cell populations. Microarray analyses of expanded cultures confirmed that both cell types have unique transcriptional profiles with predicted functional differences in lipid, carbohydrate, nucleic acid and drug metabolism. In conclusion, we have isolated a distinct clonogenic population of epithelial cells from primary human fetal gallbladder with stem cell characteristics and found it to be unique compared to IHBD cells. PMID:25765520
Adenomyomatosis of the gallbladder resembling honeycomb in a child.
Akçam, Mustafa; Buyukyavuz, Ilker; Ciriş, Metin; Eriş, Naim
Adenomyomatosis of the gallbladder is believed to be an uncommon pathologic condition of the gallbladder in childhood. Only three pediatric cases have been described in the literature up to now. Honeycomb gallbladder has been described in two adult patients; no patients have been reported in childhood until now. To the best of our knowledge, we report here the first case of adenomyomatosis of the gallbladder which resembled honeycomb, in a 9-year-old girl presented with recurrent abdominal pain. The diagnosis was made by ultrasound, and confirmed by magnetic resonance cholangiopancreatography and finally cholecystectomy. In conclusion, ultrasound scanning performed more generally in children presenting with recurrent abdominal pain might lead to accurate diagnosis of adenomyomotosis of the gallbladder during childhood.
Necrotizing fasciitis secondary to carcinoma of the gallbladder with perforation.
Okada, Ken-ichi; Shatari, Tomoo; Yamamoto, Tatsuma; Sasaki, Takahiro; Suwa, Tatsushi; Furuuchi, Takayuki; Takenaka, Yoshifumi; Hori, Masao; Sakuma, Masayoshi
We present an unusual case of necrotizing fasciitis in the upper abdominal wall caused by penetrating perforation of the gallbladder. It was manifested as an elastic and reddish abdominal swelling with severe tenderness, but no peritoneal irritation. Computed tomography (CT) demonstrated water density with a slightly elevated CT value and air bubbles in the subcutaneous space. The preoperative diagnosis was subcutaneous abscess with fasciitis. At surgery, necrotizing fasciitis and subcutaneous abscess secondary to penetrating perforation of the gallbladder were revealed. Cholecystectomy and peritoneal irrigation were performed. Although no tumor was evident during surgery, a tumor located close to the perforation site was found just after the operation. Pathological examination revealed gallbladder carcinoma without stones. There have been very few previous reports of necrotizing fasciitis following gallbladder perforation. The presentation, diagnosis, and management of fasciitis, as well as carcinoma of the gallbladder with perforation, are discussed.
Coexistence of xanthogranulomatous cholecystitis and gallbladder adenocarcinoma: a fortuitous association?
Limaiem, F; Chelly, B; Hassan, F; Haddad, I; Ben Slama, S; Lahmar, A; Bouraoui, S; Mzabi-Regaya, S
Xanthogranulomatous cholecystitis is a relatively uncommon variant of chronic cholecystitis, characterized by marked thickening of the gallbladder wall and dense local adhesions. Not only does xanthogranulomatous cholecystitis mimic malignancy, it can also be infrequently associated with gallbladder carcinoma in 0.2% to 35.4% of cases. Herein, the authors report a new case of xanthogranulomatous cholecystitis concomitant with gallbladder adenocarcinoma in a 65-year-old female patient. Because of its overlapping clinical, radiological and macroscopic findings with gallbladder cancer, definitive diagnosis of xanthogranulomatous cholecystitis relies on extensive sampling and thorough microscopic examination of the surgical specimen to exclude the possibility of coexisting tumour. It is still a matter of debate whether xanthogranulomatous cholecystitis is truly a precursor of gallbladder carcinoma or if it is just an incidental finding. This aspect needs to be explored in the future with further studies.
Time to reconsider Spitzoid neoplasms?
Urso, Carmelo
SUMMARY Background: Spitzoid neoplasms may pose significant diagnostic problems because in a fraction of them it is quite difficult or impossible to establish if they are benign or malignant lesions. An extraordinarily large number of studies have been made in attempts to solve this problem; regrettably, the histological criteria proposed and the various special sophisticated techniques employed have proven to be ineffective in making this distinction with confidence. Objectives: To explore the possible causes for this diagnostic failure and an attempt to identify the source of this problem. Method: A historical and technical analysis of the specialized literature is performed, critically evaluating the main points of this controversial topic. Results: The reasons for the diagnostic failure in Spitzoid neoplasms are not clear but could be the result of inappropriate conceptual representation. The analysis of available data and a rational review of old and new assumptions and concepts may suggest a different representation for Spitzoid neoplasms: Spitz nevus, atypical Spitz tumor and Spitzoid melanoma, rather than being three different tumors that are difficult or impossible to distinguish with assurance, could be viewed as one unique entity, Spitz tumor (ST). This tumor is a low-grade malignant neoplasm, in which the amount of intrinsic risk is variable, ranging from very low to high (ST1, ST2, ST3), and malignant potential could be estimated. Conclusions: The proposed alternative representation of Spitzoid neoplasms as a unique tumor may help in overcoming the difficulty in diagnosis of these tumors. PMID:27222771
Dumbbell Gallbladder Cholecystitis on Tc-99m Diisopropyliminodiacetic acid Hepatobiliary Imaging
Fakhri, Asif Ali; Rodrigue, Paul David; Hussain, Aun; Taiyebi, Abbas
We present a case of a 79-year-old immunocompromised female admitted for abdominal pain and sepsis, who had an abdominal computed tomography (CT) showing distal gallbladder fundus wall thickening, pericholecystic edema, and a right posteroinferior hepatic abscess. Subsequent hepatobiliary scintigraphy with Tc-99m diisopropyliminodiacetic acid showed gallbladder filling of the proximal gallbladder fundus, yet no radiotracer filling of the distal gallbladder fundus. Further correlation with the initial CT showed a partial gallbladder stricture and a resultant altered morphology resembling a dumbbell-shaped gallbladder. Percutaneous cholangiogram also confirmed this dumbbell morphology. Nonfilling of radiotracer into the distal end of the dumbbell gallbladder correlating with CT findings of focal gallbladder inflammation indicated that there was a focal inflammation suggesting a distal dumbbell gallbladder cholecystitis. This case demonstrates a unique finding of focal inflammatory pathology involving an anatomic variant - the dumbbell-shaped gallbladder, and the challenges this anatomic variant presents in hepatobiliary scintigraphy image interpretation. PMID:28242983
Staging of neoplasms. Volume 7
Glazer, G.M.
This book is divided into ten chapters. The first, an overview of the importance of staging, is followed by separate chapters on computed tomographic (CT) evaluation of lymph node metastases; metastatic disease to the thorax; staging of laryngeal, hypopharyngeal, esophageal, non-small cell lung, and renal carcinoma; and pediatric abdominal malignancies. CT staging of lymphomas is dealt with in a separate chapter. The final chapter summarizes initial experiences with staging of neoplasms by magnetic resonance (MR) imaging. Other neoplasms, such as pelvic, pancreatic, and gastrointestinal, are not discussed in depth. The book concludes with ten case studies, most of which deal with pelvic and gastrointestinal malignancies.
Gallbladder perforation by absorbable spiral tacker
Wirsching, A; Vonlanthen, R
Introduction Mesh fixation with tacker systems is common in laparoscopic and open hernia repair. Complications due to absorbable tackers are rare and have not been described in the literature. However, we report a case of gallbladder erosion due to tacker dislocation. Methods An open hernia repair was performed using an intraperitoneal onlay mesh for a recurrent parastomal hernia after two previous mesh repairs in a 67-year-old patient. Results On postoperative day 2, the patient was reoperated because of a dislocated tacker that eroded and perforated the fundus region of the gallbladder. Putatively, tacker dislocation occurred owing to imbalanced traction forces. Initially, the mesh was fixed with absorbable tackers around the stoma on the right and transmuscular suture fixation was carried out on the left abdominal side. On revision surgery, tension forces to the right were therefore neutralised by additional transmuscular sutures on the right side. Conclusions Absorbable tackers in open hernia repair provide a safe and effective mesh fixation if tension forces are carefully avoided. PMID:25245719
Left-sided gallbladder associated with congenital liver cyst
Colovic, N.; Barisic, G.; Atkinson, H. D. E.; Krivokapic, Z.
Background. A left-sided gallbladder is a rare congenital anomaly defined as a gallbladder attached to the lower surface of the left lateral segment of the liver, i.e. to the left of the interlobar fissure and round ligament. Case outlines. In two women aged 42 and 70 years a left-sided gallbladder was associated with a congenital cyst of the liver. In the first patient, the ectopic gallbladder was an incidental finding at operation for a symptomatic liver cyst; as the gallbladder was normal it was not removed. The second patient underwent operation for chronic calculous cholecystitis, when the left-sided gallbladder and congenital liver cyst were found. An operative cholangiogram was normal, the cystic duct joining the common bile duct from the right side. The gallbladder was removed, and the cyst was de-roofed. Both patients had an uneventful recovery and remain symptom-free at 12 and 9 years respectively. Discussion. To the best of our knowledge, the association of these two congenital anomalies has not been described previously. PMID:18333268
Effects of melatonin on gallbladder neuromuscular function in acute cholecystitis.
Gomez-Pinilla, Pedro J; Camello, Pedro J; Pozo, María J
Gallbladder stasis is associated to experimental acute cholecystitis. Impaired contractility could be, at least in part, the result of inflammation-induced alterations in the neuromuscular function. This study was designed to determine the changes in gallbladder neurotransmission evoked by acute inflammation and to evaluate the protective and therapeutic effects of melatonin. Experimental acute cholecystitis was induced in guinea pigs by common bile duct ligation for 2 days, and then the neuromuscular function was evaluated using electrical field stimulation (EFS; 5-40 Hz). In a group of animals with the bile duct ligated for 2 days, a deligation of the duct was performed, and after 2 days, the neuromuscular function was studied. The EFS-evoked isometric gallbladder contraction was significantly lower in cholecystitic tissue. In addition, inflammation changed the pharmacological profile of these contractions that were insensitive to tetrodotoxin but sensitive to atropine and omega-conotoxin, indicating that acute cholecystitis affects action potential propagation in the intrinsic nerves. Nitric oxide (NO)-mediated neurotransmission was reduced by inflammation, which also increased the reactivity of sensitive fibers. Melatonin treatment prevented qualitative changes in gallbladder neurotransmission, but it did not improve EFS-induced contractility. The hormone recovered gallbladder neuromuscular function once the biliary obstruction was resolved, even when the treatment was started after the onset of gallbladder inflammation. These findings show for the first time the therapeutic potential of melatonin in the recovery of gallbladder neuromuscular function during acute cholecystitis.
Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy
Bang, Chang Seok; Lee, Yong Sub; Yoon, Jai Hoon; Kim, Youn Jeong; Kim, Jin Bong; Kim, Dong Joon
Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis) who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116). In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P = 0.01) and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P = 0.04) were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P = 0.004) was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis. PMID:25705222
Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy.
Bang, Chang Seok; Lee, Yong Sub; Yoon, Jai Hoon; Kim, Youn Jeong; Kim, Jin Bong; Kim, Dong Joon
Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis) who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116). In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90-0.99, P = 0.01) and total serum cholesterol (OR: 1.02, 95% CI: 1.01-1.04, P = 0.04) were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94-0.99, P = 0.004) was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.
[Assessment of risk of death due to malignant neoplasms induced by occupational exposure in a rubber footwear plant].
Szymczak, Wiesław; Sobala, Wojciech; Wilczyńska, Urszula; Szeszenia-Dabrowska, Neonila
The main goal of the study was to analyze thoroughly the results of a cohort study. Such an analysis renders it possible to eliminate certain neoplasms as those not related to the observed exposure. The cohort study was carried out in a group of workers, covering 11,342 persons (5472 men and 5870 women), employed for at least one year during the years 1945-1985 in a rubber footwear plant. The cohort study was continued until the end of December 1997. Of all the sites of malignant neoplasms observed in the cohort, significant, exposure-related excess mortality was found to be due to malignant neoplasms of larynx and lung in men, and malignant neoplasms of gallbladder and lung in women. For these neoplasms, the values of observed risk among those exposed were significantly higher than among non-exposed. Moreover, in a certain interval of employment duration, an increase in risk rates with increasing duration of employment under exposure was observed, which suggests the presence of dose-response relationship. For all these sites, a relevant trend was shown by the RR values calculated in relation to the group of persons non-exposed but employed in the same plant. The internal reference group used to calculate RR values allowed to eliminate the effect of confounding variables, which is not always possible when the general population is used as the reference group.
Gallbladder epithelium as a niche for chronic Salmonella carriage.
Gonzalez-Escobedo, Geoffrey; Gunn, John S
Although typhoid fever has been intensively studied, chronic typhoid carriage still represents a problem for the transmission and persistence of the disease in areas of endemicity. This chronic state is highly associated with the presence of gallstones in the gallbladder of infected carriers upon which Salmonella can form robust biofilms. However, we hypothesize that in addition to gallstones, the gallbladder epithelium aids in the establishment/maintenance of chronic carriage. In this work, we present evidence of the role of the gallbladder epithelium in chronic carriage by a mechanism involving invasion, intracellular persistence, and biofilm formation. Salmonella was able to adhere to and invade polarized gallbladder epithelial cells apically in the absence and presence of bile in a Salmonella pathogenicity island 1 (SPI-1)-dependent manner. Intracellular replication of Salmonella was also evident at 12 and 24 h postinvasion. A flowthrough system revealed that Salmonella is able to adhere to and form extensive bacterial foci on gallbladder epithelial cells as early as 12 h postinoculation. In vivo experiments using a chronic mouse model of typhoid carriage showed invasion and damage of the gallbladder epithelium and lamina propria up to 2 months after Salmonella infection, with an abundant presence of macrophages, a relative absence of neutrophils, and extrusion of infected epithelial cells. Additionally, microcolonies of Salmonella cells were evident on the surface of the mouse gallbladder epithelia up to 21 days postinfection. These data reveal a second potential mechanism, intracellular persistence and/or bacterial aggregation in/on the gallbladder epithelium with luminal cell extrusion, for Salmonella maintenance in the gallbladder.
Intramural hemorrhage simulating gastric neoplasm.
Sheward, S E; Davis, M; Amparo, E G; Gogel, H K
We report a case of benign gastric ulcer with secondary extensive intramural hemorrhage causing a radiographic appearance consistent with a large ulcerated gastric neoplasm. This is the second such case reported and the first studied with sonography and computed tomographic scan. A brief review of the literature on intramural gastric hematoma is presented.
Drugs Approved for Myeloproliferative Neoplasms
This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.
Lipid Histiocytosis of the Gallbladder Neck Lymph Node
Ben Romdhane, Mohamed Habib; Straub, Beate Katharina
Lipid histiocytosis of the gallbladder neck lymph node is rarely reported nowadays. Two obese patients presented with gallbladder lithiasis detected on CT scan. The treatment consisted in coelioscopic cholecystectomy. Microscopy revealed subacute/chronic lithiasic cholecystitis and foci of vacuolated cells in the gallbladder neck lymph node. These cells were positive for CD68, CD31, S100 protein, and adipophilin and negative for cytokeratin and Alcian blue. In conclusion, we report lymph node lipid histiocytosis diagnosed microscopically after cholecystectomy. While such lesions may remain unidentified on imaging procedures, the microscopic analysis may require special stains and immunohistochemistry for ruling out adenocarcinoma metastasis. PMID:27847666
Lipid Histiocytosis of the Gallbladder Neck Lymph Node.
Handra-Luca, Adriana; Ben Romdhane, Mohamed Habib; Straub, Beate Katharina
Lipid histiocytosis of the gallbladder neck lymph node is rarely reported nowadays. Two obese patients presented with gallbladder lithiasis detected on CT scan. The treatment consisted in coelioscopic cholecystectomy. Microscopy revealed subacute/chronic lithiasic cholecystitis and foci of vacuolated cells in the gallbladder neck lymph node. These cells were positive for CD68, CD31, S100 protein, and adipophilin and negative for cytokeratin and Alcian blue. In conclusion, we report lymph node lipid histiocytosis diagnosed microscopically after cholecystectomy. While such lesions may remain unidentified on imaging procedures, the microscopic analysis may require special stains and immunohistochemistry for ruling out adenocarcinoma metastasis.
Analysis of blood and tissue in gallbladder cancer
NASA Astrophysics Data System (ADS)
Rautray, T. R.; Vijayan, V.; Sudarshan, M.; Panigrahi, S.
Particle induced X-ray emission, particle induced γ-ray emission studies has been carried out to analyse normal and carcinoma tissues and blood samples of gallbladder of both sexes and seventeen trace elements namely Na, Mg, Al, K, Ca, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br and Pb were estimated in the tissue and blood samples. In the present study, concentration of Zn in the carcinoma gallbladder tissue is less than that of the normal gallbladder tissue. Tobacco habit could be one of the important factors to decrease the elemental concentrations in blood and tissue samples.
Impact of lymph node ratio as a valuable prognostic factor in gallbladder carcinoma, focusing on stage IIIB gallbladder carcinoma
Choi, Byung-Gwan; Kim, Choong-Young; Cho, Seung-Hyun; Kim, Hee-Joon; Koh, Yang-Seok; Kim, Jung-Chul; Cho, Chol-Kyoon; Kim, Hyun-Jong
Purpose It is increasingly being recognized that the lymph node ratio (LNR) is an important prognostic factor for gallbladder carcinoma patients. The present study evaluated predictors of tumor recurrence and survival in a large, mono-institutional cohort of patients who underwent surgical resection for gallbladder carcinoma, focusing specifically on the prognostic value of lymph node (LN) status and of LNR in stage IIIB patients. Methods Between 2004 and 2011, 123 patients who underwent R0 radical resection for gallbladder carcinoma at the Chonnam National University Hwasun Hospital were reviewed retrospectively. Patients were staged according to the American Joint Committee on Cancer 7th edition, and prognostic factors affecting disease free survival, such as age, sex, comorbidity, body mass index, presence of preoperative symptoms, perioperative blood transfusion, postoperative complications, LN dissection, tumor size, differentiation, lymph-vascular invasion, perineural invasion, T stage, presence of LN involvement, N stage, numbers of positive LNs, LNR and implementation of adjuvant chemotherapy, were statistically analyzed. Results LN status was an important prognostic factor in patients undergoing curative resection for gallbladder carcinoma. The total number of LNs examined was implicated with prognosis, especially in N0 patients. LNR was a powerful predictor of disease free survival even after controlling for competing risk factors, in curative resected gallbladder cancer patients, and especially in stage IIIB patients. Conclusion LNR is confirmed as an independent prognostic factor in curative resected gallbladder cancer patients, especially in stage IIIB gallbladder carcinoma. PMID:23487246
Hepatic neoplasms associated with contraceptive and anabolic steroids.
Ishak, K G
This paper evaluates the differences between HCA (hepatocellular adenoma) and FNH (focal nodular hyperplasia) and the association of HCA and FNH with OC (oral contraceptives). FNH occurs at least twice as frequent in females as in males. A study conducted by the author revealed that only 20% of patients with FNH had symptoms and signs related to their neoplasms; in the rest, FNH was accidentally discovered during surgery for diseases of the gallbladder or at necropsy. The highly characteristic gross appearance of FNH is discribed in detail. The etiologic relationship between FNH and OC was cited in the light of frequent findings of FNH in infants and children, and of suggestions by other authors that FNH could be a direct result on OC therapy or that contraceptive steroids or conjugated estrogens accelerate the growth of FNH, a very slow growing neoplasm. Simple excision is the treatment of choice for FNH; in some cases, hepatic artery ligation is indicated. In the case of HCA, statistics show that the incidence of HCA has been increasing since 1960. Majority of patients with HCA have normal tests of hepatic function. Radiographic studies and hepatic scans may reveal HCA, but the best diagnostic method so far is angiography. Although gross appearance of HCA is variable, the features are clearly distinguishable from that of FNH. Other topics discussed include the occasional occurence of nodular regenerative hyperplasia in patients on OC or anabolic steroids (AS), and malignant liver tumors in patients using OC or AS. Further research should be done to clarify the etiologic relationship between androgenic-anabolic steroids and hepatocellular tumors and tumorlike lesions.
Enhancing Targeted Therapy for Myeloproliferative Neoplasms
Myeloproliferative Neoplasms PRINCIPAL INVESTIGATOR: Gary W. Reuther CONTRACTING...2. REPORT TYPE Annual 3. DATES COVERED 30 2012-2 2013 4. TITLE AND SUBTITLE Enhancing Targeted Therapy for Myeloproliferative Neoplasms ...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Myeloproliferative neoplasms
How to image the gallbladder in suspected cholecystitis
Marton, K.I.; Doubilet, P.
As a result of important advances in medical imaging, the oral cholecystogram is no longer the primary test of gallbladder function and anatomy. Real-time ultrasonography and cholescintigraphy, both highly sensitive and specific tests, are the two major methods for assessing gallbladder pathology. Oral cholecystography, endoscopic retrograde pancreatography, and percutaneous gallbladder puncture serve as supplementary tests. Decisions about which test to use depend on the kind of gallbladder disease that is suspected as well as the estimated likelihood of the disease before the information is obtained from the procedure. Thus, ultrasonography is the test of choice for chronic cholecystitis, with oral cholecystography reserved for situations in which the diagnosis is uncertain after ultrasonography. When acute cholecystitis is suspected, ultrasonography is also the test of choice in most patients, and cholescintigraphy is used to resolve uncertainty. 103 references.
What Are the Risk Factors for Gallbladder Cancer?
... because both conditions can be related to inflammation). Female gender In the United States, gallbladder cancer occurs ... Car Ways to Give Memorial Giving Planned Giving Leadership Giving About ACS Contact Us Local Offices Employment ...
Gallbladder infarction following hepatic transcatheter arterial embolization: angiographic study
Kuroda, C.; Iwasaki, M.; Tanaka, T.; Tokunaga, K.; Hori, S.; Yoshioka, H.; Nakamura, H.; Sakurai, M.; Okamura, J.
Gallbladder infarction developing after transcatheter arterial embolization (TAE) in patients with malignant hepatic tumors was studied by comparing preoperative angiographic and postoperative macroscopic and histological findings. Eight patients demonstrated occlusion of the cystic artery or its branches by embolic materials on post-TAE angiograms. Surgery revealed infarction of the gallbladder in 6 patients; no infarction was noted in the other 2, although branches of the cystic artery were occluded on the post-TAE angiogram. Due to recanalization of the occluded artery, the infarcted area could be assessed only by follow-up angiography. No patient experienced perforation of the gallbladder as a result of infarction. The authors suggest that patients with post-TAE infarction of the gallbladder can be treated consevatively if they are kept under close observation.
Gallbladder Cancer in the 21st Century
Kanthan, Rani; Senger, Jenna-Lynn; Ahmed, Shahid; Kanthan, Selliah Chandra
Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC. PMID:26421012
Current Status on Cholangiocarcinoma and Gallbladder Cancer
Ebata, Tomoki; Ercolani, Giorgio; Alvaro, Domenico; Ribero, Dario; Di Tommaso, Luca; Valle, Juan W.
Background Cholangiocarcinomas (CC) as well as gallbladder cancers are relatively rare and intractable diseases. Clinical, pathological, and epidemiological studies on these tumors have been under investigation. The current status and/or topics on biliary tract cancers have been reported in the East West Association of Liver Tumor (EWALT), held in Milano, Italy in 2015. Summary All the authors, herein, specifcally reported the current status and leading-edge findings on biliary tract cancers as the following sequence: epidemiology of CC, surgical therapy for intrahepatic CC, surgical therapy for perihilar CC, surgical therapy for gallblad der cancer, chemotherapy for biliary tract cancers, and new histological features in CC. Key Message The present review article will update the knowledge on biliary tract cancers, en hancing the quality of daily clinical practice. However, many features about these cancers remain unknown; further studies are required to establish disease-specific optimal treatment strategies. PMID:27995089
Targeting the hedgehog pathway for gallbladder cancer therapy?
Mittal, Balraj; Yadav, Saurabh
Gallbladder carcinoma is a fatal malignancy of hepatobiliary tract that is generally diagnosed at advanced stages of cancer because of its asymptomatic nature. Advanced GBC tumors are unresectable with poor prognosis. Improvement in GBC patient care requires better understanding of the biological signaling pathways and application of newly discovered drugs for cancer therapy. Herein, we discuss the possibilities and challenges in targeting the hedgehog pathway in gallbladder cancer therapy based on recent developments in the area.
Gallbladder Carcinoma, the Difficulty of Early Detection: A Case Report
Lewis, Stephen L; Bear, Jonathan R; Van Echo, David C; Dainer, Hugh M
Gallbladder carcinoma (GBC) is an uncommon malignancy with a high mortality rate. Detecting gallbladder carcinoma in its early stages can be difficult, despite improvements in ultrasound and computed tomography (CT) imaging. Most diagnoses of GBC are made at advanced stages, with the majority being found incidentally during surgery for cholelithiasis. The presented case demonstrates the difficulty of diagnosing GBC preoperatively in its early stages. PMID:27014527
[Scintigraphic study of gallbladder emptying in chronic Chagas' disease].
Troncon, L E; Rezende Filho, J; Iazigi, N
Previous studies on gallbladder motility in Chagas' disease, which is known to be associated with diffuse destruction of intramural neurons, have produced conflicting results. In the present study we reevaluated this question by submitting chronic chagasic patients (n = 18) and controls (n = 12) to a cholescintigraphic study of gallbladder emptying in response to a single intra-venous injection of 60 ng/kg cerulein 90 min after administration of 99mTC-HIDA. Five min. before and immediately before carulein injection, as well as every 5 min. up to 45 min. after the stimulus, images of the gallbladder were obtained with a gamma-camera coupled to a computer. The counts obtained for regions of interest corresponding to the gallbladder, permitted the calculation of the ejection fraction of the organ and the construction of individual gallbladder emptying curves. The ejection fractions values for the total sample of chagasic patients (median 67.8%; variation, 4.0 to 99.0%), although higher than those for the control group (median: 34.2% variation, 13.1 to 88.0%), were not statistically significant (p greater than 0.05). However, analysis of the individual curves for the chagasics permitted identifying 2 subgroups, one of which (n = 9) showed values very similar to those for the controls, whereas the other (n = 9) showed a very rapid and intense gallbladder emptying. It is concluded that impairment of the gallbladder innervation in Chagas' disease may lead to heterogeneous patterns of gallbladder emptying, with some patients being definitely hypersensitive to an exogenous cholecystokinetic agent.
[Lithotripsy of gallbladder calculi with extracorporeal shockwaves].
Nogueira, C E; Martins, F P; Dani, R
Two hundred and sixty two patients with gallbladder stones were prospectively evaluated at the Biliary Lithiasis Treatment Unit of the Mater Dei Hospital, Belo Horizonte, MG., and 45 (17.5%) were selected for extracorporal shock wave lithotripsy (ECSWL). From these, 32 were submitted to the procedure. One stone was present in 30 patients, 2 stones in another and 1 patient had 3 stones. The mean diameter was 14.7 mm ranging from 8 to 28 mm. ECSWL was preceded by 1 week course of ursodeoxycholic acid (8 to 10 mg/dk/day) and this medication was continued after the procedure. ECSWL was done with the Lithosthar-Plus apparatus (Siemens). Meperidine (up to 100 mg) IM and pirazolene IV was given when necessary. The intensity of the shock waves was gradually increased to a maximum (9 bar) whenever tolerated. The treatment was well succeeded in 22 cases (71%) with pulverization in 12 (38.7%). In 9 patients (29%) remaining fragments were greater than 4 mm. From these, 3 were submitted to a second session of ECSWL. In 1 patient the stone could not be properly positioned for lithotripsy. The mean number of shock waves was 2,591, ranging from 801 to 4,411. The mean duration of the sessions was 80 min, ranging from 45 to 150 min. In 3 patients, a complete disappearance of fragments was observed in intervals of 1 to 6 months after the procedure. One patient had severe pain during ECSWL and developed acute cholecystitis. One patient had sinus bradycardia. One patient with total stone pulverization, become jaundiced 1 month after ECSWL and a gallbladder carcinoma was found at surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Spontaneous endomyometrial neoplasms in aging Chinese hamsters
Brownstein, D.G.; Brooks, A.L.
Twenty-one endomyometrial neoplasms among 93 nulliparous noninbred Chinese hamsters were evaluated. The median survival time of the 93 females was 1040 days. The median age of hamsters with endomyometrial neoplasms was 1200 days. Neoplasms were classified as carcinomas or malignant mixed muellerian tumors of the endometrium and benign or malignant myometrial neoplasms. There were 13 endometrial adenocarcinomas. Three tumors were mixed adenosquamous carcinomas, which occurred in significantly older Chinese hamsters than did adenocarcinomas. Three malignant mixed muellerian tumors consisted of 2 carcinosarcomas and 1 mixed mesodermal tumor. The 2 myometrial neoplasms were a lelomyoma and a lelomyosarcoma. The classification and relative frequency of these neoplasms were similar to endomyometrial neoplasms of women, which makes Chinese hamsters useful subjects for studies of spontaneous endomyometrial cancers.
Giant gallbladder: A case report and review of literature
Kuznetsov, A.V.; Borodach, A.V.; Fedin, E.N.; Khromova, A.D.
INTRODUCTION Reports of a giant gallbladder are rare. PRESENTATION OF CASE A 77-year-old woman was admitted with complaints of dull pain in the right half of the abdomen and a palpable mass at the same place. A computerized tomography scan revealed an extremely enlarged gallbladder. Open cholecystectomy was performed. The volume of the removed organ was as much as 3.35 L. Follow-up after 18 months showed that the patient was well. Examination revealed no significant acquired or congenital anomalies that might explain the excessive enlargement of the gallbladder. DISCUSSION We define a 'giant' gallbladder as an extreme enlargement of the organ with a volume exceeding 1.5 L, so that its weight is comparable to or even exceeds the mean (estimated) weight of the adult liver (1.5 kg). The first clinical presentation of such an enlargement is likely to differ from any other gallbladder disease, but rather to resemble a tumour or cyst of the abdominal cavity. CONCLUSION A giant gallbladder is a special clinical and pathological entity in surgical practice, of unknown origin. It may develop in patients of any age, and mimics a large abdominal tumour or peritoneal cyst. Both the diagnostic process and surgical treatment demand non-routine approaches. Early and late follow-up results seem to be favourable. PMID:25194602
3D shape decomposition and comparison for gallbladder modeling
NASA Astrophysics Data System (ADS)
Huang, Weimin; Zhou, Jiayin; Liu, Jiang; Zhang, Jing; Yang, Tao; Su, Yi; Law, Gim Han; Chui, Chee Kong; Chang, Stephen
This paper presents an approach to gallbladder shape comparison by using 3D shape modeling and decomposition. The gallbladder models can be used for shape anomaly analysis and model comparison and selection in image guided robotic surgical training, especially for laparoscopic cholecystectomy simulation. The 3D shape of a gallbladder is first represented as a surface model, reconstructed from the contours segmented in CT data by a scheme of propagation based voxel learning and classification. To better extract the shape feature, the surface mesh is further down-sampled by a decimation filter and smoothed by a Taubin algorithm, followed by applying an advancing front algorithm to further enhance the regularity of the mesh. Multi-scale curvatures are then computed on the regularized mesh for the robust saliency landmark localization on the surface. The shape decomposition is proposed based on the saliency landmarks and the concavity, measured by the distance from the surface point to the convex hull. With a given tolerance the 3D shape can be decomposed and represented as 3D ellipsoids, which reveal the shape topology and anomaly of a gallbladder. The features based on the decomposed shape model are proposed for gallbladder shape comparison, which can be used for new model selection. We have collected 19 sets of abdominal CT scan data with gallbladders, some shown in normal shape and some in abnormal shapes. The experiments have shown that the decomposed shapes reveal important topology features.
Interstitial Cajal-like cells in human gallbladder.
Hinescu, Mihail E; Ardeleanu, Carmen; Gherghiceanu, Mihaela; Popescu, Laurentziu M
We describe here an interstitial Cajal-like cell type (ICLC) in human gallbladder, resembling the archetypal enteric interstitial cells of Cajal. Gallbladder ICLC were demonstrated in fresh preparations (tissue cryosections) using methylene-blue, and fixed specimens in Epon semi-thin sections stained with toluidine blue or transmission electron microscopy (TEM). The positive diagnosis of gallbladder ICLC was further verified by immunohistochemistry: CD117/c-kit, CD34, and another 16 antigens: vimentin, desmin, nestin, alpha-smooth muscle actin, NK-1, S-100, PGP-9.5, tau protein, chromogranin A, NSE, GFAP, CD1a, CD62-P, CD68, estrogen and progesterone receptors. Double immunostaining was performed for CD117, CD34 and CD117 and nestin, respectively. In fresh specimens, the spatial density of gallbladder ICLC was 100-110 cells/mm(2). ICLC mainly appeared beneath the epithelium and in muscularis (about 7%, and approximately 5%, respectively). In toto, ICLC represent in gallbladder approximately 5.5% of subepithelial cells. TEM showed that diagnostic criteria were fulfilled by ICLC. Moreover, TEM indicated that the main ultrastructural distinctive feature for ICLC, the cell processes, develop into the characteristic shape at a relatively early stage of development. It remains to be established if, in humans, ICLC are involved in gallbladder (dis)functions (e.g. pace-making, secretion (auto-, juxta- and/or paracrine), intercellular signaling, or stone formation).
Clinicopathologic characteristics of young patients with gallbladder cancer.
Do, Sung-Im; Lee, Hyoun Wook; Sohn, Jin Hee; Kim, Kyungeun
Gallbladder cancer is the most common biliary tract cancer and the fifth most common cancer of the digestive system. However, the clinicopathologic features of gallbladder cancer in young Korean patients have not been studied. This study included 101 consecutive cases of gallbladder cancer that underwent cholecystectomy at Kangbuk Samsung Hospital from December 1990 to March 2011. The patients were divided into two groups by age at initial diagnosis of gallbladder cancer: a young patient group aged less than 45 years and an old patient group aged 45 or older. The young patient group included 10 patients with mean age of 38 (range, 29-44 years). Compared with the old patient group, the young patient group showed polypoid tumor appearance (p=0.014), lower pT stage (p=0.023), more frequent adenoma background (p=0.009), and less frequent dysplasia in remaining mucosa (p=0.001). The disease-related survival rate after 13.5 months was significantly more favorable for the young patients. Gallbladder cancers in young Korean patients have distinct clinicopathologic features of a high frequency of cancer arising in adenoma, rare association with intestinal metaplasia and dysplasia, and a favorable patient's prognosis. These findings suggest that the adenoma-carcinoma pathway could contribute more to gallbladder cancer carcinogenesis in young Korean patients than the metaplasia-dysplasia-carcinoma pathway.
Cardiac effects of noncardiac neoplasms
Schoen, F.J.; Berger, B.M.; Guerina, N.G.
Clinically significant cardiovascular abnormalities may occur as secondary manifestations of noncardiac neoplasms. The principal cardiac effects of noncardiac tumors include the direct results of metastases to the heart or lungs, the indirect effects of circulating tumor products (causing nonbacterial thrombotic endocarditis, myeloma-associated amyloidosis, pheochromocytoma-associated cardiac hypertrophy and myofibrillar degeneration, and carcinoid heart disease), and the undesired cardiotoxicities of chemotherapy and radiotherapy. 89 references.
Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones.
Kratzer, W; Mason, R A; Haag, U; Maier, C; Janowitz, P; Beckh, K; Adler, G
In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities < 100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5 +/- 11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones < 20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P = 0.0567) and in group II from 6.5 ml to 20.2 ml (P = 0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)
Classification of Salivary Gland Neoplasms.
Bradley, Patrick J
Presently, there is no universal 'working' classification system acceptable to all clinicians involved in the diagnosis and management of patients with salivary gland neoplasms. The most recent World Health Organization Classification of Tumours: Head and Neck Tumours (Salivary Glands) (2005) for benign and malignant neoplasms represents the consensus of current knowledge and is considered the standard pathological classification based on which series should be reported. The TNM classification of salivary gland malignancies has stood the test of time, and using the stage groupings remains the current standard for reporting treated patients' outcomes. Many developments in molecular and genetic methods in the meantime have identified a number of new entities, and new findings for several of the well-established salivary malignancies need to be considered for inclusion in any new classification system. All clinicians involved in the diagnosis, assessment and treatment of patients with salivary gland neoplasms must understand and respect the need for the various classification systems, enabling them to work within a multidisciplinary clinical team environment.
Microscopic examination of gallbladder stones improves rate of detection of Clonorchis sinensis infection.
Qiao, Tie; Ma, Rui-hong; Luo, Xiao-bing; Zheng, Pei-ming; Luo, Zhen-liang; Yang, Liu-qing
To improve the rate of detection of Clonorchis sinensis infection, we compared different specimens from patients with cholecystolithiasis. Feces, gallbladder bile, and gallbladder stones collected from 179 consecutive patients with cholecystolithiasis underwent microscopic examination, and according to the results, 30 egg-positive and 30 egg-negative fecal, gallbladder bile, and gallbladder stone specimens, respectively, underwent real-time fluorescent PCR. The detection rates of eggs in feces, bile, and gallbladder stones were 30.7%, 44.7%, and 69.8%, respectively, and the differences were statistically significant (P<0.01). The PCR results confirmed that the eggs in the specimens were C. sinensis eggs. Eggs in the feces were "fresh" and in the gallbladder stones were "old." Microscopic examination of gallbladder stones may improve the detection rates of C. sinensis infection, which is important for developing individualized treatments to prevent the recurrence of gallbladder stones and to prevent the occurrence of severe liver damage and cholangiocarcinoma.
Weekes, R.G.; McLeod, R.A.; Reiman, H.M.; Pritchard, D.J.
The computed tomographic scans (CT) of 84 patients with untreated soft-tissue neoplasms were studied, 75 with primary and nine with secondary lesions. Each scan was evaluated using several criteria: homogeneity and density, presence and type of calcification, presence of bony destruction, involvement of multiple muscle groups, definition of adjacent fat, border definition, and vessel or nerve involvement. CT demonstrated the lesion in all 84 patients and showed excellent anatomic detail in 64 of the 75 patients with primary neoplasms. The CT findings were characteristic enough to suggest the histology of the neoplasm in only 13 lesions (nine lipomas, three hemangiomas, one neurofibroma). No malignant neoplasm had CT characteristics specific enough to differentiate it from any other malignant tumor. However, malignant neoplasms could be differentiated from benign neoplasms in 88% of the cases.
Tc-99m HIDA cholescintigraphy: the distended photon-deficient gallbladder
Zeman, R.K.; Segal, H.B.; Caride, V.J.
Four patients with distended, photon-deficient gallbladders are presented. Markedly delayed appearance of Tc-99m HIDA in a distended gallbladder may represent chronic cholecystitis, partial obstruction of the common bile duct, or physiologic gallbladder distention. Obtaining delayed images is important in this group of patients to avoid premature diagnosis of cystic-duct obstruction. If the distended gallbladder fails to visualize within 24 hr, hydrops with cysic-duct obstruction is suggested.
Tc-99m HIDA cholescintigraphy: the distended photon-deficient gallbladder
Zeman, R.K.; Segal, H.B.; Caride, V.J.
Four patients with distended, photon-deficient gallbladders are presented. Markedly delayed appearance of Tc-99m HIDA in a distended gallbladder may represent chronic cholescystitis, partial obstruction of the common bile duct or physiologic gallbladder distention. Obtaining delayed images is important in this group of patients to avoid premature diagnosis of cystic-duct obstruction. If the distended gallbladder fails to visualize within 24 h, hydrops with cystic-duct obstruction is suggested.
Isolated rupture of the gallbladder following blunt abdominal trauma: case report
Epstein, Marina Gabrielle; da Silva, Dorivaldo Lopes; Elias, Naim Carlos; Sica, Gustavo Tricta Augusto; Fávaro, Murillo de Lima; Ribeiro, Marcelo Augusto Fontenelle
ABSTRACT Gallbladder rupture following blunt abdominal trauma is a rare event recognized on evaluation and treatment of other visceral injuries during laparotomy. Isolated gallbladder rupture secondary to blunt abdominal trauma is even more uncommon. The clinical presentation of gallbladder injury is variable, resulting in a delay in diagnosis and treatment. We report the case of a patient who suffered an isolated gallbladder rupture due to blunt abdominal trauma. PMID:23843066
Second Malignant Neoplasms Following Radiotherapy
Kumar, Sanath
More than half of all cancer patients receive radiotherapy as a part of their treatment. With the increasing number of long-term cancer survivors, there is a growing concern about the risk of radiation induced second malignant neoplasm [SMN]. This risk appears to be highest for survivors of childhood cancers. The exact mechanism and dose-response relationship for radiation induced malignancy is not well understood, however, there have been growing efforts to develop strategies for the prevention and mitigation of radiation induced cancers. This review article focuses on the incidence, etiology, and risk factors for SMN in various organs after radiotherapy. PMID:23249860
[Gallbladder motor activity in patients with virus hepatitis B].
Mamos, Arkadiusz; Wichan, Paweł; Chojnacki, Jan; Grzegorczyk, Krzysztof
In acute stage of virus hepatitis B patients often complain of dyspeptic discomfort. They may be a consequence of alimentary tract motor activity disorders including these of gallbladder. Routine ultrasonography in an early phase of virus hepatitis often reveals gallbladder wall thickening what may confirm the above thesis. Thus, a group of 15 patients in an acute phase of virus hepatitis B was subjected to examinations. Gallbladder motor activity was assessed by ultrasonographic method determining its total volume and ejection fraction and volume after test meal stimulus. First examination was performed in the first week since the appearance of yellowing of the walls, successive in 4 and 8 week of the disease. Obtained results were compared to the values obtained in the group of 25 healthy volunteers. It was found out that gallbladder volume was significantly decreased and ejection fraction increased in the acute phase of virus hepatitis B than in the controls. This may speak for gallbladder hyperreactivity in patients in the course of virus hepatitis B. These disorders decreased during two-month observation but even in the 8 week the investigated parameters differed from those found in the control group.
Gallbladder opacification on gadoxetate disodium-enhanced CT scan.
Karam, Adib R; Scortegagna, Eduardo; Chen, Byron Y; Dupuis, Carolyn S; Coughlin, Dennis D
This study aimed to evaluate the radiologist's ability to identify excreted gadoxetate disodium within the gallbladder on CT scan. Thirty three healthy adults underwent imaging of the liver during work-up for potential liver donation. Three patients had undergone prior cholecystectomy and therefore were excluded. Imaging consisted of gadoxetate disodium-enhanced magnetic resonance cholangiography (MRC) and multiphase contrast-enhanced CT scan of the abdomen and pelvis. Two fellowship-trained abdominal imaging radiologists, who were blinded to the MRC images and the contrast agent used during MRC, independently reviewed the CT scans of the 30 patients that were included. The scans were evaluated for the presence or absence of abnormal hyperdensity within the gallbladder. Three patients did not receive intravenous gadoxetate disodium, 4 patients had their MRC after the CT scan, and 1 patient had the CT scans 5 days following the MRC. Twenty two patients had the CT scan within 24 h following the gadoxetate disodium-enhanced MRC. Of the 22 patients expected to have gadolinium in the gallbladder, both reviewers identified hyperdensity in the same 20 patients (90%). Both reviewers reported no abnormal hyperdensity within the gallbladder in the remaining 10 patients. CT scan can reveal excreted gadoxetate disodium within the gallbladder lumen and therefore gadoxetate disodium-enhanced CT scan can potentially play a role in the evaluation of cystic duct patency and work-up of acute cholecystitis.
Percutaneous gallbladder aspiration for acute cholecystitis
Rassameehiran, Supannee; Nugent, Kenneth
Early cholecystectomy for patients with acute cholecystitis may not be possible in some clinical settings. Percutaneous gallbladder aspiration (PGBA) offers an alternative approach, but the benefits and risks of this procedure are unclear. We synthesized data on the outcomes of PGBA in acute cholecystitis patients using data sources from online databases, including MEDLINE and EMBASE, and bibliographies of included studies from January 2000 through December 2015. Two reviewers independently reviewed and critiqued the quality of each study. Seven eligible studies met our criteria. The success rates in single PGBA and repetitive PGBA (2–4 times) were 50% to 93% and 76% to 96%, respectively. Complication rates were 0% to 8% and were unrelated to the size of needle gauge used for aspiration and the number of aspirations. Salvage percutaneous cholecystostomy (PC) and urgent surgery were required in 0% to 43% of patients and 0% to 4% of patients, respectively. Two studies with antibiotic instillation had clinical success rates of 95% and 96%. In conclusion, repetitive PGBA combined with antibiotic instillation and salvage PC are useful alternatives to early cholecystectomy in patients with acute cholecystitis. PMID:27695167
Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer
Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
Preoperative predictive factors for gallbladder cholesterol polyp diagnosed after laparoscopic cholecystectomy for polypoid lesions of gallbladder
Lee, Hyojin; Park, Inseok; Cho, Hyunjin; Gwak, Geumhee; Yang, Keunho; Bae, Byung-Noe; Kim, Hong-Ju; Kim, Young Duk
Backgrounds/Aims We investigated patients' clinical and radiological data to determine preoperative factors that predict cholesterol gallbladder (GB) polyps of large size, which can be helpful for decision on further diagnostic tools. Methods In this study, we retrospectively analyzed 126 patients who underwent laparoscopic cholecystectomy for GB polyps >10 mm diagnosed preoperatively by abdominal ultrasonography between February 2002 and February 2016 in Department of Surgery, Sanggye Paik Hospital. Patients were divided into non-cholesterol polyps group and cholesterol polyps group, based on the postoperative pathologic diagnosis. Clinical and radiological data, such as gender, age, body weight, height, body mass index (BMI), laboratory findings, size, number and shape of the polypoid lesions, and presence of the concurrent GB stone were compared between the two groups. Results Of the 126 cases, 73 had cholesterol polyps (57.9%) and 53 cases were non-cholesterol polyps (42.1%). The younger age (<48.5 years), size of polyp <13.25 mm and multiple polyps were independent predictive variables for cholesterol polyps, with odd ratios (OR) of 2.352 (p=0.045), 5.429 (p<0.001) and 0.472 (p<0.001), respectively. Conclusions Age, size and polyp number were used to predict cholesterol GB polyp among polypoid lesions of the gallbladder >10 mm. For cases in which these factors are not applicable, it is strongly recommended to evaluate further diagnostic tools, such as computed tomography, endoscopic ultrasonography and tumor markers. PMID:28261697
The Spindle Cell Neoplasms of the Oral Cavity
Shamim, Thorakkal
Spindle cell neoplasms are defined as neoplasms that consist of spindle-shaped cells in the histopathology. Spindle cell neoplasms can affect the oral cavity. In the oral cavity, the origin of the spindle cell neoplasms may be traced to epithelial, mesenchymal and odontogenic components. This article aims to review the spindle cell neoplasms of the oral cavity with emphasis on histopathology. PMID:26351482
Uterine adenosarcomas are mesenchymal neoplasms
Piscuoglio, Salvatore; Burke, Kathleen A; Ng, Charlotte KY; Papanastasiou, Anastasios D; Geyer, Felipe C; Macedo, Gabriel S; Martelotto, Luciano G; de Bruijn, Ino; De Filippo, Maria R; Schultheis, Anne M; Ioris, Rafael A; Levine, Douglas A; Soslow, Robert A; Rubin, Brian P; Reis-Filho, Jorge S; Weigelt, Britta
Uterine adenosarcomas (UA) are biphasic lesions composed of a malignant mesenchymal (i.e. stromal) component and an epithelial component. UAs are generally low-grade and have a favourable prognosis, but may display sarcomatous overgrowth (SO), which is associated with a worse outcome. We hypothesized that, akin to breast fibroepithelial lesions, UAs are mesenchymal neoplasms where clonal somatic genetic alterations are restricted to the mesenchymal component. To characterize the somatic genetic alterations in UAs and to test this hypothesis, we subjected 20 UAs to a combination of whole-exome (n=6), targeted capture (n=13) massively parallel sequencing (MPS) and/or RNA-sequencing (n=6). Only three genes, FGFR2, KMT2C and DICER1, were recurrently mutated, all in 2/19 cases; however, 26% (5/19) and 21% (4/19) of UAs harboured MDM2/CDK4/HMGA2 and TERT gene amplification, respectively, and two cases harboured fusion genes involving NCOA family members. Using a combination of laser capture microdissection and in situ techniques, we demonstrated that the somatic genetic alterations detected by MPS were restricted to the mesenchymal component. Furthermore, mitochondrial DNA sequencing of microdissected samples revealed that epithelial and mesenchymal components of UAs were clonally unrelated. In conclusion, here we provide evidence that UAs are genetically heterogeneous lesions and mesenchymal neoplasms. PMID:26592504
[Etiopathogenic hypothesis on carcinoma of the gallbladder: our study].
Rizzo, A G; Barbuscia, M; Sanò, M; Cancellieri, A; Nicotina, P; Stassi, G; Lemma, G; Lemma, F
The authors are interested in determining causes of gallbladder cancer (GBC). By this intention, they theorize a correlation between genetic modifications (which are responsible of malignant transformation of biliary epithelium) and some intestinal infections. From 1999 to 2004 they observed 15 GBC and all 15 gallbladder have been analyzed histologically and from microbiological aspect; by these means from 1999 till 2004 they have studied also 30 persons with colelithiasis. The authors noticed that bile of both groups contained, in three cases in the first and in 8 cases in the second, a germ named Escherichia Coli which normally lives in intestine, while in 10 operated gallbladders of the first group and 12 of the second there was a positive for k-ras. They are studying to confirm their theories.
Pathology of the gallbladder in a child with metachromatic leukodystrophy.
McFadden, Kathryn; Ranganathan, Sarangarajan
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A, leading to an accumulation of sulfatide in myelinating cells and progressive central and peripheral demyelination. Sulfatide also accumulates in various organs, most notably the gallbladder. Gallbladder mucosal hyperplasia with papillomatosis, in the setting of abdominal pain and hemobilia, is often demonstrated by sonography. We present a histologic and ultrastructural description of these alterations in a 5-year-old girl with MLD who presented with abdominal pain and feeding intolerance. Gross and light microscopic analysis demonstrated diffuse villous hyperplasia of the gallbladder mucosa with intraepithelial and intravillous macrophage accumulations of metachromatic material. Electron microscopic analysis demonstrated this material to comprise numerous membrane-bound inclusions composed of concentrically lamellated, dense material. The rarity of descriptions of this finding prompted this case report.
Gallbladder intestinal metaplasia in Pakistani patients with gallstones.
Khan, Muhammad Rizwan; Raza, Syed Ahsan; Ahmad, Zubair; Naeem, Sana; Pervez, Shahid; Siddiqui, Anwar Ali; Ahmed, Mushtaq; Azami, Rizwan
The gallbladder specimens of patients who underwent cholecystectomy for symptomatic gallstones between 2003 and 2005 were evaluated for the presence of Intestinal Metaplasia. (IM) and its risk factors. IM was positive in 39% of 293 patients tested, and in the comparative analysis of 114 metaplasia positive versus 179 negative patients, a high risk was found in patients who were 60 years or older [adjusted odds ratio (aOR) = 3.0, 95% confidence interval (CI): 1.5, 6.2]. Other factors with aOR greater than 1 were moderate to excessive use of chilies (1.8) and ethnic origin of North India (1.7). Screening method has yet to be devised for early detection of gallbladder cancer by identifying metaplastic lesions early in life. We believe that large geographic variation and lifestyle environmental factors associated with the development of gallbladder metaplasia and cancer mortality are concealed in our study that needs to be further explored.
Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery
Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage II Gallbladder Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer
Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle.
Macias, Beatriz; Gomez-Pinilla, Pedro J; Camello-Almaraz, Cristina; Pascua, Patricia; Tresguerres, Jesus Af; Camello, Pedro J; Pozo, Maria J
Calcium sensitization is an important physiological process in agonist-induced contraction of smooth muscle. In brief, calcium sensitization is a pathway that leads to smooth muscle contraction independently of changes in [Ca(2+)](i) by mean of inhibition of myosin light chain phosphatase. Aging has negative impacts on gallbladder contractile response due to partial impairment in calcium signaling and alterations in the contractile machinery. However, information regarding aging-induced alterations in calcium sensitization is scanty. We hypothesized that the calcium sensitization system is negatively affected by age. To investigate this, gallbladders were collected from adult (4 months old) and aged (22-24 months old) guinea pigs. To evaluate the contribution of calcium sensitization pathways we assayed the effect of the specific inhibitors Y-27632 and GF109203X on the "in vitro" isometric gallbladder contractions induced by agonist challenges. In addition, expression and phosphorylation (as activation index) of proteins participating in the calcium sensitization pathways were quantified by Western blotting. Aging reduced bethanechol- and cholecystokinin-evoked contractions, an effect associated with a reduction in MLC20 phosphorylation and in the effects of both Y-27632 and GF109203X. In addition, there was a drop in ROCK I, ROCK II, MYPT-1 and PKC expression and in the activation/phosphorylation of MYPT-1, PKC and CPI-17 in response to agonists. Interestingly, melatonin treatment for 4 weeks restored gallbladder contractile responses due to re-establishment of calcium sensitization pathways. These results demonstrate that age-related gallbladder hypocontractility is associated to alterations of calcium sensitization pathways and that melatonin treatment exerts beneficial effects in the recovery of gallbladder contractility.
Angioarchitecture of the rabbit extrahepatic bile ducts and gallbladder.
Jackowiak, Hanna; Lametschwandtner, Alois
The angioarchitecture of extrahepatic bile ducts and gallbladder of the miniature rabbit was studied by scanning electron microscopy (SEM) of vascular corrosion casts. Light microscopy of Masson-stained, paraffin-embedded transverse tissue sections served to attribute cast vascular structures to defined layers of bile ducts and gallbladder. In all segments of the bile tract, a mucosal and a subserosal vascular network was found. In glandular segments, the mucosal network was composed of a meshwork of subepithelial and circumglandular capillaries, which serve the mucosal functions. Differences in the angioarchitectonic patterns existed only in the subserosal networks as hepatic ducts own one supplying arteriole only, while the common bile duct owns a well-defined rete arteriosum subserosum. A well-developed dense subserosus venous plexus was present throughout the bile tract. Vascular patterns of the gallbladder body resembled those of the bile duct, whereby the dense subserous venous plexus was located close to the mucosal capillary network. The subserosal network in the neck of the gallbladder resembled that of the cystic duct. Spatial changes of the mucosal vascular network during volume changes of the gallbladder were documented. Measurements from tissue sections revealed bile tract diameters of 220-400 microm (extrahepatic ducts), 500-650 microm (cystic duct), and 4-6 mm (common bile duct). Data gained from high-powered SEM micrographs of vascular corrosion casts revealed vessel diameters of 200 microm (cystic artery), 90-110 microm (cystic vein), 30-40 microm (feeding arterioles), and 25-110 microm (subserosal venules). Crypt diameters in the filled gallbladder were 300-1,500 mum; those in the contracted organ were 100-600 microm.
Code of Federal Regulations, 2010 CFR
... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Neoplasms. 311.11 Section 311.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.11 Neoplasms. (a)...
Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)
... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...
Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)
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Visceral Obesity If Associated with Gallbladder Polyps
Lee, Jun Kyu; Hahn, Suk Jae; Kang, Hyoun Woo; Jung, Jae Gu; Choi, Han Seok; Lee, Jin Ho; Han, In Woong; Jung, Jin-Hee; Kwon, Jae Hyun
Background/Aims Gallbladder polyps (GBP) are a common clinical finding and may possess malignant potential. We conducted this study to determine whether visceral obesity is a risk factor for GBP. Methods We retrospectively reviewed records of subjects who received both ultrasonography and computed tomography with measurements of the areas of visceral adipose tissue and total adipose tissue (TAT) on the same day as health checkups. Results Ninety-three of 1,615 subjects (5.8%) had GBP and were compared with 186 age- and sex-matched controls. VAT (odds ratio [OR], 2.941; 95% confidence interval [CI], 1.325 to 6.529; p=0.008 for the highest quartile vs the lowest quartile) and TAT (OR, 3.568; 95% CI, 1.625 to 7.833; p=0.002 for the highest quartile vs the lowest quartile) were independent risk factors together with hypertension (OR, 2.512; 95% CI, 1.381 to 4.569; p=0.003), diabetes mellitus (OR, 2.942; 95% CI, 1.061 to 8.158; p=0.038), hepatitis B virus positivity (OR, 3.548; 95% CI, 1.295 to 9.716; p=0.014), and a higher level of total cholesterol (OR, 2.232; 95% CI, 1.043 to 4.778; p=0.039 for <200 mg/dL vs ≥240 mg/dL). Body mass index and waist circumference were not meaningful variables. Conclusions Visceral obesity measured by VAT and TAT was associated with GBP irrespective of body mass index or waist circumference. PMID:26260756
[Benign neoplasms of female urethra].
Usunova, I; Vladimirov, V
In clinical practice neoplasms of female urethra are found usually in adult women. They can also be found in adolescent girls and as rare congenital abnormality. Those conditions are most frequently detected during gynecological or urological examination. Symptoms are few. Lesions are situated at the outer orifice of urethra at the broad basis. Authors have diagnosed and treated 331 patients between 26 and 87 years. Electro coagulation has been performed in 185 patients. Surgical excision has been performed in 41 patients. Excision with following electrocoagulation has been performed in 18 patients. Conservative treatment has been performed in 87 patients. Histological sample analysis has provided diagnosis of urethral polyp, caruncle and mucosal prolaps. Second electrocoagulation after surgical excision has been performed in 5 patients. Collaboration between urologists and gynecologists is essential for early diagnosis, prophylaxis and successful treatment of above mentioned diseases.
True left-sided gallbladder with a portal anomaly: report of a case.
Kawai, Ryosuke; Miyata, Kanji; Yuasa, Norihiro; Takeuchi, Eiji; Goto, Yasutomo; Miyake, Hideo; Nagai, Hidemasa; Hattori, Masaoki; Imura, Jiro; Hayashi, Yuuki; Kawakami, Jiro; Kobayashi, Yoichiro
A 65-year-old female who presented with back pain was diagnosed to have the presence of biliary sludge in the gallbladder. Computed tomography showed that the round ligament connected to the left portal umbilical portion was in the normal anatomical position. However, the gallbladder was located to the left of the middle hepatic vein and the round ligament, attached to the left lateral segment of the liver. The right posterior portal vein diverged alone from the main portal vein, and there was a long stem from the right anterior and left portal veins. Laparoscopic cholecystectomy confirmed the abnormal location of the gallbladder. Most reported cases of left-sided gallbladder are caused by a right-sided round ligament, which is called a "false" left-sided gallbladder. A case of left-sided gallbladder with a normal left-sided round ligament, which is designated as a case of "true" left-sided gallbladder, is extremely rare.
Respiratory response to mechanical stimulation of the gallbladder.
Stella, M H; Knuth, S L; Bartlett, D
Since stimuli from abdominal or pelvic viscera can affect respiratory muscle function, we hypothesized that mechanical stimulation of the gallbladder would result in inhibition of motor activity to the diaphragm and to upper airway muscles. We studied 12 decerebrate, vagotomized, paralyzed, artificially ventilated cats and recorded hypoglossal (HG) and phrenic (PHR) nerve activities while applying 600-1000 g of traction on the gallbladder during four respiratory cycles. Traction resulted in an initial reduction of PHR activity to 87.6+/-15.0% (mean+/-S.D.% of its baseline value), a reduction of HG activity to 74.2+/-27.5% and a lengthening of expiratory time to 178.8+/-81.0%. Subsequently, PHR activity and expiratory time returned toward control values, while HG remained diminished, at 66.4+/-19.1%. Our results show that mechanical stimulation of the gallbladder results in a respiratory inhibition with a disproportionate reduction in HG activity relative to PHR discharge. We speculate that gallbladder stimulation by contractions or surgery may compromise breathing by inhibition of phrenic discharge and upper airway obstruction.
[Paraneoplastic dermatomyositis as a clue to occult gallbladder carcinoma].
Maroñas Jiménez, Lidia; Larraín Páez, Hugo; Restrepo Garcia, Ángela; Zarco Olivo, Carlos; Vanaclocha Sebastián, Francisco
Adult-onset dermatomyositis (DM) is an idiopathic inflam- matory myopathy frequently associated with underlying cancer, including gastrointestinal tumors. However, its as- sociation with carcinomas of the hepatobiliary tract is exceptional. We present a case of paraneoplastic DM occurring as the first and only clinical manifestation of an underlying carcinoma of gallbladder.
Work in progress: nuclear magnetic resonance imaging of the gallbladder
Hricak, H.; Filly, R.A.; Margulis, A.R.; Moon, K.L.; Crooks, L.E.; Kaufman, L.
A preliminary study of the relation between food intake and intensity of gallbladder bile on nuclear magnetic resonance (NMR) images was made. Twelve subjects (seven volunteers, five patients) were imaged following a minimum of 14 hours of fasting. Six of seven volunteers were reimaged one hour after stimulation by either a fatty meal or an alcoholic beverage. An additional seven patients were imaged two hours after a hospital breakfast. It was found that concentrated bile emits a high-intensity spin echo signal (SE), while hepatic bile in the gallbladder produces a low-intensity SE signal. Following ingestion of cholecystogogue, dilute hepatic bile settles on top of the concentrated bile, each emitting SE signals of different intensity. The average T1 value of concentrated bile was 594 msec, while the T1 vaue of dilute hepatic bile was 2,646 msec. The average T2 values were 104 msec for concentrated bile and 126 msec for dilute bile. The most likely cause for the different SE intensities of bile is the higher water content, and therefore longer T1 or T2 relaxation times, of hepatic bile. It is suggested that NMR imaging has the ability to provide physiological information about the gallbladder and that it may prove to be a simple and safe clinical test of gallbladder function.
Association of Gallbladder Polyp and Stroke
Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung
Abstract Gallbladder polyp (GP) and stroke share several metabolic disorders as risk factors. We assessed the association between GP and subsequent stroke risk. From 2000 to 2011, patients with GP aged >20 years were identified from the Longitudinal Health Insurance Database 2000. Of the 15,975 examined patients, 12,780 and 3195 were categorized into the non-GP and GP cohorts, respectively. The relative risks of stroke were estimated using the Cox proportional hazard model after adjusting for age, sex, and comorbidities. The overall incidence of stroke was higher in the GP cohort than in the non-GP cohort (6.66 vs 5.20/1000 person-yr), with an incidence rate ratio (IRR) of 1.28 (95% confidence interval [CI] = 1.15–1.42). The risk of stroke was 1.32-fold (95% CI = 1.06–1.63) in patients with GP compared with patients without GP after adjusting for age, sex, income level, urbanization level, occupation and comorbidities of gallstone, alcohol-related illness, diabetes, hyperlipidemia, hypertension, obesity, COPD, coronary heart disease, and asthma. Furthermore, the stroke risk was higher among elderly patients (with 1-yr intervals; adjusted HR [aHR] = 1.06, 95% CI = 1.05–1.07), the male sex (aHR = 1.62, 95% CI = 1.35–1.96), lower income level (aHR = 1.37, 95% CI = 1.02–1.85 for level I; aHR = 1.62, 95% CI = 1.25–2.10 for level II), living in second urbanized areas (aHR = 1.28, 95% CI = 1.00–1.63), alcohol-related illness (aHR = 1.56, 95% CI = 1.07–2.28), diabetes (aHR = 1.78, 95% CI = 1.41–2.24), and hypertension (aHR = 2.74, 95% CI = 2.19–3.42). GP is associated with stroke; however, GP may be less influential than other risk factors are, such as male sex, lower income level, alcohol-related illness, diabetes, and hypertension, on stroke development. Additional studies are required to clarify whether GP is a risk factor for or an epiphenomenon of stroke development. PMID
Male reproductive system neoplasms. Special listing
Not Available
This Special Listing of Current Cancer Research Projects is a publication of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute. Each Listing contains descriptions of ongoing projects in one selected cancer research area. The research areas include: Experimental prostate carcinogenesis and related biology; Epidemiology of prostatic neoplasms; Preclinical studies of prostatic cancers; Diagnosis and prognosis of prostatic cancer; Therapy of prostatic cancer; Experimental testicular carcinogenesis and related biology; Epidemiology of testicular cancer; Diagnosis, prognosis and treatment of testicular neoplasms; Penile and other reproductive system neoplasms.
An ultrasonographic evaluation of gallbladder emptying in patients with cholelithiasis.
Agarwal, M; Agarwal, A K; Singh, S; Shukla, V K
Impaired gallbladder emptying producing biliary stasis may provide potent carcinogen, which comes in contact with gallbladder mucosa for a prolonged period, inducing carcinogenesis. The aim was to study gallbladder emptying pattern in cholelithiasis. Postprandial gallbladder emptying was measured ultrasonographically in terms of fasting volume (FV), postprandial residual volume at 30 minutes (PP30), 60 minutes (PP60), and 90 minutes (PP90), residual fraction, and ejection volume (EV) in 58 patients with gallstones. Patients were divided into two groups of poor and good contractors on the basis of 50% maximal postprandial gallbladder emptying. Malonaldehyde level was estimated in 15 patients with cholelithiasis. Twenty-nine patients (50%) were poor contractors. The FV in patients with cholelithiasis (mean, 30.08 mL) was larger than the controls (mean, 17.55 mL) and the difference was statistically significant (p < 0.02). The FV in the cholelithiasis group correlated significantly with the PP30 (r = 0.85, p < 0.001), PP60 (r = 0.85, p < 0.001), PP90 (r = 0.78, p < 0.001), and EV (r = 0.65, p < 0.001). Ejection volume was significantly less in poor contractors (p <0.001). Residual fraction was significantly higher in poor contractors (p < 0.001). The biliary malonaldehyde in poor contractors (2.27 micromol/mL) was higher than in good contractors (1.78 micromol/mL), but the difference was statistically not significant. Significantly larger volumes of PP30, PP60, PP90, and residual fraction and a low EV indicate poor contraction leading to biliary stasis.
Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study.
Pellegrini, C A; Ryan, T; Broderick, W; Way, L W
We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with 99mTc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder response to cholecystokinin (5 U/kg X h) was calculated from the gallbladder ejection fraction. Ten prairie dogs were then placed on a 0.4% cholesterol diet and 8 on a regular diet, and the studies were repeated 1, 2, and 6 wk later. The proportion of hepatic bile that entered the gallbladder relative to the intestine varied from one 15-min period to the next, and averaged 28.2% +/- 5.1% at 140 min. Partial spontaneous gallbladder emptying (ejection fraction 11.5% +/- 5.6%) was intermittently observed. Neither the number nor the ejection fraction of spontaneous gallbladder contractions changed during gallstone formation. By contrast, the percent of gallbladder emptying in response to cholecystokinin decreased from 72.1% +/- 5% to 25.9% +/- 9.3% (p less than 0.025) in the first week and was 14.3% +/- 5.5% at 6 wk (p less than 0.01 from prediet values, not significant from first week). Gallbladder filling decreased from 28.2% +/- 5.1% to 6.7% +/- 3% (p less than 0.01), but this change was only observed after 6 wk, when gallstones had formed. This study shows that bile flow into the gallbladder during fasting is not constant; the gallbladder contracts intermittently; gallbladder emptying in response to exogenous cholecystokinin is altered very early during gallstone formation; and gallbladder filling remains unaffected until later stages, when gallstones have formed.
Molecular diagnostics of myeloproliferative neoplasms.
Langabeer, Stephen E; Andrikovics, Hajnalka; Asp, Julia; Bellosillo, Beatriz; Carillo, Serge; Haslam, Karl; Kjaer, Lasse; Lippert, Eric; Mansier, Olivier; Oppliger Leibundgut, Elisabeth; Percy, Melanie J; Porret, Naomi; Palmqvist, Lars; Schwarz, Jiri; McMullin, Mary F; Schnittger, Susanne; Pallisgaard, Niels; Hermouet, Sylvie
Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN.
Computerized tomography in evaluation of hepatic neoplasms
Luna, R.F.; Resende, C.; Tishler, J.M.A.; Aldrete, J.S.; Shin, M.S.; Rubin, E.; Rahn, N.H.
The authors reviewed their experience with computerized tomography (CT) of the abdomen in 212 patients with histologically documented liver neoplasms seen during a 30-month period. The CT findings in cavernous hemangioma and focal nodular hyperplasia were specific, and permitted accurate diagnosis of this lesion before biopsy. The CT appearance of all other lesions was variable. CT is useful in providing an accurate evaluation of the intrahepatic and extrahepatic extent of the neoplasm.
miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer
Letelier, Pablo; García, Patricia; Leal, Pamela; Álvarez, Héctor; Ili, Carmen; López, Jaime; Castillo, Jonathan; Brebi, Priscilla; Roa, Juan Carlos
The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value < 0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P < 0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC. PMID:24966896
Clinical analysis of contributors to the delayed gallbladder opacification following the use of water-soluble contrast medium
Ku, Ming-Chang; Kok, Victor C; Lee, Ming-Yung; Hsu, Soa-Min; Lee, Pei-Yu; Chang, Che-Wei; Tyan, Yeu-Sheng; Juan, Chi-Wen
Objectives Gallbladder opacification (GBO) on computed tomography (CT) imaging may obscure certain pathological or emergent conditions in the gallbladder, such as neoplasms, stones, and hemorrhagic cholecystitis. This study aimed to investigate the clinical contributing factors that could predict the presence of delayed GBO determined by CT. Methods This study retrospectively evaluated 243 consecutive patients who received enhanced CT or intravenous pyelography imaging and then underwent abdominal CT imaging within 5 days. According to the interval between imaging, the patients were divided into group A (1 day), group B (2 or 3 days), and group C (4 or 5 days). Three radiologists evaluated CT images to determine GBO. Fisher's exact test and multivariate backward stepwise elimination logistic regression were performed. Results Positive GBO was significantly associated with the interval between imaging studies, contrast type, contrast volume, renal function, and hypertransaminasemia (P<0.05). Multivariate backward stepwise elimination logistic regression analysis of the three groups identified contrast type and hypertransaminasemia as independent predictors of GBO in group B patients (odds ratio [OR], 13.52, 95% confidence interval [CI], 1.72–106.38 and OR, 3.43, 95% CI, 1.31–8.98, respectively; P<0.05). Hypertransaminasemia was the only independent predictor of GBO in group C patients with an OR of 7.2 (95% CI, 1.62–31.73). Hypertransaminasemia was noted in three patients (100%) who initially underwent imaging 5 days prior to GBO. Conclusion Delayed GBO on CT imaging may be associated with laboratory hypertransaminasemia, particularly in patients receiving contrast medium over a period of ≥4 days. A detailed clinical history, physical examination, and further workup are of paramount importance for investigating the underlying cause behind the hypertransaminasemia. PMID:27660453
miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer.
Letelier, Pablo; García, Patricia; Leal, Pamela; Álvarez, Héctor; Ili, Carmen; López, Jaime; Castillo, Jonathan; Brebi, Priscilla; Roa, Juan Carlos
The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value<0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P<0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC.
[Detection of Clonorchis sinensis eggs in the ground gallbladder stones by microscopy].
Ma, Rui-Hong; Qiao, Tie; Luo, Xiao-Bing
Sera, feces, bile and gallbladder stones were collected from 179 patients who accepted gallbladder-preserving cholelithotomy during the period of January to June 2010 at the general surgery department in the Second People's Hospital of Panyu District in Guangzhou. Rapid colloidal gold immunochromatography was used to detect IgG against Clonorchis sinensis. C. sinensis eggs were examined by fecal direct smear, and in bile sediments and ground gallbladder stones. The results showed that the positive rate of rapid colloidal gold immunochromatographic assay for IgG was 51.4%, and the egg positive rate in feces, bile sediments and gallbladder stones was 30.7%, 44.7% and 69.8%, respectively. The detection rate of fecal direct smear was the lowest, while that of the gallbladder stone examination was the highest (P < 0.05). Those patients with egg-positive feces and/or bile sediments were all with egg-positive gallbladder stones.
Torsion of the gallbladder, localized in right subphrenic space in a patient with liver cirrhosis.
Maruyama, Yuichiro; Tanaka, Yuya; Yasunaga, Masafumi; Ogata, Kei; Tanaka, Hiroyuki; Akagi, Yoshito; Okuda, Koji
We report a case of torsion of the gallbladder displaced under the right subphrenic space in a patient with liver cirrhosis. An 82-year-old Japanese woman was admitted to our hospital for acute pain in the right upper quadrant. Clinical features suggested gallbladder torsion. She was under treatment for hepatitis C virus-related cirrhosis at our hospital. Abdominal CT showed the swollen fundus and body of the gallbladder under the right subphrenic space. Emergency laparoscopic cholecystectomy was performed. Intraoperative findings included a grossly necrotic gallbladder in the right subphrenic space with 360° clockwise torsion, together with liver cirrhosis and localized peritonitis. The clinical features and imaging findings in this rare case of misplaced gallbladder in right subphrenic space resembled those described in typical strangulated gallbladder. The displacement was probably related to right liver lobe atrophy associated with liver cirrhosis. Appropriate diagnosis and prompt surgical treatment are essential for a positive outcome.
Calreticulin Mutations in Myeloproliferative Neoplasms
Lavi, Noa
With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph−) myeloproliferative neoplasms (MPNs) in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET) and primary myelofibrosis (PMF). At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR) using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations) and recurrent 5-bp insertions (type 2 mutations) in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin) were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review. PMID:25386351
Breast metastasis from recurrent gallbladder adenocarcinoma: a case report with review of the literature
Faouzi, Houssin; Salmi, Nariman; Ettahri, Hamza; Elghissassi, Ibrahim; Mrabti, Hind; Errihani, Hassan
Gallbladder adenocarcinoma has a poor prognostic. The leading modes of dissemination in gallbladder cancer (GBC) are lymphatic, vascular, neural, intraperitoneal, and intraductal. The most common site of dissemination is liver. Breast metastasis in GBC is an unusual site of dissemination. Only few cases have been reported in the literature. We report a rare case of solitary breast metastasis from recurrent gallbladder carcinoma in light of existing literature. PMID:27512606
Autophagy-related vacuoles in mouse gallbladder epithelium.
Psenicnik, M; Veranic, P
The mouse gallbladder epithelial cells contain very heterogeneous vacuolar population. In an attempt to classify these vacuoles we identified NADPase and TPPase activity as well as the location of HRP which is used as the endocytotic marker. The results of the present study show that the vacuoles can be classified into three categories: (1) the vacuoles predominantly containing loose membrane coils related to the nascent autophagic vacuoles, (2) vacuoles containing densely packed membranes and exhibiting a positive HRP reaction, indicating the convergence of endocytotic and autophagic pathway, and (3) vacuoles composed of degraded membrane structures and containing the reaction product of NADPase activity, showing that the fusion of the lysosomes with the autophagosome-endosome took place. The highly developed cis, medial and trans Golgi compartments reflect the biosynthetic and endocytotic activity of the gallbladder epithelium.
On the growth rate of gallstones in the human gallbladder
NASA Astrophysics Data System (ADS)
Nudelman, I.
The growth rate of a single symmetrically oval shaped gallbladder stone weighing 10.8 g was recorded over a period of six years before surgery and removal. The length of the stone was measured by ultrasonography and the growth rate was found to be linear with time, with a value of 0.4 mm/year. A smaller stone growing in the wall of the gallbladder was detected only three years before removal and grew at a rate of ˜ 1.33 mm/year. The morphology and metallic ion chemical composition of the large stone and of a randomly selected small stone weighing about 1.1 g, extracted from another patient, were analyzed and compared. It was found that the large stone contained besides calcium also lead, whereas the small stone contained mainly calcium. It is possible that the lead causes a difference in mechanism between the growth of a single large and growth of multiple small gallstones.
Gallbladder visualization during technetium-99m RBC blood pool imaging. Case report and literature review
Kotlyarov, E.V.; Mattay, V.S.; Reba, R.C.
Gallbladder visualization occurred after a Tc-99m red blood cell (RBC) cardiac gated blood pool scan. To date, seven cases of gallbladder visualization after the intravenous injection of Tc-99m RBCs have been reported. In the previous six patients the gallbladder was visualized incidentally during a search for gastrointestinal (GI) bleeding. All of the patients were anemic, six of seven had chronic renal failure, and five of seven had received multiple blood transfusions. When interpreting GI bleeding scans in patients with anemia and renal failure, awareness of the possibility of gallbladder visualization in the delayed images is important to avoid false-positive results. 3 references.
Technetium-99m-HIDA visualization of an obstructed gallbladder via an accessory hepatic duct
Reimer, D.E.; Donald, J.W.
Technetium-99m-labeled iminodiacetic acid (HIDA) and paraisopropyliminodiacetic acid (PIPIDA) scintigraphy after sonographic evaluation of the gallbladder have been advocated recently for the diagnosis of acute obstructive cholecystitis and cholelithiasis. Several authors have stated or inferred that gallbladder visualization with /sup 99m/Tc-HIDA excludes acute cholecystitis and cystic duct obstruction. We describe a patient with surgically proven cystic duct obstruction whose gallbladder visualized on a /sup 99m/Tc-HIDA scan via an accessory hepatic duct which directly entered the gallbladder.
Honeycomb gallbladder: a very rare cause of right upper quadrant pain.
Aydin, Ramazan; Bilgici, Meltem Ceyhan; Polat, Ahmet Veysel; Aslan, Kerim; Kalayci, Ayhan Gazi
Honeycomb gallbladder is a rare congenital malformation of the gallbladder. In some cases, it may be asymptomatic, whereas in others, it may lead to symptoms consistent with biliary colic even in the absence of cholelithiasis. We present the clinical and imaging findings of a case of a 10-year-old boy who was admitted to the emergency department with right upper quadrant pain. Ultrasonography and magnetic resonance imaging showed a honeycomb gallbladder. Honeycomb gallbladder is safely diagnosed with ultrasonography, which should be part of the investigation of patients with right upper quadrant pain in the emergency department.
Gallbladder small cell carcinoma Xenograft established by serial transplantation in nude mice.
Nishime, Chiyoko; Ohnishi, Yasuyuki; Suemizu, Hiroshi; Tamaoki, Norikazu; Suematsu, Makoto; Oida, Yasuhisa; Yamazaki, Hitoshi; Nakamura, Masato; Ueyama, Yoshito; Kijima, Hiroshi
The GB-04-JCK xenograft line of human gallbladder small cell carcinoma was established in nude mice by serial transplantation. The xenotransplantability has been maintained for more than 20 years. The carcinoma cells grew in a solid-sheet pattern and were found to have hyperchromatic nuclei, finely dispersed chromatin and inconspicuous nucleoli in the primary gallbladder tumor, as well as in the established xenograft GB-04-JCK The carcinoma cells also had Grimelius argyrophil granules, electron-dense neuroendocrine granules bounded by a single membrane. The xenograft line retained histological and immunohistochemical characteristics of the primary gallbladder tumor and is the first reported xenotransplantable tumor of human gallbladder small cell carcinoma.
Light microscopy and scanning electron microscopy study on microstructure of gallbladder mucosa in pig.
Prozorowska, Ewelina; Jackowiak, Hanna
The present light microscopy (LM) and scanning electron microscopy (SEM) studies on porcine gallbladder mucosa provide a description of the microstructures of great functional importance such as mucosal folds, the epithelium, glands, and lymphatic nodules. The results showed the regional structural differences of the porcine gallbladder wall. Depending on the part of the gallbladder, three types of mucosal structures were described: simple and branched folds and mucosal crypts. An important structural feature found in the mucosa is connected with the structural variety of type of mucosal folds, which change from simple located in the neck, to most composed, i.e., branched or joined, in the polygonal crypts toward the fundus of the gallbladder. The morphometric analysis showed statistically significantly differences in the form and size of the folds and between the fundus, body, and neck of the gallbladder. Differences in the size of mucosal epithelium are discussed in terms of processes of synthesis and secretion of glycoproteins. Regional, species-specific differences in morphology of mucosal subepithelial glands, i.e., their secretory units and openings, and intensity of mucus secretion were described. Our results on the pig gallbladder show adaptation and/or specialization in particular areas of the mucosa for (1) secretion of mucus in the neck or body of gallbladder and (2) for cyclic volume changes, especially in the fundus of gallbladder. The description of the microstructures of mucosa in the porcine gallbladder could be useful as reference data for numerous experiments on the bile tract in the pig.
A comparative study of microstructural development in paired human hepatic and gallbladder biles.
Weihs, Daphne; Schmidt, Judith; Danino, Dganit; Goldiner, Ilana; Leikin-Gobbi, Diana; Eitan, Arieh; Rubin, Moshe; Talmon, Yeshayahu; Konikoff, Fred M
Cholesterol gallstones usually develop in the gallbladder and rarely form in bile ducts even in patients with highly lithogenic bile. Bile concentration and proteins (e.g. mucin) may affect crystallization, but the exact nature of this effect, especially in relation to crystallization pathways and microstructural evolution remains unclear. We examined lipid microstructures in paired hepatic and gallbladder biles to reveal ones that are essential for crystallization. Combining digital light microscopy with cryogenic-temperature transmission electron microscopy we are able to directly visualize and compare the time evolution of lipid microstructures in paired hepatic, gallbladder and diluted gallbladder biles of gallstone patients and controls, without drying or separating. Gallbladder bile exhibited several multilamellar vesicles and spheroidal micelles preceding and throughout crystallization. Vesicle morphology changed before crystallization was observed. In contrast, hepatic bile revealed almost no crystallization and while a variety of unilamellar vesicles and spheroidal micelles existed throughout the examination, multilamellar vesicles were rare. Diluted gallbladder bile was different from native gallbladder bile, as well as the paired hepatic bile, yielding occasional crystallization. Our findings suggest that maturing multilamellar vesicles precede (and at least partially initiate) crystallization in gallbladder bile. Although microstructural development seems to be concentration dependent, dilution of gallbladder bile to hepatic bile concentrations neither makes it identical to hepatic bile, nor prevents crystallization.
Effect of narcotic premedication of scintigraphic evaluation of gallbladder perforation
Sefczek, D.M.; Sharma, P.; Isaacs, G.H.; Brodmerkel, G.J. Jr.; Adatepe, M.H.; Powell, O.M.; Nichols, K.
A case of gallbladder perforation is presented in which a small bile leak was demonstrated by cholescintigraphy while the patient was receiving meperidine, but not after meperidine was discontinued. The scintigrams obtained during meperidine therapy also showed a pattern of bile-duct obstruction. It is suggested that increased biliary pressure secondary to meperidine admininstration permitted visualization of the leak. Use of narcotic drugs may be a useful pharmocologic intervention in cases of peritonitis due to small obscure bile leaks.
Tempol protects the gallbladder against ischemia/reperfusion.
Gomez-Pinilla, Pedro J; Camello, Pedro J; Tresguerres, Jesus A F; Pozo, María José
Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca(2+) influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-kappaB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca(2+) handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury.
Tumefactive Gallbladder Sludge at US: Prevalence and Clinical Importance.
Kim, Mimi; Kang, Tae Wook; Jang, Kyung Mi; Kim, Young Kon; Kim, Seong Hyun; Ha, Sang Yun; Sinn, Dong Hyun; Gu, Seonhye
Purpose To evaluate the prevalence of tumefactive sludge of the gallbladder detected at ultrasonography (US) and to assess whether any clinical and imaging differences exist between benign and malignant tumefactive sludge. Materials and Methods The institutional review board approved this retrospective study. The requirement for informed consent was waived. The study included a cohort (n = 6898) of patients with gallbladder sludge drawn from all adults (n = 115 178) who underwent abdominal US between March 2001 and March 2015. Tumefactive sludge was identified according to the following US findings: (a) nonmovable mass-like lesion and (b) absence of posterior acoustic shadowing at B-mode US and vascularity at color Doppler US. Follow-up examinations were arranged to ascertain whether the results showed true sludge or gallbladder cancer. Risk factors for malignant tumefactive sludge based on clinical and US characteristics were identified with multivariate logistic regression analysis. Results The prevalence of gallbladder and tumefactive sludge at abdominal US during the observation period was 6.0% (6898 of 115 178) and 0.1% (135 of 115 178), respectively. Twenty-eight (20.7%) patients were lost to follow-up. Of the 107 with tumefactive sludge, 15 (14%) were confirmed to have malignant tumefactive sludge. The risk factors for malignant tumefactive sludge were old age (odds ratio [OR], 1.06; P = .035), female sex (OR, 5.48; P = .014), and absence of hyperechoic spots within the sludge (OR, 6.78; P = .008). Conclusion Although the prevalence of tumefactive sludge at US was rare, a considerable proportion of patients had a malignancy. Careful follow-up is essential, especially for older patients, women, and those with an absence of hyperechoic spots at US. (©) RSNA, 2016 Online supplemental material is available for this article.
Clonorcis sinensis eggs are associated with calcium carbonate gallbladder stones.
Qiao, Tie; Ma, Rui-hong; Luo, Zhen-liang; Yang, Liu-qing; Luo, Xiao-bing; Zheng, Pei-ming
Calcium carbonate gallbladder stones were easily neglected because they were previously reported as a rare stone type in adults. The aim of this study was to investigate the relationship between calcium carbonate stones and Clonorchis sinensis infection. A total of 598 gallbladder stones were studied. The stone types were identified by FTIR spectroscopy. The C. sinensis eggs and DNA were detected by microscopic examination and real-time fluorescent PCR respectively. And then, some egg-positive stones were randomly selected for further SEM examination. Corresponding clinical characteristics of patients with different types of stones were also statistically analyzed. The detection rate of C. sinensis eggs in calcium carbonate stone, pigment stone, mixed stone and cholesterol stone types, as well as other stone types was 60%, 44%, 36%, 6% and 30%, respectively, which was highest in calcium carbonate stone yet lowest in cholesterol stone. A total of 182 stones were egg-positive, 67 (37%) of which were calcium carbonate stones. The C. sinensis eggs were found adherent to calcium carbonate crystals by both light microscopy and scanning electron microscopy. Patients with calcium carbonate stones were mainly male between the ages of 30 and 60, the CO2 combining power of patients with calcium carbonate stones were higher than those with cholesterol stones. Calcium carbonate gallbladder stones are not rare, the formation of which may be associated with C. sinensis infection.
Percutaneous Transcholecystic Biliary Interventions Using Gallbladder Anchors: Feasibility Study in the Swine
Lopera, Jorge E. Kirsch, David; Qian Zhong; Ruiz, Bernardo; Brazzini, Augusto; Gonzales, Arturo; Castaneda-Zuniga, Wilfrido
The purpose of this study was to report our initial experience with a swine model for biliary interventions by using a percutaneous transcholecystic access after suture anchor of the gallbladder. Telepaque tablets were given to five pigs to opacify the gallbladder. Under fluoroscopy, the opacified gallbladder was punctured percutaneously and three suture anchors were used to fix the anterior wall of the gallbladder to the abdominal wall. Two weeks later, the gallbladder was punctured and access into the distal common bile was obtained through the cystic duct. Balloon expandable stents were deployed into the distal common bile duct. Follow-up cholangiograms were obtained at 1 and 2 weeks. Necropsy was performed after 2 weeks to evaluate the relationship between the gallbladder and abdominal wall. Suture anchor placement was successful in all five pigs. One pig with a deep and highly positioned gallbladder developed fever, anorexia, and vomiting secondary to excessive stretch of the gallbladder. Placement of the guidewire through the extremely tortuous and small cystic ducts proved to be the most challenging step of the procedure. Metallic stents were successfully deployed in all four pigs in which it was attempted. Four animals tolerated the procedures without changes in their clinical conditions and no symptoms. Successful follow-up cholangiograms were performed at 1 and 2 weeks post-stent deployment without complications. All stents remained patent during the follow-up period. Necropsy demonstrated close attachment and adherence of the gallbladders to the antero-lateral abdominal wall in all four animals. Suture anchoring of the gallbladder is feasible in most pigs with superficially located gallbladders. This technique allows a safe and repeat access into the biliary system using a transcholecystic approach.
Angioarchitecture of gallbladder in pig: LM and SEM study on vascular microcorrosion casts.
Prozorowska, Ewelina; Jackowiak, Hanna
The study focused on the description of pig gallbladder angioarchitecture, with particular emphasis on the specifics of the course of blood vessels in individual layers of the gallbladder wall. Furthermore, the vascular systems of the pig gallbladder were analyzed in terms of the adaptation of this organ to changes in its volume during cyclical bile storage and discharge. The gallbladder is supplied by the cystic artery, which in the pig represents a mixed pinnate and bipinnate pattern of branching. The light microscopic and scanning electron microscopic observations of three-dimensional vascular corrosion casts showed the presence of two main complex vascular networks in the wall of the gallbladder, one located in the subserosal and the other in the mucosa. The unique features in the pig, connected with the size of the gallbladder, is the well-developed horizontal venous plexus under folds of the mucosa, which is a voluminous reservoir of fluids absorbed from bile and vascular networks around mucous glands. Superficial blood vessels of the gallbladder run in vascular pairs or triads, where a single artery runs between two veins. The structures of blood flow control, that is, venous valves, were observed only in venules of the subserosal plexus. Spatial arrangement of the vascular network in the pig gallbladder shows functional plasticity during changes in gallbladder volume. The course of superficial blood vessels in the well-filled gallbladder is arcuate, while in the empty gallbladder it is undulated or spiral. In the mucosal and intramural vessels the direction of blood vessels may change from perpendicular to oblique.
Comparison between cryoablation and irreversible electroporation of rabbit livers at a location close to the gallbladder
Qin, Zilin; Zhou, Liang; Fang, Gang; Chen, Jibing; Li, Jialiang; Niu, Lizhi; Liang, Bing; Xu, Kecheng
Abstract Background The ablation of liver tumors located close to the gallbladder is likely to lead to complications. The aim of this article is to compare the safety and efficacy of irreversible electroporation (IRE) and cryoablation in rabbit livers at a location close to the gallbladder. Materials and methods We performed cryoablation (n = 12) and IRE (n = 12) of the area of the liver close to the gallbladder in 24 New Zealand white rabbits in order to ensure gallbladder damage. Serum aminotransferase and serum bilirubin levels were measured before and after the ablation. Histopathological examination of the ablation zones in the liver and gallbladder was performed on the 7th day after the ablation. Result Seven days after the ablation, all 24 animals were alive. Gallbladder perforation did not occur in the IRE group; only mucosal epithelial necrosis and serous layer edema were found in this group. Gallbladder perforation occurred in four rabbits in the cryoablation group. Serum aminotransferase and serum bilirubin levels obviously increased in both groups by Day 3 and decreased gradually thereafter. The elevation in aminotransferase and bilirubin levels was greater in the cryoablation group than the IRE group. Pathological examination revealed complete necrosis of the liver parenchyma from the ablation center to the gallbladder in both groups, but bile duct and granulation tissue hyperplasia were observed in only the IRE group. Full-thickness gallbladder-wall necrosis was seen in the cryoablation group. Conclusions For ablation of the liver area near the gallbladder, IRE is superior to cryoablation, both in terms of safety (no gallbladder perforation in the IRE group) and efficacy (complete necrosis and rapid recovery in the IRE group). PMID:28265231
Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2.
Longo, W E; Panesar, N; Mazuski, J E; Kaminski, D
Acute cholecystitis is associated with increased gallbladder prostanoid formation and the inflammatory changes and prostanoid increases can be inhibited by nonsteroidal anti-inflammatory agents. Recent information indicates that prostanoids are produced by two cyclooxygenase (COX) enzymes, COX-1 and COX-2. The purpose of this study was to determine the COX enzymatic pathway in gallbladder mucosal cells involved in the production of prostanoids stimulated by inflammatory agents. Human gallbladder mucosal cells were isolated from cholecystectomy specimens and maintained in cell culture and studied in comparison with cells from a well differentiated gallbladder mucosal carcinoma cell line. COX enzymes were evaluated by Western immunoblotting and prostanoids were measured by ELISA. Unstimulated and stimulated cells were exposed to specific COX-1 and COX-2 inhibitors. In both normal and transformed cells constitutive COX-1 was evident and in gallbladder cancer cells lysophosphatidyl choline (LPC) induced the formation of constitutive COX-1 enzyme. While not detected in unstimulated normal mucosal cells and cancer cells, COX-2 protein was induced by both lipopolysaccharide (LPS) and LPC. Unstimulated gallbladder mucosal cells and cancer cells produced prostaglandin E2 (PGE2) and prostacyclin (6-keto prostaglandin F1alpha, 6-keto PGF1alpha) continuously. In freshly isolated normal gallbladder mucosal cells, continuously produced 6 keto PGF1alpha was inhibited by both COX-1 and COX-2 inhibitors while PGE2 levels were not affected. Both LPS and LPC stimulated PGE2 and 6 keto PGF1alpha formation were blocked by COX-2 inhibitors in freshly isolated, normal human gallbladder mucosal cells and in the gallbladder cancer cells. The prostanoid response of gallbladder cells stimulated by proinflammatory agents is inhibited by COX-2 inhibitors suggesting that these agents may be effective in treating the pain and inflammation of gallbladder disease.
Diagnosis and management of endocrine gland neoplasms
Weller, R.E.
Functional and nonfunctional neoplasms of the endocrine glands constitute some of the more challenging diagnostic and therapeutic problems in veterinary cancer medicine. The clinical signs are usually the result of an overproduction of hormones that are normally biosynthesized by the neoplastic endocrine gland (orthoendocrine syndromes), as opposed to those that are the result of hormones that are not normally biosynthesized and secreted by those cells that have undergone neoplastic transformation (paraendocrine syndromes, also known as endocrine paraneoplastic syndromes or ectopic hormone syndromes). The biological effects produced by a neoplasm may be out of proportion to the actual size of the tumor. This report focuses on the clinical signs and syndromes associated with neoplasms of the thyroid, adrenal glands and pancreas. Discussion will focus on the mechanisms producing the clinical signs, diagnosis, staging, therapy and prognosis. 2 tabs.
Intraductal Oncocytic Papillary Neoplasms of the Pancreas.
Kallen, Michael E; Naini, Bita V
Intraductal oncocytic papillary neoplasms (IOPNs) are cystic neoplasms with intraductal growth and complex papillae composed of oncocytic cells. IOPNs have been reported both in the pancreas and biliary tree, and are most likely closely related in these 2 locations. In the pancreas, these rare tumors are now considered 1 of the 4 histologic subtypes of intraductal papillary mucinous neoplasm (IPMN). Significant differences in histology, immunophenotype, and molecular genetics have been reported between IOPNs and other IPMN subtypes. However, there are limited data regarding the clinical behavior and prognosis of IOPNs in comparison to other subtypes of IPMN. We review features of pancreatic IOPNs and discuss the differential diagnosis of other intraductal lesions in the pancreas.
Conventional radiological strategy of common gastrointestinal neoplasms
Li, Yi-Zhuo; Wu, Pei-Hong
This article summarizes the clinical characteristics and imaging features of common gastrointestinal (GI) neoplasms in terms of conventional radiological imaging methods. Barium studies are readily available for displaying primary malignancies and are minimally or not at all invasive. A neoplasm may be manifested as various imaging findings, including mucosal disruption, soft mass, ulcer, submucosal invasion and lumen stenosis on barium studies. Benign tumors typically appear as smoothly marginated intramural masses. Malignant neoplasms most often appear as irregular infiltrative lesions on barium examination. Tumor extension to adjacent GI segments may be indistinct on barium images. Cross-sectional images such as computed tomography and magnetic resonance imaging may provide more accurate details of the adjacent organ invasion, omental or peritoneal spread. PMID:25628800
Recently described neoplasms of the sinonasal tract.
Bishop, Justin A
Surgical pathology of the sinonasal region (i.e., nasal cavity and the paranasal sinuses) is notoriously difficult, due in part to the remarkable diversity of neoplasms that may be encountered in this area. In addition, a number of neoplasms have been only recently described in the sinonasal tract, further compounding the difficulty for pathologists who are not yet familiar with them. This manuscript will review the clinicopathologic features of some of the recently described sinonasal tumor types: NUT midline carcinoma, HPV-related carcinoma with adenoid cystic-like features, SMARCB1 (INI-1) deficient sinonasal carcinoma, biphenotypic sinonasal sarcoma, and adamantinoma-like Ewing family tumor.
Echogenic material in the fetal gallbladder in a surviving monochorionic twin.
Sepulveda, W; Stagiannis, K D
Fetal gallstones or echogenic sludge in the fetal gallbladder have rarely been reported prenatally despite the increasing number of ultrasound scans performed during pregnancy. In this report we present a case in which diffuse echogenic material was detected in the fetal gallbladder in a surviving monochorionic twin. This report identifies another predisposing factor for fetal gallstones/sludge in the perinatal period.
Scintigraphic demonstration of acute gastrointestinal bleeding caused by gallbladder carcinoma eroding the colon
Czerniak, A.; Zwas, S.T.; Rabau, M.Y.; Avigad, I.; Borag, B.; Wolfstein, I.
Massive lower gastrointestinal (GI) bleeding caused by gallbladder carcinoma eroding into the colonic wall was demonstrated accurately by Tc-99m RBCs. In addition, retrograde bleeding into the gallbladder was also identified while arteriography did not show contrast extravasation. This case supports the use of Tc-99m RBCs over Tc-99m sulfur colloid for more accurate localization of lower GI bleeding.
Successful Elimination of Ascaris lumbricoides from the Gallbladder by Conservative Medical Therapy.
Misra, Manish Kumar; Singh, Sarabjeet; Bhagat, Tripta Sethi
Migration of Ascaris lumbricoides into the gallbladder is rare, unlike ascariasis of the bile duct and when it does occur, treatment is generally by endoscopic or surgical extraction. We describe a case of the successful treatment of gallbladder ascariasis with conservative therapy.
The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling.
Li, Tingting; Holmstrom, Sam R; Kir, Serkan; Umetani, Michihisa; Schmidt, Daniel R; Kliewer, Steven A; Mangelsdorf, David J
TGR5 is a G protein-coupled bile acid receptor present in brown adipose tissue and intestine, where its agonism increases energy expenditure and lowers blood glucose. Thus, it is an attractive drug target for treating human metabolic disease. However, TGR5 is also highly expressed in gallbladder, where its functions are less well characterized. Here, we demonstrate that TGR5 stimulates the filling of the gallbladder with bile. Gallbladder volume was increased in wild-type but not Tgr5(-/-) mice by administration of either the naturally occurring TGR5 agonist, lithocholic acid, or the synthetic TGR5 agonist, INT-777. These effects were independent of fibroblast growth factor 15, an enteric hormone previously shown to stimulate gallbladder filling. Ex vivo analyses using gallbladder tissue showed that TGR5 activation increased cAMP concentrations and caused smooth muscle relaxation in a TGR5-dependent manner. These data reveal a novel, gallbladder-intrinsic mechanism for regulating gallbladder contractility. They further suggest that TGR5 agonists should be assessed for effects on human gallbladder as they are developed for treating metabolic disease.
Isolated IgG4-related cholecystitis mimicking gallbladder cancer: a case report.
Shin, Sang-Wook; Kim, Yongsoo; Jeong, Woo Kyoung; Kim, Jinoo; Kim, Min Yeong; Oh, Young Ha; Pyo, Ju Yeon
A 58-year-old man with right upper quadrant pain was referred to the radiology department. The patient underwent computed tomography and magnetic resonance imaging, which suggested the diagnosis of gallbladder cancer invading the liver. After surgical removal of the gallbladder, and the adjacent liver parenchyma was performed, the histologic diagnosis of IgG4-related cholecystitis was made.
Study on Salmonella Typhi occurrence in gallbladder of patients suffering from chronic cholelithiasis-a predisposing factor for carcinoma of gallbladder.
Walawalkar, Yogesh D; Gaind, Rajni; Nayak, Vijayashree
Cholelithiasis is frequently associated with carcinoma of gallbladder, and the presence of Salmonella Typhi in gallbladder of patients suffering from cholelithiasis is implicated as a predisposing factor for carcinogenesis. This study was conducted on patients suffering from chronic cholelithiasis from a region in North India-endemic area for enteric fever with high incidence of gallstones and gallbladder cancer. Since culture studies rarely reveal the chronic Salmonella Typhi persistence, we use PCR assay to specifically amplify the H1-d flagellin gene sequence homologous with Salmonella Typhi. Seven cases (17.5%), none of which were positive for culture, showed positive PCR results for Salmonella Typhi, 4 (10%) of which were tissue, 2 bile (5%), and 1 gallstone (2.5%). The chronic existence of Salmonella Typhi in gallbladder disease was confirmed. Thus, the study would indicate the importance of vaccination so as to prevent chronic infection and need for early diagnostic tools to prevent any further complications.
Perforation of the gallbladder: a rare cause of acute abdominal pain.
Ponten, Joep B; Selten, Jasmijn; Puylaert, Julien B C M; Bronkhorst, Maarten W G A
An 82-year-old woman without any previous medical history arrived in the emergency department with severe pain in the entire abdomen since 5 h. Blood tests showed, apart from a CRP of 28 mg/l, no abnormalities. We decided to perform an abdominal ultrasound, which showed an easily compressible gallbladder, containing a small, mobile gallstone and free fluid in the abdomen. During ultrasound-guided punction of this fluid, bile is aspirated. We performed laparoscopy and confirmed a large amount of intraperitoneal bile. Upon inspecting the gallbladder a perforation is seen in the anti-hepatic side of the gallbladder. After performing a cholecystectomy, we opened the gallbladder and detected a dissection-like lesion, which provided access to the peritoneal cavity. The confirmed diagnosis was acute onset free perforation of the gallbladder. The perforation was probably caused by the small obstructing gallstone seen on ultrasound or by another small stone, which could not be visualized.
Extramedullary Plasmacytoma of the Gallbladder Detected on Fluorine 18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Fakhri, Asif Ali; Rodrigue, Paul David; Fakhri, Amena Fatima
Extramedullary plasmacytoma is rare in patients with diagnosed multiple myeloma. Soft tissue plasmacytoma of the gallbladder is particularly uncommon and has been described in only a handful of cases. Diagnosis of gallbladder plasmacytoma with fluorine 18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) has not previously been reported. We present a 65-year-old female with a history of multiple myeloma who underwent a restaging F18-FDG-PET/CT which showed a focal area of hypermetabolic activity, corresponding to a nodular lesion within the posterior gallbladder wall. The patient underwent successful cholecystectomy, with surgical pathology revealing gallbladder plasmacytoma. A follow-up scan was negative for active malignancy. This is a novel case of gallbladder plasmacytoma diagnosed on whole-body F18-FDG PET/CT – thus demonstrating the clinical value of this imaging modality in staging, restaging, and surveillance for patients with multiple myeloma. PMID:27761300
Gallstones play a significant role in Salmonella spp. gallbladder colonization and carriage.
Crawford, Robert W; Rosales-Reyes, Roberto; Ramírez-Aguilar, María de la Luz; Chapa-Azuela, Oscar; Alpuche-Aranda, Celia; Gunn, John S
Salmonella enterica serovar Typhi can colonize the gallbladder and persist in an asymptomatic carrier state that is frequently associated with the presence of gallstones. We have shown that salmonellae form bile-mediated biofilms on human gallstones and cholesterol-coated surfaces in vitro. Here, we test the hypothesis that biofilms on cholesterol gallbladder stones facilitate typhoid carriage in mice and men. Naturally resistant (Nramp1(+/+)) mice fed a lithogenic diet developed cholesterol gallstones that supported biofilm formation during persistent serovar Typhimurium infection and, as a result, demonstrated enhanced fecal shedding and enhanced colonization of gallbladder tissue and bile. In typhoid endemic Mexico City, 5% of enrolled cholelithiasis patients carried serovar Typhi, and bacterial biofilms could be visualized on gallstones from these carriers whereas significant biofilms were not detected on gallstones from Escherichia coli infected gallbladders. These findings offer direct evidence that gallstone biofilms occur in humans and mice, which facilitate gallbladder colonization and shedding.
Clinical experience in appendiceal neuroendocrine neoplasms
Ozcelik, Caglar K.; Bozdogan, Nazan; Dibekoglu, Cengiz
Aim of the study To analyse the incidence of appendiceal neuroendocrine neoplasms in appendectomy specimens and establish the epidemiological and histopathological features, treatment, and clinical course. Material and methods Between 2004 and 2013, 975 patients who underwent appendectomy in Ankara Oncology Education and Research Hospital were retrospectively analysed. Results Neuroendocrine neoplasm was detected in the nine of 975 (0.9%) patients. Neuroendocrine neoplasms were diagnosed in eight patients by appendectomy, which was performed because of the prediagnosis of acute appendicitis, and in one patient by the suspicious mass detection during surgical procedures that were done in the appendix for a different reason. Eight of the patients' tumours were in the tip of the appendix, and one of the patients' tumours was at the base of appendix. Tumour size in 77.8% of patients was equal or less than 1 cm, in 22.2% patients it was 1–2 cm. There was tumour invasion in the muscularis propria layer in four patients, in the serosa layer in three patients, and in the deep mesoappendix in two patients. Patients were followed for a median of 78 months. In the follow-up of patients who were operated because of colon cancer, metachronous colon tumour evolved. This patient died due to progressive disease. Other patients are still disease-free. Conclusions The diagnosis of neuroendocrine neoplasm is often incidentally done after appendectomy. Tumour size is important in determining the extent of disease and in the selection of the surgical method during operation. PMID:26793027
[Viruses as agents inducing cutaneous neoplasms].
Bravo Puccio, Francisco
The oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV). Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the human T-lymphotropic virus type I (HTLV-1), which is responsible for the T-cell lymphomas, in which the cutaneous manifestations are non-specific and have a wide spectrum, thus posing a challenge for differential diagnosis. The Epstein Barr virus, linked to nasal lymphomas of NK/T-cells and Hydroa-like cutaneous lymphomas, is also part of this group. In an era in which the genetic and molecular aspects of cancer research prevail, we may not leave behind the concept of neoplasms as a result an infection with a viral agent, which opens a wide array of new possibilities for cancer treatment based on antiviral drugs.
Neoplasms identified in free-flying birds
Siegfried, L.M.
Nine neoplasms were identified in carcasses of free-flying wild birds received at the National Wildlife Health Laboratory; gross and microscopic descriptions are reported herein. The prevalence of neoplasia in captive and free-flying birds is discussed, and lesions in the present cases are compared with those previously described in mammals and birds.
SNP Array in Hematopoietic Neoplasms: A Review
Song, Jinming; Shao, Haipeng
Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants. PMID:27600067
Presence and distribution of leptin and leptin receptor in the canine gallbladder.
Lee, Sungin; Lee, Aeri; Kweon, Oh-Kyeong; Kim, Wan Hee
The hormone leptin is produced by mature adipocytes and plays an important role in regulating food intake and energy metabolism through its interaction with the leptin receptor. In addition to roles in obesity and obesity-related diseases, leptin has been reported to affect the components and secretion of bile in leptin-deficient mice. Furthermore, gallbladder diseases such as cholelithiasis are known to be associated with serum leptin concentrations in humans. We hypothesized that the canine gallbladder is a source of leptin and that the leptin receptor may be localized in the gallbladder, where it plays a role in regulating the function of this organ. The aim of this study was to demonstrate the presence and expression patterns of leptin and its receptors in normal canine gallbladders using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry. Clinically normal gallbladder tissue samples were obtained from four healthy beagle dogs with similar body condition scores. RT-PCR and sequencing of the amplified PCR products revealed the presence of leptin mRNA and its receptors in the gallbladder. Immunohistochemical investigations demonstrated the expression of leptin and its receptors in the luminal single columnar and tubuloalveolar glandular epithelial cells. In conclusion, the results of this study demonstrated the presence of leptin and its receptors in the gallbladders of dogs. Leptin and its receptor were both localized throughout the cytoplasm of luminal and glandular epithelial cells. These results suggested that the gallbladder is not only a source of leptin, but also a target of leptin though autocrine/paracrine mechanisms. The results of this study could increase the understanding of both the normal physiological functions of the gallbladder and the pathophysiological mechanisms of gallbladder diseases characterized by leptin system dysfunction.
The role of TRPP2 in agonist-induced gallbladder smooth muscle contraction.
Zhong, Xingguo; Fu, Jie; Song, Kai; Xue, Nairui; Gong, Renhua; Sun, Dengqun; Luo, Huilai; He, Wenzhu; Pan, Xiang; Shen, Bing; Du, Juan
TRPP2 channel protein belongs to the superfamily of transient receptor potential (TRP) channels and is widely expressed in various tissues, including smooth muscle in digestive gut. Accumulating evidence has demonstrated that TRPP2 can mediate Ca(2+) release from Ca(2+) stores. However, the functional role of TRPP2 in gallbladder smooth muscle contraction still remains unclear. In this study, we used Ca(2+) imaging and tension measurements to test agonist-induced intracellular Ca(2+) concentration increase and smooth muscle contraction of guinea pig gallbladder, respectively. When TRPP2 protein was knocked down in gallbladder muscle strips from guinea pig, carbachol (CCh)-evoked Ca(2+) release and extracellular Ca(2+) influx were reduced significantly, and gallbladder contractions induced by endothelin 1 and cholecystokinin were suppressed markedly as well. CCh-induced gallbladder contraction was markedly suppressed by pretreatment with U73122, which inhibits phospholipase C to terminate inositol 1,4,5-trisphosphate receptor (IP3) production, and 2-aminoethoxydiphenyl borate (2APB), which inhibits IP3 recepor (IP3R) to abolish IP3R-mediated Ca(2+) release. To confirm the role of Ca(2+) release in CCh-induced gallbladder contraction, we used thapsigargin (TG)-to deplete Ca(2+) stores via inhibiting sarco/endoplasmic reticulum Ca(2+)-ATPase and eliminate the role of store-operated Ca(2+) entry on the CCh-induced gallbladder contraction. Preincubation with 2 μmol L(-1) TG significantly decreased the CCh-induced gallbladder contraction. In addition, pretreatments with U73122, 2APB or TG abolished the difference of the CCh-induced gallbladder contraction between TRPP2 knockdown and control groups. We conclude that TRPP2 mediates Ca(2+) release from intracellular Ca(2+) stores, and has an essential role in agonist-induced gallbladder muscle contraction.
Monolayer and three-dimensional cell culture and living tissue culture of gallbladder epithelium.
Nakanuma, Y; Katayanagi, K; Kawamura, Y; Yoshida, K
Several models for preparing and isolating human and animal gallbladder epithelial cells, including low-grade gallbladder carcinoma cells, as well as proposed systems for culturing these isolated epithelial cells are reviewed here. Several reports concerning tissue culture of the gallbladder are also reviewed. The cell culture systems are divided into monolayer cell culture on collagen-coated or uncoated culture dishes or other culture substrate and three-dimensional cell culture in collagen gel. To prepare and isolate gallbladder epithelial cells, digestion of the gallbladder mucosa, abrasion of the mucosal epithelial cells, and excision of epithelial outgrowth of mucosal explants are applied. In monolayer cell culture, most of the specific biological features of isolated and cultured cells characteristic to the gallbladder are gradually lost after several passages, though quantitative and objective analyses of the pathophysiology of cultured cells and their secretory substances can be performed. Tissue culture using explants of the gallbladder has mainly been used for physiological studies of the gallbladder, such as investigating the transport of water and electrolytes. In this tissue culture system, quantitative assessment is difficult, though the original and specific biological and histological characteristics of the gallbladder are retained. Three-dimensional collagen gel culture could be an ideal model combining monolayer cell culture and tissue culture systems, and create controllable conditions or environments when several biologically active substances, such as growth factors, proinflammatory cytokines and adhesion molecules, are added to the culture medium. Advantages and shortcomings of individual cultivation models are discussed, and selecting the culture model most appropriate to the purpose of the study will facilitate investigations of the biology and pathogenetic mechanisms of gallbladder diseases such as cholelithiasis.
Gallbladder carcinoma - a rare cause of pyloric-duodenal stenosis.
Niculescu, Zizi; Ulmeanu, Victoria; Ghinea, Mihaela Maria; Mocanu, Liliana; Niculescu, Costin; Grigorian, Mircea
Pyloric duodenal stenosis is usually caused by pyloric, juxtapyloric or duodenal ulcer, or by postbulbar ulcer. Gallbladder cancer (GBC), duodenal diverticula, annular pancreas and superior mesenteric artery syndrome (Wilkie's syndrome) are rare causes of pyloric duodenal stenosis. The case of a 66-year-old female patient is presented. The patient was admitted to hospital presenting anorexia, repeated alimentary vomiting, epigastric pain, and weight loss. Objective clinical examination upon admission: clapotage à jeun is present, triggered by tapping the epigastric region. Laboratory tests reveal moderate anemia, hypokalemic alkalosis, increased levels of cholestatic enzymes and of tumor markers. Gastroendoscopy: Stomach presenting stasis fluid in large quantity. Deformed antropyloric region caused by extrinsic compression. Abdominal native magnetic resonance imaging (MRI) and with contrast medium: cholecyst lumen entirely obstructed with calculi; thickened wall, with heterogeneous gadolinophilia; gadolinophilic mass erasing the bordering limit in relation to the cholecyst wall and the colon hepatic angle, and leaving a print on the pyloric region. During surgery, upon opening the peritoneal cavity, a tumoral pericholecystic block was observed, including the pyloric-duodenal region and the transverse mesocolon. Histopathology tests of tissue samples showed adipose conjunctive tissue with invasive adenocarcinoma. Immunohistochemical tests [cytokeratin (CK) 7, CK17, CK19, CK20, CDX2, mucin (MUC) 1, MUC2, MUC5AC, MUC6, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)] were consistent with infiltrating neoplastic carcinoma, originating in the gallbladder epithelium. Gastrointestinal obstruction cases caused by gallbladder carcinoma are rare. The pyloric-duodenal region is more frequently affected, as compared to the small intestine or the colon.
Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience
Gold, Douglas G.; Miller, Robert C. Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.
Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.
Bowel hath no fury like a gallbladder inflamed
Khan, Amad; Flavin, Kathyrn Ellen; Harris, Lauren Sarah; Chaudhry, Mohammad Naushad; Reading, Nicholas
Gallstone ileus is a well-established phenomenon in which a large gallstone leads to mechanical small bowel obstruction. This case, however, reports the novel finding of a patient presenting with suprapubic pain and guarding caused by paralytic ileus of the small bowel and a duodenal perforation secondary to a necrotic gallbladder. It highlights the importance of distinguishing between gallstone ileus and paralytic ileus and how the management of the two conditions differs. Furthermore, this article discusses how paralytic ileus caused by intra-abdominal inflammatory conditions such as cholecystitis can mask the typical clinical findings making the diagnosis difficult. PMID:24876462
[The kinetics of canine gallbladder before and after feeding and cerulein administration].
Romański, Krzysztof; Sławuta, Piotr
In the previous studies in men and dogs, gallbladder contractility, contraction time, initial and residual volumes as well as ejection and refilling fractions have been determined. However, no basic scope of the characteristics of contractile gallbladder activity has been determined and no parameters measured in basic experimental conditions, necessary for this purpose, have been proposed what was the aim of present work. Twenty two experiments were performed on four healthy mongrel dogs weighing 12-16 kg each. Dogs were fasted 18-20 h before start of the experiment. Animals were examined in lying position with the use of apparatus Microimager 2000 M 200 812 with sectorial sound, 3.5 MHz. After control gallbladder measurements, animals were fed with different meals or 30 min infusion of cerulein at the dose 20 ng/kg was started. Four types of meals were used. Meal 1: dry food 300 g + 200 cc of tap water per animal. Meal 2: canned food 300 g + 200 cc of tap water per animal. Meal 3: dry food 100 g + + canned food 200 g + sunflower oil 100 ml per animal. Meal 4: dry food 300 g + canned food 300 g + sunflower oil 30 ml per animal. Ultrasonographical gallbladder imaging was performed in each experiment every 10 min and was continued during 2 hours after stimulus application. Length, width and height of the gallbladder was measured on gallbladder images, then gallbladder volumes were estimated using the method of Dodds and finally, gallbladder kinetic parameters were calculated. Meals 1 and 2 did not evoke statistically significant gallbladder contractions. After meal no. 3 gallbladder significantly contracted, for about 1.5 h. Meal no. 4 caused gallbladder contraction duration of which exceeded time of investigation while maximal strength of contraction was similar to that in response to meal no. 3. Following cerulein infusion, subsequent parameters of gallbladder kinetics, i.e. initial, residual and terminal volumes, ejection and refilling fractions as well as
Role of Gallbladder Mucus Hypersecretion in the Evolution of Cholesterol Gallstones
Lee, Sum P.; Lamont, J. Thomas; Carey, Martin C.
Because mucin glycoproteins may be important in the pathophysiology of gallstones, we studied the relationship among biliary lipids, gallbladder mucin secretion, and gallstone formation in cholesterol-fed prairie dogs. Organ culture studies of gallbladder explants revealed that the incorporation of [3H]glucosamine into tissue and secretory gallbladder glycoproteins was significantly increased at 3, 5, 8, and 14 d of feeding. Peak secretion of labeled mucin occurred at 5 d, when total tissue and secreted glycoprotein production was fivefold greater than control. Gel filtration of the secreted glycoprotein on Sepharose 4B indicated that the majority of radioactivity was present in a macromolecule of > 1 million molecular weight. The increased secretion of gallbladder mucin was organ specific, in that [3H]glucosamine incorporation into glycoproteins of stomach and colon was unaffected by cholesterol feeding. Similarly, the incorporation of [3H]mannose into gallbladder membrane glycoproteins was not altered by cholesterol feeding. The rate of glycoprotein synthesis and secretion returned to normal upon withdrawal of the cholesterol diet, and ligation of the cystic duct before cholesterol feeding prevented gallbladder mucin hypersecretion. Both results indicate that the stimulus to mucin secretion was a constituent of bile. Gallbladder bile after 5 d contained cholesterol in micelles, liquid crystals, and crystals, whereas hepatic bile remained a single micellar phase throughout cholesterol feeding. For this reason the cholesterol-saturation indices of gallbladder bile were compared in both homogenized and centrifuged samples. The micellar phase of gallbladder bile was appreciably less saturated than homogenized bile at 5 and 8 d, which reflects the continuous nucleation of cholesterol in the gallbladder. Purified human gallbladder mucin gels were shown to induce nucleation of lecithin-cholesterol liquid crystals from supersaturated hepatic bile. These in turn gave rise
Filling of the gallbladder as studied by computer-assisted Tc-99m HIDA scintigraphy: concise communication
van der Linden, W.; Kempi, V.
Gallbladder filling was studied using computer-assisted cholescintigraphy in normal subjects who had fasted overnight. The gallbladder tended to visualize earlier than the distal part of the common bile duct. It appeared at approximately the same time regardless of whether or not there was passage of activity into the duodenum. This suggests that filling is not dependent on contraction of the sphincter of Oddi. Sequential images demonstrated that the activity entering the gallbladder rapidly reached the fundus. Time-activity curves showed a gradual buildup of activity in the bile ducts followed by sudden entrance into the gallbladder. Time-activity curves of the gallbladder's proximal and distal parts showed signs of an exchange of activity, suggesting that the gallbladder's motor function is not quiescent during fasting. Gallbladder motility could explain the periodic irregularities on the time-activity curve. These irregularities were smaller but no less frequent after morphine administration.
Intraductal tubular neoplasms of the bile ducts.
Katabi, Nora; Torres, Javiera; Klimstra, David S
Although most tumors of the bile ducts are predominantly invasive, some have an exophytic pattern within the bile ducts; these intraductal papillary neoplasms usually have well-formed papillae at the microscopic level. In this study, however, we describe a novel type of intraductal neoplasm of the bile ducts with a predominantly tubular growth pattern and other distinctive features. Ten cases of biliary intraductal neoplasms with a predominantly tubular architecture were identified in the files of the Pathology Department at Memorial Sloan-Kettering Cancer Center from 1983 to 2006. For each of these cases we studied the clinical presentation, histologic and immunohistochemical features (9 cases only), and the clinical follow-up of the patients. Three male and 7 female patients (38 to 78 y) presented with obstructive jaundice or abdominal pain. Eight of the patients underwent a partial hepatectomy; 2 underwent a laparoscopic bile duct excision, followed by a pancreatoduodenectomy in one of them. The tumors range in size from 0.6 to 8.0 cm. The intraductal portions of the tumors (8 intrahepatic, 1 extrahepatic hilar, 1 common bile duct) were densely cellular and composed of back-to-back tubular glands and solid sheets with minimal papillary architecture. The cells were cuboidal to columnar with mild to moderate cytologic atypia. Foci of necrosis were present in the intraductal component in 6 cases. An extraductal invasive carcinoma component was present in 7 cases, composing <25% of the tumor in 4 cases, and >75% in 1 case. It was observed by immunohistochemical analysis that the tumor cells expressed CK19, CA19-9, MUC1, and MUC6 in most cases and that SMAD4 expression was retained. MUC2, MUC5AC, HepPar1, synaptophysin, chromogranin, p53, and CA125 were negative in all cases and most were negative for CEA-M and B72.3. Four patients were free of tumor recurrence after 7 to 85 months (average, 27 mo). Four patients with an invasive carcinoma component suffered
[The intensive care gallbladder as shock organ: symptoms and therapy].
Rimkus, C; Kalff, J C
Acute acalculous cholecystitis (AAC) represents a severe disease in critically ill patients. The pathogenesis of acute necroinflammatory gallbladder disease is multifactorial and intensive care unit (ICU) patients show multiple risk factors. In addition AAC is difficult to diagnose because of the vague physical and non-specific technical findings. Only the combination of clinical and technical findings including the challenging physical examination of critically ill patients, laboratory results and ultrasound or computed tomography (CT) scan, will lead to the diagnosis. The condition of AAC has a rapid progress to gallbladder necrosis, gangrene and perforation and these complications are reflected in the high morbidity and mortality rates, therefore, therapy should be promptly initiated. If there are no clinical contraindications for an operative approach cholecystectomy is the definitive treatment and both open and laparoscopic procedures have been used. In unstable, critically ill patients percutaneous cholecystostomy should be immediately performed. In addition, transpapillary endoscopic drainage is also possible if there are contraindications for percutaneous cholecystostomy. Patients who fail to improve or deteriorate following interventional drainage should be reconsidered for cholecystectomy. Due to the fact that more than 90 % of patients treated with percutaneous cholecystostomy showed no recurrence of symptoms during a period of more than 1 year, it is still unclear if percutaneous cholecystostomy is the definitive treatment of AAC for unstable patients or if delayed cholecystectomy is still necessary.
Current Role of Minimally Invasive Radical Cholecystectomy for Gallbladder Cancer
Manzoni, Alberto; Guerini, Francesca; Ramera, Marco; Aroldi, Francesca; Zaniboni, Alberto; Rosso, Edoardo
Background. For Tis and T1a gallbladder cancer (GbC), laparoscopic cholecystectomy can provide similar survival outcomes compared to open cholecystectomy. However, for patients affected by resectable T1b or more advanced GbC, open approach radical cholecystectomy (RC), consisting in gallbladder liver bed resection or segment 4b-5 bisegmentectomy, with locoregional lymphadenectomy, is considered the gold standard while minimally invasive RC (MiRC) is skeptically considered. Aim. To analyze current literature on perioperative and oncologic outcomes of MiRC for patients affected by GbC. Methods. A Medline review of published articles until June 2016 concerning MiRC for GbC was performed. Results. Data relevant for this review were presented in 13 articles, including 152 patients undergoing an attempt of MiRC for GbC. No randomized clinical trial was found. The approach was laparoscopic in 147 patients and robotic in five. Conversion was required in 15 (10%) patients. Postoperative complications rate was 10% with no mortality. Long-term survival outcomes were reported by 11 studies, two of them showing similar oncologic results when comparing MiRC with matched open RC. Conclusions. Although randomized clinical trials are still lacking and only descriptive studies reporting on limited number of patients are available, current literature seems suggesting that when performed at highly specialized centers, MiRC for GbC is safe and feasible and has oncologic outcomes comparable to open RC. PMID:27885325
Mucous granule exocytosis and CFTR expression in gallbladder epithelium.
Kuver, R; Klinkspoor, J H; Osborne, W R; Lee, S P
A mechanistic model of mucous granule exocytosis by columnar epithelial cells must take into account the unique physical-chemical properties of mucin glycoproteins and the resultant mucus gel. In particular, any model must explain the intracellular packaging and the kinetics of release of these large, heavily charged species. We studied mucous granule exocytosis in gallbladder epithelium, a model system for mucus secretion by columnar epithelial cells. Mucous granules released mucus by merocrine exocytosis in mouse gallbladder epithelium when examined by transmission electron microscopy. Spherules of secreted mucus larger than intracellular granules were noted on scanning electron microscopy. Electron probe microanalysis demonstrated increased calcium concentrations within mucous granules. Immunofluorescence microscopic studies revealed intracellular colocalization of mucins and the cystic fibrosis transmembrane conductance regulator (CFTR). Confocal laser immunofluorescence microscopy confirmed colocalization. These observations suggest that calcium in mucous secretory granules provides cationic shielding to keep mucus tightly packed. The data also suggests CFTR chloride channels are present in granule membranes. These observations support a model in which influx of chloride ions into the granule disrupts cationic shielding, leading to rapid swelling, exocytosis and hydration of mucus. Such a model explains the physical-chemical mechanisms involved in mucous granule exocytosis.
Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma
Background The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors. PMID:21303542
Evidence-Based Current Surgical Practice: Calculous Gallbladder Disease
Duncan, Casey B.; Riall, Taylor S.
Gallbladder disease is common and, if managed incorrectly, can lead to high rates of morbidity, mortality, and extraneous costs. The most common complications of gallstones include biliary colic, acute cholecystitis, common bile duct stones, and gallstone pancreatitis. Ultrasound is the initial imaging modality of choice. Additional diagnostic and therapeutic studies including computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) are not routinely required but may play a role in specific situations. Biliary colic and acute cholecystitis are best treated with early laparoscopic cholecystectomy. Patients with common bile duct stones should be managed with cholecystectomy, either after or concurrent with endoscopic or surgical relief of obstruction and clearance of stones from the bile duct. Mild gallstone pancreatitis should be treated with cholecystectomy during the initial hospitalization to prevent recurrence. Emerging techniques for cholecystectomy include single-incision laparoscopic surgery (SILS) and natural orifice transluminal endoscopic surgery (NOTES). Early results in highly selected patients demonstrate the safety of these techniques. The management of complications of the gallbladder should be timely and evidence-based, and choice of procedures, particularly for common bile duct stones, is largely influenced by facility and surgeon factors. PMID:22986769
Does bile protect or damage interstitial Cajal-like cells in the human gallbladder?
Pasternak, Artur; Szura, Miroslaw; Matyja, Maciej; Tomaszewski, Krzysztof A; Matyja, Andrzej
the etiology of gallstone disease is considered to be multifactorial, including biliary cholesterol hypersecretion, supersaturation and crystallization, stone formation, bile stasis and mucus hypersecretion and gel formation. Gallbladder hypomotility seems to be a key process that triggers the precipitation of cholesterol microcrystals from supersaturated lithogenic bile. the purpose of the current study was to determine whether ICLCs in the gallbladder were influenced by lithogenic bile. Gallbladder specimens were collected from 30 patients (8 males and 22 females) who underwent elective laparoscopic cholecystectomy for symptomatic gallstone disease. The control group consisted of 25 consecutive patients (11 males and 14 females) who received elective treatment for pancreatic head tumors. ICLCs were visualized in paraffin sections of gallbladders using double immunofluorescence protocol with monoclonal c-kit antibodies and mast cell tryptase. Cholesterol, phospholipid and bile acid concentrations were measured in bile samples obtained by needle aspiration from the gallbladder at the time of surgery. The number of ICLCs in the gallbladder wall was significantly lower in the study group than in the control group (3.35 ± 1.23 vs. 7.06 ± 1.82 cell/FOV in the muscularis propria, P < 0.001) and correlated with a significant increase in the cholesterol saturation index. The glycocholic and taurocholic acid levels were significantly elevated in the control subjects compared with the study group. The results suggest that bile composition may play an important role in the reduction of ICLC density in the gallbladder.
Glucose transporter-1 (GLUT-1) immunoreactivity in benign, premalignant and malignant lesions of the gallbladder.
Legan, Mateja; Tevžič, Spela; Tolar, Ana; Luzar, Boštjan; Marolt, Vera Ferlan
GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, low-grade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0-10% of cells stained), positive with weak to moderate (10-50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.
Histochemistry of glycoconjugates in the gallbladder epithelium of ten animal species.
Madrid, J F; Ballesta, J; Galera, T; Castells, M T; Pérez-Tomás, R
A battery of seven lectins and several conventional mucin histochemical techniques were used to identify the epithelial mucins of the gallbladder of ten species: man, rabbit (Oryctolagus cuniculus, mammalia), hamster (Mesocricetus auratus, mammalia), chicken (Gallus gallus, bird), sparrow (Passer domesticus, bird), moorish gecko (Tarentola mauritanica, reptilia), ladder snake (Elaphe scalaris, reptilia), lake frog (Rana perezi, amphibia), natterjack toad (Bufo calamita, amphibia) and gilthead sea bream (Sparus auratus, fish). Glycogen was found in the epithelial lining of the reptilian and amphibian gallbladders. Sulphate and carboxyl groups were frequently found in the same species, except in the ladder snake and natterjack toad gallbladders where only sulphate groups were identified. Sialic acid residues were detected in man, rabbit, bird, T. mauritanica, R. perezi and fish gallbladders. ConA binding pattern was similar in the ten species studied. In the human gallbladder only PNA failed to label the luminal surface, while the glands were only unreactive to DBA. The human gallbladder showed a large variety of saccharides. The present results suggest that no relation exists between the composition of the gallbladder mucins and the situation of the species in the phylogenetic scale.
Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids.
Erranz, Benjamín; Miquel, Juan Francisco; Argraves, W Scott; Barth, Jeremy L; Pimentel, Fernando; Marzolo, María-Paz
Cholesterol crystal formation in the gallbladder is a key step in gallstone pathogenesis. Gallbladder epithelial cells might prevent luminal gallstone formation through a poorly understood cholesterol absorption process. Genetic studies in mice have highlighted potential gallstone susceptibility alleles, Lith genes, which include the gene for megalin. Megalin, in conjunction with the large peripheral membrane protein cubilin, mediates the endocytosis of numerous ligands, including HDL/apolipoprotein A-I (apoA-I). Although the bile contains apoA-I and several cholesterol-binding megalin ligands, the expression of megalin and cubilin in the gallbladder has not been investigated. Here, we show that both proteins are expressed by human and mouse gallbladder epithelia. In vitro studies using a megalin-expressing cell line showed that lithocholic acid strongly inhibits and cholic and chenodeoxycholic acids increase megalin expression. The effects of bile acids (BAs) were also demonstrated in vivo, analyzing gallbladder levels of megalin and cubilin from mice fed with different BAs. The BA effects could be mediated by the farnesoid X receptor, expressed in the gallbladder. Megalin protein was also strongly increased after feeding a lithogenic diet. These results indicate a physiological role for megalin and cubilin in the gallbladder and provide support for a role for megalin in gallstone pathogenesis.
Are left-sided gallbladders really located on the left side?
Nagai, M; Kubota, K; Kawasaki, S; Takayama, T; BandaiY; Makuuchi, M
OBJECTIVE: The aim of this investigation was to establish the association between left-sided gallbladders and right-sided round ligaments. SUMMARY BACKGROUND DATA: The left-sided gallbladder is a rare anomaly and has been classified into two types: 1) gallbladder migration to the left side and 2) development of a second gallbladder with atrophy of the original one. Recently, left-sided gallbladders were reported to be associated with right-sided round ligaments. METHODS: The authors reviewed 3 patients treated in their departments and 15 patients reported in the literature diagnosed as having left-sided gallbladders accompanied by right-sided round ligaments. RESULTS: Although the gallbladders of all 18 patients were located at the normal site, they were diagnosed as being left sided because of the right-sided round ligaments. This anomaly was accompanied by abnormal intrahepatic portal venous branching, which could be classified into two types. In eight patients, the first branch of the portal vein ran to the posterior segment and then the portal vein formed a trunk of the left and right anterior portal veins. The latter portal vein formed the umbilical portion and finally joined the right-sided round ligament (trifurcation type). In five, the portal vein diverged normally to form the left and right portal veins, then the latter branched to form the anterior and posterior segments, and finally the anterior branch joined the round ligament (bifurcation type). In the other five, the branching type could not be determined. CONCLUSIONS: A right-sided round ligament causes a gallbladder at the normal site to be located on the left side. This anomaly should not be diagnosed as a left-sided gallbladder but as a right-sided round ligament. Recognition of this anomaly clinically is important when performing hepatectomy, because it is always associated with abnormal intrahepatic portal venous branching. Images Figure 1. Figure 2. Figure 3. Figure 4. PMID:9060583
Intrathoracic neoplasms in the dog and cat
Weller, R.E.
Very little is known regarding the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in companion animals. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms. Most studies of thoracic neoplasia have focused on the pathology of primary and metastatic neoplasms of the lung with little attention given to diagnostic and therapeutic considerations. Although the cited incidence rate for primary respiratory tract neoplasia is low, 8.5 cases per 100,000 dogs and 5.5 cases per 100,000 cats, intrathoracic masses often attract attention out of proportion to their actual importance since they are often readily visualized on routine thoracic radiographs.
[Gastroenteropancreatic neuroendocrine neoplasms: concepts and related issues].
Lai, Maode
The incidence of neuroendocrine neoplasms (NENs) has been gradually increasing and most of NENs are located in gastroenteropancreatic system. With the application of target therapeutic drugs in recent years, the precise pathological diagnosis is required critically for effective clinical treatment: target therapy needs targeted pathological diagnosis. In this article, the definition of NENs, and the century-long evolution of diagnostic terms and grades are reviewed. The eight steps of pathological diagnosis of NENs for clinical needs are described. Four inconsistent concepts in NENs diagnosis are also discussed, that is immunohistochemical biomarkers of pathological diagnosis, subpopulation of neuroendocrine neoplasms with high proliferative activity, general adenocarcinomas with neuroendocrine differentiation and molecular genetics characteristics. To correctly understand these issues would be of great value for diagnosis and treatment of NENs.
Cholecystocolic fistula caused by gallbladder carcinoma: preoperatively misdiagnosed as hepatic colon carcinoma.
Ha, Gi Won; Lee, Min Ro; Kim, Jong Hun
Cholecystocolic fistula secondary to gallbladder carcinoma is extremely rare and has been reported in very few studies. Most cholecystocolic fistulae are late complications of gallstone disease, but can also develop following carcinoma of the gallbladder when the necrotic tumor penetrates into the adjacent colon. Although no currently available imaging technique has shown great accuracy in recognizing cholecystocolic fistula, abdominopelvic computed tomography may show fistulous communication and anatomical details. Herein we report an unusual case of cholecystocolic fistula caused by gallbladder carcinoma, which was preoperatively misdiagnosed as hepatic flexure colon carcinoma.
Colorectal Liver Metastasis, Primary Gallbladder Carcinoma and Myelofibrosis Present Simultaneously in a Liver Resection Specimen
Gray, Sophie A.; Raber, Menno H.; Provoost, Esther; Toes, Gert-Jan; Klaase, Joost M.
Myelofibrosis and gallbladder carcinoma are both very rare diseases. This case report describes a patient with a history of myelofibrosis and colorectal carcinoma who was diagnosed with colorectal liver metastases. Surgery was performed to remove the metastases, and on site, the gallbladder was removed because of involvement in one of the liver lesions. After pathological examination, a primary gallbladder carcinoma and myelofibrosis were found in addition to the liver metastases. The combination of diseases was not likely to be interconnected but rather an unlucky course of events for the patient. PMID:26600770
A multigenic approach to evaluate genetic variants of PLCE1, LXRs, MMPs, TIMP, and CYP genes in gallbladder cancer predisposition.
Sharma, Kiran Lata; Rai, Rajani; Srivastava, Anshika; Sharma, Aarti; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj
Gallbladder cancer (GBC) is a violent neoplasm associated with late diagnosis, unsatisfactory treatment, and poor prognosis. The disease shows complex interplay between multiple genetic variants. We analyzed 15 polymorphisms in nine genes involved in various pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were matrix metalloproteinases (MMP-2, MMP-7, and MMP-9), tissue inhibitor of metalloproteinases (TIMP-2), cytochrome P450 (CYP)1A1, CYP1B1, phospholipase C epsilon 1 (PLCE1), liver X receptor (LXR)-alpha, and LXR-beta. Genotypes were determined by PCR-RFLP and TaqMan probes. Statistical analysis was done by SPSS version 16. Multilocus analysis was performed by Classification and Regression Tree (CART) analysis and multifactor dimensionality reduction (MDR) to gene-gene interactions in modifying GBC risk. In silico analysis was done using various bioinformatics tools (F-SNP, FAST-SNP). Single locus analysis showed association of MMP-2 (-735 C > T, -1306 C > T), MMP-7 - 181 A > G, MMP-9 (P574R, R668Q), TIMP-2 - 418 G > C, CYP1A1-MspI, CYP1A1-Ile462Val, PLCE1 (rs2274223 A > G, rs7922612 T > C) and LXR-beta T > C (rs3546355 G > A, rs2695121 T > C) polymorphisms with GBC risk (p < 0.05) whereas CYP1B1 and LXR-α variants were not associated with GBC risk. Multidimensional reduction analysis revealed LXR-β (rs3546355 G > A, rs2695121 T > C), MMP-2 (-1306 C > T), MMP-9 (R668Q), and PLCE1 rs2274223 A > G to be key players in GBC causation (p < 0.001, CVC = 7/10). The results were further supported by independent CART analysis (p < 0.001). In silico analysis of associated variants suggested change in splicing or transcriptional regulation. Interactome and STRING analysis showed network of associated genes. The study found PLCE1 and LXR-β network interactions as important contributory factors for genetic predisposition in gallbladder
Presence of Helicobacter spp. DNA in the gallbladder of Egyptian patients with gallstone diseases.
Ghazal, A; El Sabbagh, N; El Riwini, M
Earlier reports on the detection of Helicobacter DNA in the gallbladder tissue of patients with biliary diseases have shown discordant results. This study aimed to detect the presence of Helicobacter in gallstone, gallbladder tissue and bile specimens from subjects with H. pylori-positive gastritis with cholelithiasis. The presence of H. pylori in antrum biopsies was confirmed by rapid urease test and/or histopathological examination. DNA was extracted from gallbladder, bile and gallstone samples from 50 patients undergoing cholecystectomy. The presence of Helicobacter genus-specific DNA (16S rRNA genes) was determined by nested polymerase chain reaction assay. Helicobacter DNA was detected in the gallbladder tissue and bile of 28% and 18% respectively of the patients, but was not detected in any of the gallstones. These results do not rule out the possibility of Helicobacter infection as a contributing agent or cofactor in the development of biliary diseases.
Hepatobiliary scan with delayed gallbladder visualization in a case of acute appendicitis
Smathers, R.L.; Harman, P.K.; Wanebo, H.J.; Read, M.E.
A 40-year-old woman presented with acute epigastric pain with vomiting. Within 24 hours, the pain spread to the right periumbilical region. /sup 99m/Tc disofenin hepatobiliary scan failed to demonstrate the gallbladder on a 60-minute view. The presumative diagnosis of acute cholecystitis was thought to be confirmed on this basis by the patient's physicians. However, a 75-minute view demonstrated filling of the gallbladder. In hepatobiliary scanning for acute abdominal pain, delayed views (2 to 24 hours) are recommended when the gallbladder is not visualized on the 60-minute view. If the gallbladder is visualized, cystic duct obstruction can be excluded and diagnoses such as pancreatitis, acalculous cholecystitis, and acute appendicitis should be investigated.
Primary Gallbladder Lymphoma in a Male Patient with No Risk Factors Detected Incidentally by CT Colonography
Karia, Monil; Mitsopoulos, Grigorios; Patel, Ketan; Rafique, Akkib; Sheth, Hemant
Primary gallbladder lymphoma, although rare, usually presents in females with symptoms mimicking cholecystitis. We present a rare case of primary gallbladder in an 81-year-old male with no risk factors whose only symptom was weight loss. Routine blood tests including liver function tests were unremarkable. A CT colonography was carried out to exclude colonic malignancy. Unilateral gallbladder wall thickening and lymphadenopathy were incidentally detected and confirmed by ultrasound and a decision for the patient to undergo laparoscopic cholecystectomy and intraoperative cholangiogram was made. Histology confirmed extranodal marginal zone lymphoma with follow-up staging and biopsy of the bone marrow not demonstrating spread. Cholecystectomy was therefore deemed curative and no adjuvant therapy was necessary. Thickening of the gallbladder wall on any imaging with or without symptoms should not be ignored or assumed to be cholecystitis, even in males with no risk factors. In these patients urgent cholecystectomy with intraoperative cholangiogram is indicated with histology and haematology follow-up. PMID:26587306
Cholecystokinin-Assisted Hydrodissection of the Gallbladder Fossa during FDG PET/CT-guided Liver Ablation
Tewari, Sanjit O.; Petre, Elena N.; Osborne, Joseph; Sofocleous, Constantinos T.
A 68-year-old female with colorectal cancer developed a metachronous isolated fluorodeoxyglucose-avid (FDG-avid) segment 5/6 gallbladder fossa hepatic lesion and was referred for percutaneous ablation. Pre-procedure computed tomography (CT) images demonstrated a distended gallbladder abutting the segment 5/6 hepatic metastasis. In order to perform ablation with clear margins and avoid direct puncture and aspiration of the gallbladder, cholecystokinin was administered intravenously to stimulate gallbladder contraction before hydrodissection. Subsequently, the lesion was ablated successfully with sufficient margins, of greater than 1.0 cm, using microwave with ultrasound and FDG PET/CT guidance. The patient tolerated the procedure very well and was discharged home the next day.
Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas.
Ishak, Geraldo; Leal, Mariana Ferreira; Dos Santos, Ney Pereira Carneiro; Demachki, Samia; Nunes, Caroline Aquino Moreira; do Nascimento Borges, Barbara; Calcagno, Danielle Queiroz; Smith, Marília Cardoso; Assumpção, Paulo Pimentel; Burbano, Rommel Rodríguez
Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether MYC may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples (p = 0.002, p = 0.046, respectively). Gain of copies of the MYC and TP53 genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively. MYC and TP53 amplifications were associated with immunoreactivity of their protein (p = 0.029, p = 0.001, respectively). MYC hypomethylation was only detected in tumoral samples and was associated with its protein expression (p = 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors (p = 0.019) and with MYC expression (p = 0.044). Moreover, two tumors presented a pathogenic mutation in MYC exon 2 (rs28933407). Our study highlights that the gain of MYC and TP53 copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at MYC may contribute to overexpression of its protein in this type of cancer.
EGFR Expression in Gallbladder Carcinoma in North America
Kaufman, Matthew; Mehrotra, Bhoomi; Limaye, Sewanti; White, Sherrie; Fuchs, Alexander; Lebowicz, Yehuda; Nissel-Horowitz, Sandy; Thomas, Adrienne
BACKGROUND: Increased epidermal growth factor receptor (EGF receptor) expression has been noted in various cancers and has become a useful target for therapeutic interventions. Small studies from Asia and Australia have demonstrated EGFR over-expression in gallbladder cancer. We sought to evaluate the expression of EGFR in a series of 16 gallbladder cancer patients from North America. METHODS: Using tumor registry data, we identified 16 patients diagnosed with gall bladder carcinoma at our medical center between the years of 1998 and 2005. We performed a retrospective review of these patients' charts, obtained cell blocks from pathology archives and stained for EGFR and Her2/neu. RESULTS: Fifteen of sixteen patients were noted to over-express EGFR. Three were determined 1+, nine were 2+ and three were 3+. Eight patients had poorly differentiated adenocarcinoma, six had moderately differentiated and two had well-differentiated tumors. In this small series, there was a trend toward shorter survival and more poorly differentiated tumors in patients with greater intensity of EGFR expression. One patient was EGFR negative but 3+ for erb-2/Her 2-neu expression. No patient co-expressed EGFR and Her-2-neu. Median survival of patients in this series was 17 months. CONCLUSION: In view of our observations confirming the over-expression of EGFR in our patient population in North America, and the recent success of EGFR targeted therapies in other solid tumors that over-express EGFR, it may now be appropriate to evaluate agents targeting this pathway either as single agents or in combination with standard chemotherapy. PMID:18825277
Testosterone and dihydrotestosterone inhibit gallbladder motility through multiple signalling pathways.
Kline, Loren W; Karpinski, Edward
Testosterone (T) has been shown to cause vasodilation in rabbit coronary arteries through a nongenomic pathway. Part of this T-induced relaxation was shown to be mediated by opening voltage dependent K(+) channels. T infusion also reduces peripheral resistance in human males with heart failure. The effects of T or its active metabolite 5-alpha dihydrotestosterone (DHT) are not well studied. This study investigates the effect of T and DHT on contraction in guinea pig gallbladder strips. T or DHT induced a concentration-dependent relaxation of cholecystokinin octapeptide (CCK)-induced tension. Pretreatment of the strips with PKA inhibitor 14-22 amide myristolated had no significant effect on the relaxation induced by either T or DHT. Pretreatment of strips with 2-APB, an inhibitor of IP(3) induced Ca(2+) release, produced a significant (p<0.001) reduction in the T- or DHT-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl(-) when used in combination had no significant effect on the amount of CCK-induced tension, but significantly (p<0.01) decreased the amount of T- or DHT-induced relaxation. The flavone chrysin, an aromatase inhibitor, and genistein, an isoflavone, each produced a significant (p<0.01) reduction in CCK-induced tension. Chrysin significantly (p<0.05) increased T-induced relaxation; however, genistein had no effect on T-induced relaxation. It is concluded that T and DHT inhibits gallbladder motility rapidly by nongenomic actions of the hormones. Multiple pathways that include inhibition of intracellular Ca(2+) release, inhibition of extracellular Ca(2+) entry, and the actions of PKC may mediate this effect.
High DBC1 (CCAR2) expression in gallbladder carcinoma is associated with favorable clinicopathological factors.
Won, Kyu Yeoun; Cho, Hyuck; Kim, Gou Young; Lim, Sung-Jig; Bae, Go Eun; Lim, Jun Uk; Sung, Ji-Youn; Park, Yong-Koo; Kim, Youn Wha; Lee, Juhie
There have been several studies on gallbladder carcinogenesis, and mutations of the KRAS, TP53, and CDKN2A genes have been reported in gallbladder carcinoma. The DBC1 gene (deleted in breast cancer 1) was initially cloned from region 8p21, which was homozygously deleted in breast cancer. DBC1 has been implicated in cancer cell proliferation and death. The functional role of DBC1 in normal cells and the role of DBC1 loss in cancer are not entirely clear. And DBC1 expression and its clinical implications in gallbladder carcinoma have yet to be thoroughly elucidated. Therefore, we evaluated DBC1 expression in 104 gallbladder carcinoma tissues in relation to survival and other prognostic factors via immunohistochemical analysis. DBC1 expression was divided into two categories: high DBC1 expression was observed in 32/104 cases (30.8%) and low expression in 72/104 cases (69.2%). High DBC1 expression correlated significantly with favorable clinicopathologic variables. Furthermore, in survival analysis, the high-DBC1 expression group showed a better survival rate compared to the low-DBC1 expression group. In conclusion, high DBC1 expression is associated with several favorable clinicopathologic factors in gallbladder carcinoma. These findings suggest that loss of DBC1 expression plays a role in tumorigenesis and tumor progression in gallbladder carcinoma.
Effect of increasing oral doses of loperamide on gallbladder motility in man.
Hopman, W P; Rosenbusch, G; Jansen, J B; Lamers, C B
1. Loperamide, a peripherally acting opiate receptor agonist with antidiarrhoeal action, inhibits ileal and colonic motor function. To determine the effect of loperamide on gallbladder motility, we have pretreated five healthy volunteers with 2 mg oral loperamide 24 h, 20, 12 and 2.5 h before; six healthy volunteers with 16 mg oral loperamide 2.5 h before; and eight healthy volunteers with 16 mg oral loperamide 12 and 2.5 h before intravenous infusion of a 'physiological dose' of 12.5 pmol kg-1 cholecystokinin (CCK) for 1 h to stimulate gallbladder contraction. All subjects served as their own controls. Gallbladder volume was measured by ultrasonography and plasma CCK by radioimmunoassay until 90 min after start of the CCK infusion. 2. Infusion of CCK resulted in plasma CCK concentrations similar to those after intraduodenal fat. Integrated gallbladder contraction after 4 X 2 mg loperamide (4600 +/- 891% min) was similar to that without pretreatment (5270 +/- 1037% min; NS). Integrated gallbladder contraction after 1 X 16 mg loperamide diminished from 5458 +/- 412% min without to 2632 +/- 816% min with loperamide (P less than 0.05), and was completely abolished to -596 +/- 762% min (P less than 0.0005 vs without loperamide) after 2 X 16 mg loperamide. 3. It is concluded that loperamide inhibits gallbladder contraction in response to a physiological dose of cholecystokinin in a dose-dependent manner. PMID:2297461
[Gallbladder contractility in early stages of lithogenesis in the lithogenic fed guinea pig].
Lange, K; Gottschalk, M
The main aim of our study was the investigation of gallbladder motility prior to gallstone formation in vivo in guinea pigs fed a lithogenic diet. In a first experiment guinea pigs were fed a lithogenic diet for 5, 15, 30 and 45 days. First gallstones (pigment calculi) appeared after 30 days diet application. The in vitro contractility after lithogenic diet remained unchanged. In a second experimental part the in vivo gallbladder contractility was measured in two experimental animal groups (control group and 21 days lithogenic fed guinea pigs). The isovolumetric pressure rise inside the gallbladder following the intravenous injection of 10(-9) mol/kg body weight ceruletid was the essential contractility parameter (intraluminal basal pressure 5 mm hg). Due to lithogenic feeding of 21 days--that means prior to gallstone formation--the isovolumetric pressure rise was significantly elevated (p < 0.01). Moreover we observed passive distensibility changes of gallbladder muscle due to muscular hyperplasia. The main result of this investigation is the fact that gallbladder muscle in guinea pigs fed a lithogenic diet response to ceruletid application with hypercontractility prior to provable pigment gallstone formation. However gallbladder hypomotility--believed to be a causal factor in cholelithogenesis--was not observed in our experimental conditions.
Melatonin treatment reverts age-related changes in Guinea pig gallbladder neuromuscular transmission and contractility.
Gomez-Pinilla, Pedro J; Camello-Almaraz, Cristina; Moreno, Rosario; Camello, Pedro J; Pozo, María J
The incidence of gallbladder illness increases with age, but the altered mechanisms leading to gallbladder dysfunction are poorly understood. Here we determine the age-related alterations in gallbladder contractility and the impact of melatonin treatment. Isometric tension changes in response to electrical field stimulation and to agonists were recorded from guinea pig gallbladder muscle strips. [Ca(2+)](i) was determined by epifluorescence microscopy in fura-2 loaded isolated gallbladder smooth muscle cells, and F-actin content was quantified by confocal microscopy. Aging reduced neurogenic contractions, which was associated with the impairment of nitrergic innervation and with increased responsiveness of capsaicin-sensitive relaxant nerves, possibly involving calcitonin gene-related peptide. Melatonin treatment for 4 weeks restored neurogenic responses to normal values, with an associated recovery of nitrergic function and the disappearance of the capsaicin-sensitive component. Aging also reduced the contractile responses to cholecystokinin and Ca(2+) influx. The impaired contractility only correlated with diminished Ca(2+) mobilization in response to activation of Ca(2+) influx. Melatonin improved contractility and increased smooth muscle F-actin content without changing Ca(2+) homeostasis. In conclusion, aging impairs gallbladder function as the result of changes in the inhibitory neuromodulation of smooth muscle contractility and the reduction in the myogenic response to contractile agonists. Impaired contractility seems to be related to decreased Ca(2+) influx and damage of contractile proteins. Melatonin significantly ameliorated these age-related changes.
Anatomical and neuropeptidergic properties of the duodenal neurons projecting to the gallbladder in the golden hamster.
Seo, Je Hoon; Cho, Sa Sun; Lee, In Se; Lee, Heungshik S
This study investigated the anatomical and neuropeptidergic properties of the duodenal neurons projecting to the gallbladder in the golden hamster. Fast blue (FB) was injected into the subserosa of the gallbladder in order to identify by retrograde tracing the duodenal neurons that project to the gallbladder. Subsequently, immunofluorescence microscopy was employed to see whether these duodenal neurons contained putative peptidergic neurotransmitters such as calcitonin gene-related peptide (CGRP), galanin (GAL) and vasoactive intestinal polypeptide (VIP). The FB-labeled cells were only found in the duodenal region adjacent to the major duodenal papilla where the biliary duct opens. On the other hand, there was no difference within this duodenal region in the numbers of FB-labeled cells between the mesenteric and antimesenteric portions, suggesting that these two portions of the duodenum equally contribute neuronal projections to the gallbladder. Double-immunofluorescence microscopy clearly demonstrated that a small population of FB-positive duodenal neurons contained putative neurotransmitters CGRP, GAL and VIP. Our data suggest that duodenal neurons around the major duodenal papilla in the golden hamster project to the gallbladder and exert their influence on the gallbladder via neuropeptides such as CGRP, GAL and VIP.
Prevalence of gallstones and gallbladder disease in Canadian Micmac Indian women.
Williams, C N; Johnston, J L; Weldon, K L
The prevalence of gallstones and gallbladder disease was studied between October 1973 and June 1976 in Canadian Micmac Indian women aged 15 to 50 years in an inland rural community near Shubenacadie, NS. Of 132 women at risk 98 underwent cholecystography, 6 had a history of cholecystectomy (verified from hospital records) and 3 had cholecystectomy because of cholecystitis during the 3 years of the study. Of the 17 abnormal cholecystograms 10 showed radiolucent gallstones, and repeated studies documented gallstones in 6 of the 7 radiographs on which the gallbladder was not visualized. The prevalence of gallstones was found to be 211/1000, and that of gallbladder disease, 240/1000. The peak prevalence was at 30 to 39 years of age. The women with gallbladder disease were significantly more obese and of greater parity than those without gallbladder disease even when age was controlled. The Micmac Indian women of Nova Scotia appear to be at a much higher risk for the development of cholesterol gallstones and gallbladder disease than Caucasian women in Framingham, Massachusetts.
Prevalence of gallstones and gallbladder disease in Canadian Micmac Indian women.
Williams, C. N.; Johnston, J. L.; Weldon, K. L.
The prevalence of gallstones and gallbladder disease was studied between October 1973 and June 1976 in Canadian Micmac Indian women aged 15 to 50 years in an inland rural community near Shubenacadie, NS. Of 132 women at risk 98 underwent cholecystography, 6 had a history of cholecystectomy (verified from hospital records) and 3 had cholecystectomy because of cholecystitis during the 3 years of the study. Of the 17 abnormal cholecystograms 10 showed radiolucent gallstones, and repeated studies documented gallstones in 6 of the 7 radiographs on which the gallbladder was not visualized. The prevalence of gallstones was found to be 211/1000, and that of gallbladder disease, 240/1000. The peak prevalence was at 30 to 39 years of age. The women with gallbladder disease were significantly more obese and of greater parity than those without gallbladder disease even when age was controlled. The Micmac Indian women of Nova Scotia appear to be at a much higher risk for the development of cholesterol gallstones and gallbladder disease than Caucasian women in Framingham, Massachusetts. PMID:907946
Ectopic liver and gallbladder in a cloned dog: Possible nonheritable anomaly.
Kim, Min Jung; Kang, Sang Chul; Kim, Jae Hwan; Oh, Hyun Ju; Kim, Geon A; Jo, Young Kwang; Choi, Jin; Kim, Hyunil; Lee, Yeon Hea; Yoo, Ji Min; Eom, Ki Dong; Lee, Byeong Chun
Ectopic liver and gallbladder are rare anomalies usually not accompanied by any symptoms and are found during surgical exploration or autopsy. We aimed to find a cause of this anomaly using somatic cell nuclear transfer (SCNT) technology, which can produce genetically identical organisms. A cloned beagle having ectopic organs was produced and died on the day of birth. Major and ectopic organs were fixed and underwent histologic analysis. SCNT was performed using cells derived from the dead puppy to produce reclones. Normality of internal organs in the original donor dog and recloned dogs was evaluated by computed tomography. While a liver without the gallbladder was located in the abdominal cavity of the cloned dog, a well-defined, reddish brown mass with a small sac was also positioned outside of the thoracic cavity. Histologically, they presented as normal liver and gallbladder. Five reclones were produced, and computed tomography results revealed that the original donor dog and reclones had normal liver and gallbladder structure and location. This is the first report of both ectopic liver and gallbladder in an organism and investigation on the etiology of these abnormalities. Normal organ structure and position in the original donor dog and reclones suggests that the ectopic liver and gallbladder is a possible nonheritable anomaly.
Measurement of gallbladder volume and dynamics by combined SPECT and planar scintigraphy.
Brown, P H; Krishnamurthy, G T; Brar, H S; Gray, L H; Gilbert, S
A new method is described for measurement of gallbladder volume based on three-dimensional single photon emission computed tomography (SPECT). The technique was first validated in a body phantom that used a balloon to represent the gallbladder. The balloon was inflated with a known volume and SPECT volume was calculated by summing the voxels in each transaxial slice above a percentage count threshold. The SPECT and true volume showed a high linear correlation between 15 to 90 ml (r = 0.99). The mean fasting gallbladder volume using a technetium-99m-labelled hepatobiliary agent in nine normal subjects was 26 +/- 2 ml (range 18 to 39 ml). By combining the SPECT measurement with a planar technique, it was also possible to evaluate gallbladder emptying parameters. Following a 3 min infusion of 10 ng kg-1 of cholecystokinin octapeptide (CCK), the mean gallbladder ejection rate was 1.2 +/- 0.2 ml min-1 and the residual volume was 12 +/- 2 ml. SPECT offers a new noninvasive method for accurate measurement of gallbladder volume.
Spontaneous passage of glass beads from the canine gallbladder: facilitation by sphincterotomy.
Hutton, S W; Sievert, C E; Vennes, J A; Shafer, R B; Duane, W C
To investigate the mechanism by which ablation of the sphincter of Oddi prevents gallstone formation, we assessed passage of glass beads out of the gallbladders of dogs with sphincterotomy and sham sphincterotomy. One month after bead implantation, dogs with an intact sphincter passed 52%, 26%, 22%, 10%, 0%, and 0% of beads with diameters of 2, 3, 4, 5, 6, and 8 mm, respectively. For the same respective bead diameters, dogs with a sphincterotomy passed 90%, 90%, 88%, 75%, 75%, and 42% of beads (p less than 0.05 for all bead diameters). No beads were in the common bile duct of any dog. In separate dogs studied by cholescintigraphy, sphincterotomy significantly increased gallbladder ejection fraction from 0.46 to 0.76 (p less than 0.01). In addition, sphincterotomy significantly lowered resting gallbladder volume from 24.4 to 15.8 ml (p less than 0.025) and lowered cholecystokinin-stimulated gallbladder volume from 13.3 to 5.9 ml (p less than 0.025). These data indicate that even with an intact sphincter, small solids can pass from the gallbladder and into the duodenum. Sphincterotomy facilitates passage of solids, apparently by general improvement in gallbladder emptying. Facilitated passage of crystals, microliths, or small stones seems the most likely explanation for prevention of gallstone formation by sphincterotomy.
Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery
Adult Cholangiocarcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Hilar Cholangiocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma; Recurrent Childhood Liver Cancer; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Stage II Gallbladder Cancer; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Childhood Hepatocellular Carcinoma; Stage IV Distal Bile Duct Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Carcinoma
BRCC3 mutations in myeloid neoplasms
Huang, Dayong; Nagata, Yasunobu; Grossmann, Vera; Radivoyevitch, Tomas; Okuno, Yusuke; Nagae, Genta; Hosono, Naoko; Schnittger, Susanne; Sanada, Masashi; Przychodzen, Bartlomiej; Kon, Ayana; Polprasert, Chantana; Shen, Wenyi; Clemente, Michael J.; Phillips, James G.; Alpermann, Tamara; Yoshida, Kenichi; Nadarajah, Niroshan; Sekeres, Mikkael A.; Oakley, Kevin; Nguyen, Nhu; Shiraishi, Yuichi; Shiozawa, Yusuke; Chiba, Kenichi; Tanaka, Hiroko; Koeffler, H. Phillip; Klein, Hans-Ulrich; Dugas, Martin; Aburatani, Hiroyuki; Miyano, Satoru; Haferlach, Claudia; Kern, Wolfgang; Haferlach, Torsten; Du, Yang; Ogawa, Seishi; Makishima, Hideki
Next generation sequencing technologies have provided insights into the molecular heterogeneity of various myeloid neoplasms, revealing previously unknown somatic genetic events. In our cohort of 1444 cases analyzed by next generation sequencing, somatic mutations in the gene BRCA1-BRCA2-containing complex 3 (BRCC3) were identified in 28 cases (1.9%). BRCC3 is a member of the JAMM/MPN+ family of zinc metalloproteases capable of cleaving Lys-63 linked polyubiquitin chains, and is implicated in DNA repair. The mutations were located throughout its coding region. The average variant allelic frequency of BRCC3 mutations was 30.1%, and by a serial sample analysis at two different time points a BRCC3 mutation was already identified in the initial stage of a myelodysplastic syndrome. BRCC3 mutations commonly occurred in nonsense (n=12), frameshift (n=4), and splice site (n=5) configurations. Due to the marginal male dominance (odds ratio; 2.00, 0.84–4.73) of BRCC3 mutations, the majority of mutations (n=23; 82%) were hemizygous. Phenotypically, BRCC3 mutations were frequently observed in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms and associated with -Y abnormality (odds ratio; 3.70, 1.25–11.0). Clinically, BRCC3 mutations were also related to higher age (P=0.01), although prognosis was not affected. Knockdown of Brcc3 gene expression in murine bone marrow lineage negative, Sca1 positive, c-kit positive cells resulted in 2-fold more colony formation and modest differentiation defect. Thus, BRCC3 likely plays a role as tumor-associated gene in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. PMID:26001790
Rectal neuroendocrine neoplasms: a case report
Su, Hao
The gastrointestinal neuroendocrine neoplasms (GI-NENs) are very rare, among which second most common type is the rectal NENs in China. Patients with rectal NENs may experience non-specific symptoms such as pain, perianal bulge, anemia, and bloody stools, and surgery is considered as the first treatment for rectal NENs. We report a case of rectal NENs in a 68-year-old male patient with bloody stools, who received surgery and postoperative pathology revealed an elevated well-differentiated neuroendocrine carcinoma. PMID:28138616
Spectrum and Classification of Cystic Neoplasms of the Pancreas.
Greer, Jonathan B; Ferrone, Cristina R
As patients are living longer and axial imaging is more widespread, increasing numbers of cystic neoplasms of the pancreas are found. Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common. The revised Sendai guidelines provide a safe algorithm for expectant management of certain cystic neoplasms; however, studies are ongoing to identify further subgroups that can be treated nonoperatively. For those patients with high-risk clinical features or symptoms, surgical resection can be performed safely at high-volume pancreatic centers. Accurate diagnosis is critical for accurate decision making.
Fatal intra-abdominal hemorrhage as a result of avulsion of the gallbladder: a postmortem case report
Usui, Akihito; Kawasumi, Yusuke; Hosokai, Yoshiyuki; Saito, Haruo; Igari, Yui; Funayama, Masato
Gallbladder injuries are extremely rare in blunt trauma, with a reported incidence of <2%. We report an autopsy case of fatal hemorrhagic shock due to intra-abdominal bleeding resulting from complete avulsion of the gallbladder associated with liver cirrhosis. Multiplanar images derived from multislice computed tomography (MSCT) performed as part of pre-autopsy screening showed complete avulsion of the gallbladder without any other associated intra-abdominal injuries, facilitating forensic autopsy planning. In this report, we discuss the role of MSCT in cases of fatal intra-abdominal bleeding caused by avulsion of the gallbladder and discuss the mechanism of this injury. PMID:23986858
Malignant neoplasms of the head and neck.
Dickson, Paxton V; Davidoff, Andrew M
Head and neck masses represent a common clinical entity in children. In general, these masses are classified as developmental, inflammatory, or neoplastic. Having a working knowledge of lesions within this region and conducting a thorough history and physical examination generally enables the clinician to facilitate an appropriate workup and establish a diagnosis. The differential diagnosis is broad, and expeditiously distinguishing benign from malignant masses is critical for instituting a timely multidisciplinary approach to the management of malignant lesions. Neoplasms of the head and neck account for approximately 5% of all childhood malignancies. A diagnosis of malignancy may represent a primary tumor or metastatic foci to cervical nodes. In this review, we discuss the general approach to evaluating suspicious masses and adenopathy in the head and neck region and summarize the most common malignant neoplasms of the head and neck with regard to their incidence, clinical presentation, diagnostic evaluation, staging, and management. Thyroid, parathyroid, and salivary gland tumors are discussed elsewhere in this issue of Seminars in Pediatric Surgery.
Neoplasms in young dogs after perinatal irradiation
Benjamin, S.A.; Lee, A.C.; Angleton, G.M.; Saunders, W.J.; Miller, G.K.; Williams, J.S.; Brewster, R.D.; Long, R.I.
For a study of the life-time effects of irradiation during development, 1,680 beagles were given single, whole-body exposures to /sup 60/Co gamma-radiation at one of three prenatal (preimplantation, embryonic, and fetal) or at one of three postnatal (neonatal, juvenile, and young adult) ages. Mean doses were 0, 0.16, or 0.83 Gy. For comparison with data on childhood cancer after prenatal irradiation, examination was made of tumors occurring in young dogs in this life-span experiment. Up to 4 years of age, 18 dogs had neoplasms diagnosed, 2 of these being in controls. Four dogs that were irradiated in the perinatal (late fetal or neonatal) period died of cancers prior to 2 years of age. This risk was of significant increase compared to the risks for other experimental groups and for the canine population in general. Overall, 71% (5 of 7) of all cancers and 56% (10 of 18) of all benign and malignant neoplasms seen in the first 4 years of life occurred in 29% (480 of 1680) of the dogs irradiated in the perinatal period. These data suggest an increased risk for neoplasia after perinatal irradiation in dogs.
Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects.
Acalovschi, Monica; Dumitrascu, Dan L.; Hagiu, Claudia
Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.
Pathology and genetics of pancreatic neoplasms with acinar differentiation.
Wood, Laura D; Klimstra, David S
Pancreatic neoplasms with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma, and carcinomas with mixed differentiation, are distinctive pancreatic neoplasms with a poor prognosis. These neoplasms are clinically, pathologically, and genetically unique when compared to other more common pancreatic neoplasms. Most occur in adults, although pancreatoblastomas usually affect children under 10 years old. All of these neoplasms exhibit characteristic histologic features including a solid or acinar growth pattern, dense neoplastic cellularity, uniform nuclei with prominent nucleoli, and granular eosinophilic cytoplasm. Exocrine enzymes are detectable by immunohistochemistry and, for carcinomas with mixed differentiation, neuroendocrine or ductal lineage markers are also expressed. The genetic alterations of this family of neoplasms largely differ from conventional ductal adenocarcinomas, with only rare mutations in TP53, KRAS, and p16, but no single gene or neoplastic pathway is consistently altered in acinar neoplasms. Instead, there is striking genomic instability, and a subset of cases has mutations in the APC/β-catenin pathway, mutations in SMAD4, RAF gene family fusions, or microsatellite instability. Therapeutically targetable mutations are often present. This review summarizes the clinical and pathologic features of acinar neoplasms and reviews the current molecular data on these uncommon tumors.
Incidental gallbladder cancer after cholecystectomy: 1990 to 2014
Dorobisz, Tadeusz; Dorobisz, Karolina; Chabowski, Mariusz; Pawłowski, Wiktor; Janczak, Dawid; Patrzałek, Dariusz; Janczak, Dariusz
Introduction Cancer of the gallbladder is a serious diagnostic and therapeutic problem. According to the literature, 30% of cases are not confirmed before surgery. Other cases are detected incidentally by histopathology. Clinical trials and meta-analyses show that incidental gallbladder cancer (iGBC) occurs in 0.19%–2.8% of patients after cholecystectomy. The aim of this study was to analyze the incidence and severity of iGBC in cholecystectomy procedures performed in the surgical department at the 4th Military Teaching Hospital in Wroclaw during the years 1990–2014. Patients and methods In the years 1990–2014, a total of 7,314 cholecystectomies were performed in the surgical department because of cholecystolithiasis: 6,145 were performed using the laparoscopic approach (84.02%), 867 were performed as open surgery (11.8%), and 302 cases required conversion (5.1%). In this group, 5,214 of the patients were females (71.3%) and 2,100 were males (28.7%), with an average age of 54.7 years. Results We found 64 iGBC cases which were confirmed by histopathology. This represented 0.87% of all cases. In this group, 50 patients were females (78.1%) and 14 were males (21.8%), with an average age of 67.1 years. Of this group, 40 patients underwent a classic cholecystectomy, while 24 underwent laparoscopic procedures, out of which 13 cases ultimately required traditional surgery. The histopathology showed 15 carcinomas that were classified as G1 (23.4%), 28 were G2 (43.75%), and 21 were G3 (32.8%). Conclusion iGBC detected after a cholecystectomy due to cholecystolithiasis is a rare disease. We found iGBC in 0.87% of cases, which is on a comparable scale to the world literature. In the case of cancer, we frequently found it necessary to convert to an open surgical procedure. This cancer is more common in females and in people over 60 years of age. PMID:27540304
Effect of Mutation Order on Myeloproliferative Neoplasms
Nangalia, Jyoti; Silber, Yvonne; Wedge, David C.; Grinfeld, Jacob; Baxter, E. Joanna; Massie, Charles E.; Papaemmanuil, Elli; Menon, Suraj; Godfrey, Anna L.; Dimitropoulou, Danai; Guglielmelli, Paola; Bellosillo, Beatriz; Besses, Carles; Döhner, Konstanze; Harrison, Claire N.; Vassiliou, George S.; Vannucchi, Alessandro; Campbell, Peter J.; Green, Anthony R.
BACKGROUND Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which mutations are acquired. METHODS We determined mutation order in patients with myeloproliferative neoplasms by genotyping hematopoietic colonies or by means of next-generation sequencing. Stem cells and progenitor cells were isolated to study the effect of mutation order on mature and immature hematopoietic cells. RESULTS The age at which a patient presented with a myeloproliferative neoplasm, acquisition of JAK2 V617F homozygosity, and the balance of immature progenitors were all influenced by mutation order. As compared with patients in whom the TET2 mutation was acquired first (hereafter referred to as "TET2-first patients"), patients in whom the Janus kinase 2 (JAK2) mutation was acquired first ("JAK2-first patients") had a greater likelihood of presenting with polycythemia vera than with essential thrombocythemia, an increased risk of thrombosis, and an increased sensitivity of JAK2-mutant progenitors to ruxolitinib in vitro. Mutation order influenced the proliferative response to JAK2 V617F and the capacity of double-mutant hematopoietic cells and progenitor cells to generate colony-forming cells. Moreover, the hematopoietic stem-and-progenitor-cell compartment was dominated by TET2 single-mutant cells in TET2-first patients but by JAK2–TET2 double-mutant cells in JAK2-first patients. Prior mutation of TET2 altered the transcriptional consequences of JAK2 V617F in a cell-intrinsic manner and prevented JAK2 V617F from up-regulating genes associated with proliferation. CONCLUSIONS The order in which JAK2 and TET2 mutations were acquired influenced clinical features, the response to targeted therapy, the biology of stem and progenitor cells, and clonal evolution in patients with myeloproliferative neoplasms. (Funded by Leukemia and Lymphoma Research
Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms.
Smedley, R C; Lamoureux, J; Sledge, D G; Kiupel, M
Definitive diagnosis of canine oral melanocytic neoplasms is often difficult because of variability in pigmentation and cellular pleomorphism. These neoplasms can resemble carcinomas, sarcomas, and round cell neoplasms, which differ in prognosis and treatment. A variety of immunohistochemical antibodies have been used for diagnosis of melanocytic neoplasms in humans and dogs; however, sensitivity and specificity of many markers have not been determined in amelanotic melanocytic neoplasms in dogs. The authors investigated a comprehensive panel of immunohistochemical markers in 49 canine oral amelanotic melanocytic neoplasms--namely, Melan-A, PNL2, HMB-45, microphthalmia transcription factor (MiTF), S-100, tyrosine hydroxylase, tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), and CD34. Ten well-differentiated cutaneous soft tissue spindle cell sarcomas were negative controls. Melan-A, PNL2, TRP-1, and TRP-2 were highly sensitive and 100% specific for the diagnosis of canine oral amelanotic melanocytic neoplasms. S-100 and MiTF showed high sensitivity but were less specific; that is, they also labeled a proportion of the soft tissue spindle cell sarcomas. HMB-45, tyrosinase, and tyrosine hydroxylase were 100% specific but had low sensitivities. CD34 did not label any of the melanocytic neoplasms but did label 80% of the soft tissue spindle cell sarcomas. A cost-effective and efficient immunodiagnostic cocktail containing antibodies against PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100% specificity and 93.9% sensitivity in identifying canine oral amelanotic melanocytic neoplasms. The spindloid variant was the variant with the lowest sensitivity to the cocktail. The likelihood of correctly diagnosing canine oral amelanotic melanocytic neoplasms was dramatically higher when biopsy samples contained ample overlying and adjacent epithelium.
Colonoscopy Atlas of Colon Polyps and Neoplasms.
Tang, Shou-Jiang; Sones, James Q
Optical colonoscopy is the gold standard for colon cancer screening and adenoma detection and is the only screening option that can potentially provide therapeutic interventions and adenoma removal during the same session. When other screening strategies generate positive results, currently colonoscopy is the next step for definitive diagnosis and potentially curative therapy. For gastrointestinal endoscopists, the ileocecum is the finishing line during colonoscopy, and it is identified by three endoscopic landmarks: terminal ileum, ileocecal valve, and the appendiceal orifice. Careful and systematic examination should be stressed during endoscopic training and practice. In this pictorial review, the authors demonstrate common colon polyps and neoplasms that can be found during colonoscopy. Our aim is to educate gastroenterologists, endoscopy staff other health care providers, and interested patients on certain colon pathologies and common endoscopic interventions.
Zosteriform cutaneous leiomyoma: a rare cutaneous neoplasm.
Cutaneous leiomyomas are firm, round to oval, skin-coloured to brownish papules and nodules that may present as a solitary, few discrete or multiple clustered lesions. Different uncommon patterns of multiple leiomyoma distribution have been noted as bilateral, symmetrical, linear, zosteriform, or dermatomal-like arrangement. One such rare presentation was seen in a 23-year-old patient who presented with zosteriform skin coloured, occasionally painful cutaneous lesions over left shoulder region. Histopathology confirmed the diagnosis of cutaneous leiomyoma. He was symptomatically managed with non-steroidal anti-inflammatory agents and topical capcicum cream. Case is reported here due to rare occurrence of this benign cutaneous neoplasm in an atypical pattern and on uncommon site.
Cholesteryl esters in human malignant neoplasms.
Tosi, M R; Bottura, G; Lucchi, P; Reggiani, A; Trinchero, A; Tugnoli, V
Cholesteryl esters (CholE) were detected in human malignant neoplasms by means of in vitro nuclear magnetic resonance spectroscopy. Spectroscopic analysis of the total lipid extracts obtained from cerebral tumors revealed appreciable amount of esterified cholesterol in high grade gliomas such as glioblastomas and anaplastic oligodendrogliomas, characterized by prominent neovascularity. The finding that no CholE were detected in the healthy brain and in low grade and benign tumors supports a possible correlation between this class of lipids and histological vascular proliferation. Compared with high grade gliomas, renal cell carcinomas show higher levels of CholE, absent in the healthy renal parenchyma and in benign oncocytomas. In nefro-carcinomas, cytoplasmic lipid inclusions and prominent vascularization contribute to the increased levels of CholE present mainly as oleate. CholE are discussed as potential biochemical markers of cancer and as a target for new therapeutic strategies.
Increased risk of lymphoid neoplasm in patients with myeloproliferative neoplasm: a study of 1,915 patients
Rumi, Elisa; Passamonti, Francesco; Elena, Chiara; Pietra, Daniela; Arcaini, Luca; Astori, Cesare; Zibellini, Silvia; Boveri, Emanuela; Pascutto, Cristiana; Lazzarino, Mario
Within a cohort of 1,915 consecutive patients with myeloproliferative neoplasm followed for a median time of 5.2 years (range 0–33.3), we investigated the occurrence of lymphoid neoplasm with the aim of defining this risk and to investigate the role of genetic predisposing factors. We identified 22 patients with myeloproliferative neoplasm who developed lymphoid neoplasm over their lifetime. We found that the risk of developing lymphoid neoplasm was 2.79-fold higher (95% CI, 1.80–4.33; P<0.001) than that of the general Italian population. A tag SNP surrogate for JAK2 GGCC haplotype was used to clarify a potential correlation between lymphoid-myeloid neoplasm occurrence and this genetic predisposing factor. As we did not find any difference in GGCC haplotype frequency between patients with both myeloid and lymphoid neoplasm and patients with myeloid neoplasm, JAK2 GGCC haplotype should not be considered a genetic predisposing factor. No difference in familial clustering was observed between the two groups. PMID:21109692
Incidence of colorectal neoplasms among male pilots
Moshkowitz, Menachem; Toledano, Ohad; Galazan, Lior; Hallak, Aharon; Arber, Nadir; Santo, Erwin
AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots. METHODS: Initial screening colonoscopy was performed on average-risk (no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center (ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC. RESULTS: There were 270 pilots (mean age 55.2 ± 7.4 years) and 1150 controls (mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls (P = 0.097, χ2 test). There were significantly more hyperplastic polyps among pilots (15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas (14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively (P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively (P = 0.93). CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population. PMID:25083084
The Effects of Ginger on Gallbladder Motility in Healthy Male Humans
Chuah, Seng-Kee; Tai, Wei-Chen; Changchien, Chi-Sin
Background/Aims Ginger has been used to treat a number of diseases including those affecting the digestive tract. This study was aimed to investigate the effects of ginger on gallbladder volume and gastrointestinal sensation in healthy male subjects. Methods Nineteen healthy male volunteers (age 21.3 ± 3.9 years, body mass index 21.6 ± 1.9 kg/m2) were studied on 2 occasions in a double blind randomized crossover design. After ingesting ginger (1,200 mg) or placebo capsules (starch), abdominal ultrasound was used to measure the gallbladder volume (calculated from gallbladder width, depth and diameter) and ejection fraction following a standard test meal. Gastrointestinal symptoms were also recorded at regular intervals by visual analogue scales. Results There were no differences in gallbladder volume or ejection fraction between ginger and placebo. Abdominal symptoms of bloating, fullness, nausea, discomfort and hunger was not different between the 2 occasions. Conclusions Ginger (1,200 mg) may not affect gallbladder ejection fraction and possible relevant abdominal symptoms in healthy male human subjects. PMID:22148111
Modern perspectives on factors predisposing to the development of gallbladder cancer
Pilgrim, Charles H C; Groeschl, Ryan T; Christians, Kathleen K; Gamblin, T Clark
Background Gallbladder cancer (GBC) is a rare malignancy, yet certain groups are at higher risk. Knowledge of predisposing factors may facilitate earlier diagnosis by enabling targeted investigations into otherwise non-specific presenting signs and symptoms. Detecting GBC in its initial stages offers patients their best chance of cure. Methods PubMed was searched for recent articles (2008–2012) on the topic of risk factors for GBC. Of 1490 initial entries, 32 manuscripts reporting on risk factors for GBC were included in this review. Results New molecular perspectives on cholesterol cycling, hormonal factors and bacterial infection provide fresh insights into the established risk factors of gallstones, female gender and geographic locality. The significance of polyps in predisposing to GBC is probably overstated given the known dysplasia–carcinoma and adenoma–carcinoma sequences active in this disease. Bacteria such as Salmonella species may contribute to regional variations in disease prevalence and might represent powerful targets of therapy to reduce incidences in high-risk areas. Traditional risk factors such as porcelain gallbladder, Mirizzi's syndrome and bile reflux remain important as predisposing factors. Conclusions Subcentimetre gallbladder polyps rarely become cancerous. Because gallbladder wall thickening is often the first sign of malignancy, all gallbladder imaging should be scrutinized carefully for this feature. PMID:23458506
Optical diagnosis of gallbladder cancers via two-photon excited fluorescence imaging of unstained histological sections.
Hong, Zhipeng; Chen, Youting; Chen, Jing; Chen, Hong; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin
Two-photon excited fluorescence (TPEF) microscopy, based on signal from cells, can provide detailed information on tissue architecture and cellular morphology in unstained histological sections to generate subcellular-resolution images from tissue directly. In this paper, we used TPEF microscopy to image microstructure of human normal gallbladder and three types of differentiated carcinomas in order to investigate the morphological changes of tissue structure, cell, cytoplasm, and nucleus without hematoxylin and eosin (H&E) staining. It displayed that TPEF microscopy can well image the stratified normal gallbladder tissue, including the mucosa, the muscularis, and the serosa. The typical cancer cell, characterized by cellular and nuclear pleomorphism, enlarged nuclei, and augmented nucleolus, can be identified in histological sections without H-E staining as well. The quantitative results showed that the areas of the nucleus and the nucleolus in three types of cancerous cells were all significantly greater than those in normal gallbladder columnar epithelial cells derived from TPEF microscopic images. The studies demonstrated that TPEF microscopy has the ability to characterize tissue structures and cell morphology of gallbladder cancers differentiated from a normal gallbladder in a manner similar to traditional histological analysis. As a novel tool, it has the potential for future retrospective studies of tumor staging and migration by utilizing histological section specimens without H-E staining.
Metachromatic leukodystrophy and its effects on the gallbladder: a case report.
Rodriguez-Waitkus, Paul M; Byrd, Robert; Hicks, John
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of arylsulfatase A enzyme. This deficiency leads to accumulation of sulfatides in the central nervous system and other organs, such as the gallbladder. Here the authors discuss a 9-year-old Middle Eastern patient with late-infantile-type MLD who presented with symptoms of cholecystitis. Radiographic studies revealed an enlarged gallbladder with a thickened wall and a pericholecystic fluid collection with peripheral calcifications. Gross examination of the gallbladder showed multiple small to medium-sized papillary projections involving the entire mucosal surface. Sections through the gallbladder wall revealed multilocular dilated mucin-producing cystic spaces. Microscopically, the mucosa showed numerous papillary projections with complex folds lined by mucin-producing cuboidal to tall columnar cells. The cystic spaces were composed of numerous markedly distended Rokitansky-Aschoff sinuses filled with mucin. Ultrastructurally, the epithelial cells and macrophages showed frequent secondary lysosomes containing closely packed lamellar amorphous to prismatic material with alternating leaflets and tubules, imparting a "herringbone" or "tuffstone" pattern. This case illustrates the features of gallbladder involvement in MLD and the potential role of ultrastructural examination in diagnosis of MLD.
Changes in guinea pig gallbladder smooth muscle Ca2+ homeostasis by acute acalculous cholecystitis.
Gomez-Pinilla, Pedro J; Morales, Sara; Camello-Almaraz, Cristina; Moreno, Rosario; Pozo, María J; Camello, Pedro J
Impaired smooth muscle contractility is a hallmark of acute acalculous cholecystitis. Although free cytosolic Ca2+ ([Ca2+]i) is a critical step in smooth muscle contraction, possible alterations in Ca2+ homeostasis by cholecystitis have not been elucidated. Our aim was to elucidate changes in the Ca2+ signaling pathways induced by this gallbladder dysfunction. [Ca2+]i was determined by epifluorescence microscopy in fura 2-loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. F-actin content was quantified by confocal microscopy. Ca2+ responses to the inositol trisphosphate (InsP3) mobilizing agonist CCK and to caffeine, an activator of the ryanodine receptors, were impaired in cholecystitic cells. This impairment was not the result of a decrease in the size of the releasable pool. Inflammation also inhibited Ca2+ influx through L-type Ca2+ channels and capacitative Ca2+ entry induced by depletion of intracellular Ca2+ pools. In addition, the pharmacological phenotype of these channels was altered in cholecystitic cells. Inflammation impaired contractility further than Ca2+ signal attenuation, which could be related to the decrease in F-actin that was detected in cholecystitic smooth muscle cells. These findings indicate that cholecystitis decreases both Ca2+ release and Ca2+ influx in gallbladder smooth muscle, but a loss in the sensitivity of the contractile machinery to Ca2+ may also be responsible for the impairment in gallbladder contractility.
Risk factors for gallbladder contractility after cholecystolithotomy in elderly high-risk surgical patients
Wang, Tao; Luo, Hao; Yan, Hong-tao; Zhang, Guo-hu; Liu, Wei-hui; Tang, Li-jun
Objective Cholecystolithiasis is a common disease in the elderly patient. The routine therapy is open or laparoscopic cholecystectomy. In the previous study, we designed a minimally invasive cholecystolithotomy based on percutaneous cholecystostomy combined with a choledochoscope (PCCLC) under local anesthesia. Methods To investigate the effect of PCCLC on the gallbladder contractility function, PCCLC and laparoscope combined with a choledochoscope were compared in this study. Results The preoperational age and American Society of Anesthesiologists (ASA) scores, as well as postoperational lithotrity rate and common biliary duct stone rate in the PCCLC group, were significantly higher than the choledochoscope group. However, the pre- and postoperational gallbladder ejection fraction was not significantly different. Univariable and multivariable logistic regression analyses indicated that the preoperational thickness of gallbladder wall (odds ratio [OR]: 0.540; 95% confidence interval [CI]: 0.317–0.920; P=0.023) and lithotrity (OR: 0.150; 95% CI: 0.023–0.965; P=0.046) were risk factors for postoperational gallbladder ejection fraction. The area under receiver operating characteristics curve was 0.714 (P=0.016; 95% CI: 0.553–0.854). Conclusion PCCLC strategy should be carried out cautiously. First, restricted by the diameter of the drainage tube, the PCCLC should be used only for small gallstones in high-risk surgical patients. Second, the usage of lithotrity should be strictly limited to avoid undermining the gallbladder contractility and increasing the risk of secondary common bile duct stones. PMID:28138229
Brush cells of rodent gallbladder and stomach epithelia express neurofilaments.
Luciano, Liliana; Groos, Stephanie; Reale, Enrico
It has been suggested that brush cells (BCs), a distinct type of cell occurring in various epithelia of the respiratory and gastrointestinal tracts, may function as receptor cells. The major characteristics of BCs are a prominent brush border and an unusually highly ordered arrangement of cytoskeletal elements (F-actin, microtubules, and intermediate filaments). In this study we aimed to characterize the nature of the intermediate filaments in BCs by light and electron microscopic immunostaining. Gallbladder and stomach specimens from mice and rats, respectively, were fixed in various solutions, embedded either in paraffin or epoxy resin, and processed for immunodetection. Commercially available, well-characterized antibodies against neurofilaments, peripherin, and cytokeratin peptide 18 were used. The polyclonal antiserum cocktail to neurofilaments was applied as a supplement in a double-labeling procedure with anti-actin and anti-cytokeratin 18 antibodies. The results demonstrate that the BCs of both organs express two types of intermediate filaments, i.e., neurofilaments and cytokeratin 18 filaments, and that these have a compartmentalized distribution in the cytoplasm. BCs do not express peripherin. The immunodetection of intermediate filaments distinctive for mature neurons in BCs supports their putative receptor function. The co-expression of neurofilaments and cytokeratins is shown for the first time in healthy tissues.
Concomitant Gastroparesis Negatively Impacts Children with Functional Gallbladder Disease
Chumpitazi, Bruno P.; Malowitz, Stanton M.; Moore, Warren; Gopalakrishna, G.S.; Shulman, Robert J.
Objectives The aim of this study was to determine if concomitant gastroparesis and biliary dyskinesia occur in children, and if so, to determine if concomitant gastroparesis affects clinical outcome in children with biliary dyskinesia. Methods: We conducted a retrospective chart review of children with biliary dyskinesia (ejection fraction <35% on cholescintigraphy, with no other metabolic, or structural cause) who completed a solid-phase gastric emptying scintigraphy scan within 12 months of the abnormal cholescintigraphy. Children were classified into one of four clinical outcome groups (excellent, good, fair, poor). Results Thirty-five children with a mean follow-up time of 23.1 ± 17.3 (SD) months were included. 20 (57%) children were identified as having concomitant gastroparesis with biliary dyskinesia. Children with concomitant gastroparesis were more likely to have a poor clinical outcome compared to those with biliary dyskinesia alone (P<0.005). In children undergoing cholecystectomy, those with concomitant gastroparesis were more likely to have a fair or poor clinical outcome compared to those with biliary dyskinesia alone (P<0.01). Factors predicting a more favorable clinical outcome were having biliary dyskinesia alone, and not having limitations in activity (e.g. school absences) at time of presentation. Conclusions Concomitant gastroparesis may occur in children with functional gallbladder disorders. Concomitant gastroparesis may negatively impact clinical outcome in children with biliary dyskinesia. PMID:22588599
Claudin-7-positive synchronous spontaneous intrahepatic cholangiocarcinoma, adenocarcinoma and adenomas of the gallbladder in a Bearded dragon (Pogona vitticeps).
Jakab, Csaba; Rusvai, Miklós; Szabó, Zoltán; Gálfi, Péter; Marosán, Miklós; Kulka, Janina; Gál, János
In this study, synchronous spontaneous, independent liver and gallbladder tumours were detected in a Bearded dragon (Pogona vitticeps). The multiple tumours consisted of intrahepatic cholangiocarcinoma as well as in situ adenocarcinoma and two adenomas of the gallbladder. The biliary epithelial cells and the cholangiocarcinoma showed membranous cross-immunoreactivity for claudin-7. The gallbladder epithelial cells, its adenoma and adenocarcinoma showed basolateral cross-reactivity for claudin-7. We think that the humanised anti-claudin-7 antibody is a good marker for the detection of different primary cholangiocellular and gallbladder tumours in Bearded dragons. The cholangiocytes, the cholangiocarcinoma, the endothelial cells of the liver and the epithelial cells and gallbladder tumours all showed claudin-5 cross-reactivity. The humanised anti-cytokeratin AE1-AE3 antibody showed cross-reactivity in the biliary epithelial cells, cholangiocarcinoma cells, epithelial cells and tumour cells of the gallbladder. It seems that this humanised antibody is a useful epithelial marker for the different neoplastic lesions of epithelial cells in reptiles. The humanised anti-α-smooth muscle actin (α-SMA) antibody showed intense cross-reactivity in the smooth muscle cells of the hepatic vessels and in the muscle layer of the gallbladder. The portal myofibroblasts, the endothelial cells of the sinusoids and the stromal cells of the cholangiocarcinoma and gallbladder tumours were positive for α-SMA. The antibovine anti-vimentin and humanised anti-Ki-67 antibodies did not show crossreactivity in the different samples from the Bearded dragon.
Topics in histopathology of sweat gland and sebaceous neoplasms.
Ansai, Shin-Ichi
This article reviews several topics regarding sweat gland and sebaceous neoplasms. First, the clinicopathological characteristics of poroid neoplasms are summarized. It was recently reported that one-fourth of poroid neoplasms are composite tumors and one-fourth are apocrine type lesions. Recent progress in the immunohistochemical diagnosis of sweat gland neoplasms is also reviewed. CD117 can help to distinguish sweat gland or sebaceous tumors from other non-Merkel cell epithelial tumors of the skin. For immunohistochemical differential diagnosis between sweat gland carcinoma (SGC) other than primary cutanesous apocrine carcinoma and skin metastasis of breast carcinoma (SMBC), a panel of antibodies may be useful, including p63 (SGC(+) , SMBC(-) ), CK5/6 (SGC(+) , SMBC(-) ), podoplanin (SGC(+) , SMBC(-) ) and mammaglobin (SGC(-) , SMBC(+) ). Comparison of antibodies used for immunohistochemical diagnosis of sebaceous carcinoma (SC) suggests that adipophilin has the highest sensitivity and specificity. Some authors have found that immunostaining for survivin, androgen receptor and ZEB2/SIP1 has prognostic value for ocular SC, but not extraocular SC. In situ SC is rare, especially extraocular SC, but there have been several recent reports that actinic keratosis and Bowen's disease are the source of invasive SC. Finally, based on recent reports, classification of sebaceous neoplasms into three categories is proposed, which are sebaceoma (a benign neoplasm with well-defined architecture and no atypia), borderline sebaceous neoplasm (low-grade SC; an intermediate tumor with well-defined architecture and nuclear atypia) and SC (a malignant tumor with invasive growth and evident nuclear atypia).
Undifferentiated carcinoma of the gallbladder with endothelial differentiation: A case report and literature review
Furuya, Yoshitaka; Hiroshima, Kenzo; Wakahara, Takashi; Akimoto, Harutoshi; Yanagie, Hironobu; Harigaya, Kenichi; Yasuhara, Hiroshi
Undifferentiated carcinoma of the gallbladder is a rare cancer type with a poor prognosis. The present study described a case of undifferentiated gallbladder carcinoma of the spindle- and giant-cell type, according to the 2010 World Health Organization classification. Hematoxylin and eosin staining revealed that the tumor consisted of dense interlacing bundles of spindle-shaped cells. No evidence of cartilaginous, osseous or rhabdomyosarcomatous differentiation was observed. Immunohistochemical staining revealed that spindle- and polygonal-shaped cells of the undifferentiated carcinoma were positive for cytokeratin AE1/3, vimentin and vascular endothelial growth factor. Furthermore, numerous spindle-shaped cells were positive for cluster of differentiation (CD)34 and CD31, and certain spindle-shaped cells were positive for Factor VIII. These results suggested classification of the present case as 'undifferentiated gallbladder carcinoma with endothelial differentiation'. PMID:28101355
A rare case of ascariasis in the gallbladder, choledochus and pancreatic duct.
Gönen, Korcan Aysun; Mete, Rafet
Due to the anatomical characteristics of the biliary tract, Ascaris lumbricoides rarely settles in the gallbladder, which makes biliary ascariasis a rare clinical condition. Ultrasonography plays a significant and practical role in the diagnosis and follow-up of suspected cases of biliary ascariasis. The 15-year-old case presented herein had been complaining of abdominal pain and dyspepsia for three months, and the clinical and laboratory findings for the patient indicated acute abdomen. Abdominal ultrasonography showed worms consistent with Ascaris inside a normal-sized gallbladder, dilated choledochus and the pancreatic duct. We started antiparasitic treatment in the patient, with cholangitis and pancreatitis diagnoses. Post-treatment follow-up ultrasonography showed a normal gallbladder, choledochus and pancreatic duct.
DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer
Gallbladder cancer is an infrequent neoplasia with noticeable geographical variations in its incidence around the world. In Chile, it is the main cause of death owing to cancer in women over 40 years old, with mortality rates up to 16.5 per 100,000 cases. The prognosis is poor with few therapeutic options; in advanced cases there is only a 10% survival at 5 years. Several studies mention the possible role of DNA methylation in gallbladder carcinogenesis. This epigenetic modification affects tumor suppressor genes involved in regulation pathways, cell cycle control, cell adhesion and extracellular matrix degradation, in a sequential and cumulative way. Determining DNA methylation patterns would allow them to be used as biomarkers for the early detection, diagnosis, prognosis and/or therapeutic selection in gallbladder cancer. PMID:22794276
Role of sincalide cholescintigraphy in the evaluation of patients with acalculus gallbladder disease
Pickleman, J.; Peiss, R.L.; Henkin, R.; Salo, B.; Nagel, P.
Thirty-six patients with biliary colic and normal oral cholecystograms, upper gastrointestinal tract roentgenograms, and results of gallbladder ultrasonography underwent sincalide-stimulated biliary excretion scanning. Nineteen of these patients subsequently underwent cholecystectomies. Gallbladder ejection fractions (EFs) ranged from 0% to 88% (mean, 38%) and nine of 19 patients had exact pain reproduction with sincalide. All patients except one (EF, 35%) were cured of their symptoms. However, five patients were also cured who had a normal EF (greater than 50%). Histologically, 11 gallbladders showed chronic cholecystitis and eight were normal. The authors conclude that the sincalide biliary excretion scan is a useful test to study this group of patients. In patients with a decreased EF, cholecystectomy can be recommended with a high probability of symptom relief. In patients with normal EFs, clinical judgment is required, as some of these patients (five of five in this series) may still benefit from operation.
Gallbladder dynamics induced by a fatty meal in normal subjects and patients with gallstones: concise communication.
Bobba, V R; Krishnamurthy, G T; Kingston, E; Turner, F E; Brown, P H; Langrell, K
A study was undertaken to establish the pattern of gallbladder emptying in normal subjects and in patients with gallstones, using a fatty meal as stimulus to release endogenous cholecystokinin. The time from meal ingestion to beginning of gallbladder emptying (latent period), the total duration of emptying (ejection period), degree of emptying (ejection fraction), and the rate of emptying (ejection fraction/ejection period) were measured noninvasively by a nongeometric scintigraphic technique. The mean latent period and ejection rate were similar in normal subjects and patients with gallstones, but the mean ejection period and ejection fraction were significantly reduced in the patients. This study suggests that for an identical stimulus, the gallbladder in cholelithiasis begins to empty at the normal time but empties for a shorter duration; the result is a reduction of ejection fraction but not of ejection rate.
Agenesis of the Gallbladder: Role of Clinical Suspicion and Magnetic Resonance to Avoid Unnecessary Surgery
Tagliaferri, Eugenio; Bergmann, Heinrich; Hammans, Sebastian; Shiraz, Aziz; Stüber, Eckhard; Seidlmayer, Christoph
Isolated agenesis of the gallbladder is usually a rare asymptomatic anatomical variation, with an estimated incidence of 10–65 per 100,000. Females are more commonly affected (ratio 3: 1), with the disease typically presenting in the second or third decade of their life. Despite an absent gallbladder, half of the patients present with symptoms similar to biliary colic, which is poorly understood. The rarity of this condition combined with its clinical and radiological features often lead to a wrong preoperative diagnosis so that many patients undergo unnecessary operative intervention. Herein, we present the case of a 56-year-old female with a typical biliary colic who was diagnosed to have gallbladder agenesis. Computed tomography and magnetic resonance cholangiopancreatography allowed correct treatment and prevented an unnecessary intervention. PMID:28203130
The Imaging and Pathological Features of Metastatic Leiomyosarcoma in the Gallbladder
Guo, Yi; Chen, Eleanor; Davidson, Darin J.; Pillarisetty, Venu G.; Jones, Robin L.
Uterine leiomyosarcoma is a rare and aggressive malignancy with poor overall prognosis. There have been few reports of metastatic leiomyosarcoma in the gallbladder. We report a case of a 41-year-old female who underwent total abdominal hysterectomy due to presumed uterine fibroids. The postoperative pathology revealed high-grade pleomorphic leiomyosarcoma, with involvement of the uterine serosal surface. She subsequently underwent exploratory laparotomy, followed by pelvic radiation and chemotherapy. Since initial management she has developed metastatic disease and has been under treatment and surveillance for 11 years. She has undergone multiple surgical procedures and numerous lines of systemic therapy for metastatic leiomyosarcoma, including cholecystectomy for a metastatic lesion in the gallbladder. There have been no previous reports of metastatic leiomyosarcoma in the gallbladder. Despite extensive metastatic disease this patient has had prolonged survival with multi-modality management. PMID:28191293
Gallbladder Volvulus: A Rare Emergent Cause of Acute Cholecystitis, if Untreated, Progresses to Necrosis and Perforation
Justin L, Regner Angela, Lomas
An 86 year-old woman with a past medical history significant for abdominal hernia and Alzheimer dementia presented to the Emergency Department with a 24 hour history of acute right upper quadrant pain associated with nausea and non-bilious emesis. Physical exam revealed right sided abdominal tenderness with associated mass. All laboratory values were within normal ranges. Both abdominal ultrasound and computed tomography of the abdomen/pelvis revealed a large distended gallbladder with wall thickening and gallstones. Based on presentation and radiologic findings, the emergency general surgery service was consulted for suspected acute cholecystitis. The patient was then admitted for intravenous antibiotics and scheduled for laparoscopic cholecystectomy the following day. Intra-operative findings revealed volvulus with acute necrosis of the entire gallbladder. The gallbladder had a long pedunculated cystic duct and artery that was detorsed before proceeding with resection. Postoperatively, the patient did well and was discharged a few days later tolerating a regular diet.
Solid and papillary epithelial neoplasm of the pancreas
Friedman, A.C.; Lichtenstein, J.E.; Fishman, E.K.; Oertel, J.E.; Dachman, A.H.; Siegelman, S.S.
Solid and papillary epithelial neoplasm of the pancreas is an uncommon low grade malignant tumor histologically distinct from the usual ductal adenocarcinoma and amenable to cure by surgical excision. It tends to occur in black women in their second or third decade of life and has often been misclassified as nonfunctional islet cell tumor or as cystadenoma or cystadenocarcinoma. Twelve cases were reviewed. Sonography and CT of solid and pipillary epithelial neoplasms depict a well-demarcated mass that can be solid, mixed cystic and solid, or largely cystic. The radiologic appearance is dependent on the maintenance of the integrity of the neoplasm versus the extent of retrogressive changes that have occurred.
Intraductal Papillary Mucinous Neoplasm of Pancreas
Machado, Norman Oneil; al Qadhi, Hani; al Wahibi, Khalifa
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are neoplasms that are characterized by ductal dilation, intraductal papillary growth, and thick mucus secretion. This relatively recently defined pathology is evolving in terms of its etiopathogenesis, clinical features, diagnosis, management, and treatment guidelines. A PubMed database search was performed. All the relevant abstracts in English language were reviewed and the articles in which cases of IPMN could be identified were further scrutinized. Information of IPMN was derived, and duplication of information in several articles and those with areas of persisting uncertainties were excluded. The recent consensus guidelines were examined. The reported incidence of malignancy varies from 57% to 92% in the main duct-IPMN (MD-IPMN) and from 6% to 46% in the branch duct-IPMN (BD-IPMN). The features of high-risk malignant lesions that raise concern include obstructive jaundice in a patient with a cystic lesion in the pancreatic head, the findings on radiological imaging of a mass lesion of >30 mm, enhanced solid component, and the main pancreatic duct (MPD) of size ≥10 mm; while duct size 5-9 mm and cyst size <3 mm are considered as "worrisome features." Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are primary investigations in diagnosing and following up on these patients. The role of pancreatoscopy and the analysis of aspirated cystic fluid for cytology and DNA analysis is still to be established. In general, resection is recommended for most MD-IPMN, mixed variant, and symptomatic BD-IPMN. The 5-year survival of patients after surgical resection for noninvasive IPMN is reported to be at 77-100%, while for those with invasive carcinoma, it is significantly lower at 27-60%. The follow-up of these patients could vary from 6 months to 1 year and would depend on the risk stratification for invasive malignancy and the pathology of the resected specimen. The understanding of
Intraductal oncocytic papillary neoplasms of the pancreas.
Adsay, N V; Adair, C F; Heffess, C S; Klimstra, D S
We describe the clinical and pathologic features of 11 intraductal oncocytic papillary neoplasms of the pancreas, a hitherto unrecognized tumor. The patients were six men and five women, and most of the tumors were in the head (head: body/tail = 8:3). The mean patient age was 62 (range, 39-78), and the average tumor size was 6 cm. Grossly the tumors exhibited mucin-filled cysts containing nodular papillary projections. Dilated ducts communicating with the main tumor were sometimes noted. Microscopically the cystic structures appeared to represent dilated ducts containing intraductal tumor. The tumors were characterized by variably complex, arborizing papillary structures. The papillae had thin, delicate fibrovascular cores with focal myxoid changes and were lined by stratified oncocytic cells. Goblet cells and intra-epithelial mucin-containing lumina were present, the latter resulting in a characteristic cribriform pattern. The exuberance of the epithelial proliferation varied from case to case and between different regions within individual tumors; solid sheets of cells were often identified. Although the degree of cytologic atypia was not generally severe, the complexity of the architecture justified a designation of intraductal oncocytic papillary carcinoma in 10 of the 11 cases. In nine cases the tumor was entirely intraductal; one case exhibited focal microinvasion and another showed widespread invasive carcinoma, the invasive elements appearing cytologically similar to the intraductal papillary components. The oncocytic cells stained positively with phosphotungstic acid hematoxylin and Novelli stains. Immunohistochemically, all cases stained positively for B72.3, and five cases showed focal, weak luminal membrane staining for carcinoembryonic antigen. Ultrastructurally many of the cells were packed with mitochondria, and mucin was also identified. Seven patients were alive and free of tumor from 1 month to 3 years (average, 1 year) after resection. Two
Gallbladder edema in type 1 diabetic patient due to delayed-type insulin allergy.
Kawasaki, Fumiko; Kamei, Shinji; Tatsumi, Fuminori; Hamamoto, Sumiko; Shimoda, Masashi; Tawaramoto, Kazuhito; Shigeto, Makoto; Kanda, Yukiko; Hashiramoto, Mitsuru; Matsuki, Michihiro; Kaku, Kohei
A 29-year-old woman was diagnosed as having type 1 diabetes mellitus and received insulin aspart and NPH insulin (NovolinN). On day 22, she had leg edema and right abdominal pain. The serum hepatobiliary enzyme levels were markedly elevated. Computed tomography revealed gallbladder edema. After an injection of human regular insulin and NPH insulin (HumacartN), the elevated liver enzyme levels were no longer observed. Challenge testing demonstrated that protamine was the cause of her allergy. Furthermore, tests revealed increased VEGF levels. This is an extremely rare case with a delayed-type protamine allergy caused by NovolinN resulting in gallbladder edema.
Idiopathic perforation of acalculous gallbladder after insertion of a transpapillary pancreatic stent
Katagiri, Tomoko; Irisawa, Atsushi; Wakabayashi, Hiroto; Tsunoda, Takuya; Tomoda, Hiroyuki; Saito, Ryo; Kinuta, Shunji
Background and study aims: Endoscopic retrograde pancreatocholangiography (ERCP) is associated with many types of adverse events (AEs) but idiopathic perforation of the gallbladder (IPGB) is very rare. Pancreatobiliary reflux is one of the factors involved with occurrence of IPGB 1. Here we present a case of acalculous gallbladder perforation as an AE following the insertion of an indwelling endoscopic nasal pancreatic drainage (ENPD) tube (a pancreatic stent) to obtain pancreatic fluid. In this case, acute pancreatobiliary reflux might have been caused by the insertion of the ENPD-tube. PMID:27540570
[Ultrasound-guided cutaneous intercostal branches nerves block: A good analgesic alternative for gallbladder open surgery].
Fernández Martín, M T; López Álvarez, S; Mozo Herrera, G; Platero Burgos, J J
Laparoscopic cholecystectomy has become the standard treatment for gallbladder diseases. However, there are still some patients for whom conversion to open surgery is required. This surgery can produce significant post-operative pain. Opioids drugs have traditionally been used to treat this pain, but side effects have led to seeking alternatives (plexus, nerve or fascia blocks or wound). The cases are presented of 4 patients subjected to ultrasound-guided intercostal branches blocks in the mid-axillary line from T6 to T12 with levobupivacaine as an analgesic alternative in open surgery of gallbladder, with satisfactory results.
The Empty Gallbladder Syndrome—Results of Operation for Noncalculous Biliary Disorders
Ferraris, Ltc Victor A.
Based on results of long-term follow-up and pathophysiologic considerations in 38 consecutive patients, it was possible to speculate on the frequencies of the various causes of the empty gallbladder syndrome. In approximate percentages, these are as follows: bile stasis causing chronic acalculous cholecystitis, 47%; physiologic dysfunction of the gallbladder, 24%; psychogenic illness, 16%; sphincter of Oddi dysfunction, 13%; ulcerative colitis, 3%. Because as many as 30% to 35% of these patients will not benefit from cholecystectomy, I feel that it should be undertaken with caution in cases of this syndrome. PMID:3716403
Pancreas divisum: correlation between anatomical abnormalities and bile precipitation in the gallbladder in seven patients
Pancreas divisum is a genetic defect associated with recurrent acute pancreatitis due to insufficient drainage of the accessory pancreatic duct. Seven young patients diagnosed with pancreatic divisum and thickening of the gallbladder bile as shown on magnetic resonance cholangio-pancreatography without pancreatic ductal changes underwent laparoscopic cholecystectomy. During the mean follow-up of 32 months no episode of pancreatitis was reported. There is an association between PD and higher concentration of bile in the gallbladder. Cholecystectomy can be considered curative in patients with PD in the absence of indications for major surgery. PMID:27938531
Cholecystokinin enhanced hepatobiliary scanning with ejection fraction calculation as an indicator of disease of the gallbladder
Zech, E.R.; Simmons, L.B.; Kendrick, R.R.; Soballe, P.W.; Olcese, J.A.; Goff, W.B. II; Lawrence, D.P.; DeWeese, R.A. )
Chronic acalculous cholecystitis represents 5 to 20 per cent of electively treated diseases of the gallbladder. A 70 per cent success rate in relieving these patients of chronic pain was reported when surgical treatment was recommended based on symptoms alone. The cholecystokinin ejection fraction, which is a quantitative measure of emptying of the gallbladder, was 95 per cent accurate in predicting which patients would be relieved of symptoms by surgical treatment. In this study, we report our consecutive experience during a 20 month period with 83 patients.
Rare entity: Ectopic liver tissue in the wall of the gallbladder - A case report.
Arslan, Yusuf; Altintoprak, Fatih; Serin, Kursat R; Kivilcim, Taner; Yalkin, Omer; Ozkan, Orhan V; Celebi, Fehmi
Ectopic liver tissue (ELT) is a rare condition, which is usually not diagnosed preoperatively, but coincidentally during abdominal surgery. While the location of ELT can vary, it is usually localized on the gallbladder wall or in close proximity. ELT is associated with various complications, a major complication being extrahepatic hepatocellular carcinoma. A 59-year-old female underwent elective surgery for chronic cholecystitis with stones. During laparoscopic exploration, a 2-cm-diameter ELT was detected in the anterior gallbladder wall and a laparoscopic cholecystectomy was performed. The case is presented due to the rare nature of ELT and as a reminder of ELT-related complications.
Gas-containing gallstones as a cause of the "effervescent gallbladder" sign and pneumobilia.
Niederhauser, Blake D; Atwell, Thomas D; MacCarty, Robert L; Bender, Claire E
The "effervescent gallbladder" sign, the sonographic finding of tiny echogenic foci rising from the dependent portion of the gallbladder, reminiscent of bubbles rising in a glass of champagne, has been reported previously as a finding of emphysematous cholecystitis. We report two additional cases of this unusual finding in an asymptomatic patient and in a patient with acute, gangrenous cholecystitis, confirmed in both cases by CT, to be secondary to the release of gas from gallstones. These two cases cast doubt on the sonographic sign as a pathognomonic finding of emphysematous cholecystitis.
Incidental gallbladder cancer diagnosed during and after laparoscopic cholecystectomy.
Shimizu, Tetsuya; Arima, Yasuo; Yokomuro, Shigeki; Yoshida, Hiroshi; Mamada, Yasuhiro; Nomura, Tsutomu; Taniai, Nobuhiko; Aimoto, Takayuki; Nakamura, Yoshiharu; Mizuguchi, Yoshiaki; Kawahigashi, Yutaka; Uchida, Eiji; Akimaru, Koho; Tajiri, Takashi
With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC), the number of cases of incidental gallbladder carcinoma (GBC) has increased; however, management of incidental GBC is a difficult issue in the absence of established guidelines. The present study aims to evaluate the treatment of patients with incidental GBC diagnosed with LC. We performed a 14-year review of 10 patients with GBC discovered with LC. From April 1991 through March 2004, we performed LC for 1,195 patients at Nippon Medical School Main Hospital. Of these patients, 10 (0.83%) were found to have GBC. Seven patients were women and 3 were men, with a mean age of 61.4 years. Four patients had mucosal tumors (pT1a), 5 had subserosal tumors (pT2), and 1 had a serosal lesion (pT3). Eight of the 10 patients underwent radical surgery. Two patients with pT1a tumors underwent no additional surgery. All 4 patients with pT1a tumors are alive without recurrence. One patient with a pT2 tumor with metastases to the liver and pericholedochal lymph nodes found with additional resection died of recurrence of metastasis to the liver and lung 70 months after LC. One patient with a pT2 tumor died of primary lung cancer 35 months after LC. The remaining 3 patients with pT2 tumors are alive without recurrence 51 to 128 months after surgery. One patient with a pT3 tumor is alive with no recurrence for 9 months. For stage Tis or T1a tumors, LC is sufficient. Patients with T1b tumors should undergo liver-bed resection and lymphadenectomy, and patients with >pT2 tumors should undergo systematic liver resection with lymphadenectomy. Even when incidental GBC diagnosed with LC is advanced, adequate additional surgery may improve the prognosis.
Liver Resection in Children with Hepatic Neoplasms
Randolph, Judson G.; Altman, R. Peter; Arensman, Robert M.; Matlak, Michael E.; Leikin, Sanford L.
In the past ten years, 28 patients with primary tumors of the liver have been treated. There were 11 benign tumors, including four hamartomas, three patients with focal nodular hyperplasia, and two each with congenital cysts and hemangioma. Hamartomas and masses of focal nodular hyperplasia should be excised when possible, but both are benign lesions; therefore life threatening excisions at the porta hepatis should be avoided. Cysts are often resectable, but when occupying all lobes of the liver, they can be successfully managed by marsupialization into the free peritoneal cavity. If resectable, hemangiomas should be removed; when occupying most of the liver as they often do, patients may be subject to platelet trapping or to cardiac failure. In some instances these lesions have been controlled by steroids, radiation therapy or hepatic artery ligation. Of 17 malignant tumors seen, 12 proved to be hepatoblastomas. Nine of the 12 patients underwent liver resection, of whom four are cured, (33%). There were three children with hepatocellular carcinomas and two with embryonal rhabdomyosarcoma. One child from each of these groups is cured by surgical excision. At present the only known cures in children with primary malignant liver neoplasms have been achieved by operative removal. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4. PMID:206216
Guidelines for the management of myeloproliferative neoplasms
Choi, Chul Won; Bang, Soo-Mee; Jang, Seongsoo; Jung, Chul Won; Kim, Hee-Jin; Kim, Ho Young; Kim, Soo-Jeong; Kim, Yeo-Kyeoung; Park, Jinny; Won, Jong-Ho
Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are collectively known as 'Philadelphia-negative classical myeloproliferative neoplasms (MPNs).' The discovery of new genetic aberrations such as Janus kinase 2 (JAK2) have enhanced our understanding of the pathophysiology of MPNs. Currently, the JAK2 mutation is not only a standard criterion for diagnosis but is also a new target for drug development. The JAK1/2 inhibitor, ruxolitinib, was the first JAK inhibitor approved for patients with intermediate- to high-risk myelofibrosis and its effects in improving symptoms and survival benefits were demonstrated by randomized controlled trials. In 2011, the Korean Society of Hematology MPN Working Party devised diagnostic and therapeutic guidelines for Korean MPN patients. Subsequently, other genetic mutations have been discovered and many kinds of new drugs are now under clinical investigation. In view of recent developments, we have revised the guidelines for the diagnosis and management of MPN based on published evidence and the experiences of the expert panel. Here we describe the epidemiology, new genetic mutations, and novel therapeutic options as well as diagnostic criteria and standard treatment strategies for MPN patients in Korea. PMID:26552452
The Hematopoietic Niche in Myeloproliferative Neoplasms
Schmitt-Graeff, Annette H.; Nitschke, Roland; Zeiser, Robert
Specialized microanatomical areas of the bone marrow provide the signals that are mandatory for the maintenance and regulation of hematopoietic stem cells (HSCs) and progenitor cells. A complex microenvironment adjacent to the marrow vasculature (vascular niche) and close to the endosteum (endosteal niche) harbors multiple cell types including mesenchymal stromal cells and their derivatives such as CAR cells expressing high levels of chemokines C-X-C motif ligand 12 and early osteoblastic lineage cells, endothelial cells, and megakaryocytes. The characterization of the cellular and molecular networks operating in the HSC niche has opened new perspectives for the understanding of the bidirectional cross-talk between HSCs and stromal cell populations in normal and malignant conditions. A structural and functional remodeling of the niche may contribute to the development of myeloproliferative neoplasms (MPN). Malignant HSCs may alter the function and survival of MSCs that do not belong to the neoplastic clone. For example, a regression of nestin+ MSCs by apoptosis has been attributed to neuroglial damage in MPN. Nonneoplastic MSCs in turn can promote aggressiveness and drug resistance of malignant cells. In the future, strategies to counteract the pathological interaction between the niche and neoplastic HSCs may offer additional treatment strategies for MPN patients. PMID:26696752
CALR mutation characterization in myeloproliferative neoplasms
Bilbao-Sieyro, Cristina; Florido, Yanira; Gómez-Casares, María Teresa
Identification of somatic frameshift mutations in exon 9 of the calreticulin gene (CALR) in myeloproliferative neoplasms (MPNs) in December of 2013 has been a remarkable finding. It has provided a new molecular diagnostic marker, particularly in essential thrombocythemia (ET) and primary myelofibrosis (PMF), where is the second most common altered gene after JAK2V617F. There are two main types of CALR mutants, type 1 and type 2, and there is evidence about their distinct clinical/prognostic implications, for instances, it is believed that favorable outcome might be restricted to type-1 in PMF. By using reasoned approaches, very recent publications have supported classifying the alternative mutants in type-1-like or type-2-like. If further studies confirm these results, new considerations may be taken into account in the molecular diagnosis of MPNs. This implies that precise mutation characterization must be performed and caution should be taken in screening technique selection. In this Editorial we summarize the current information regarding all this issues. PMID:27384487
Eponyms in cardiothoracic radiology: Part I. Neoplasms.
Mohammed, Tan-Lucien H; Saettele, Megan R; Saettele, Timothy; Patel, Vikas; Kanne, Jeffrey P
Eponyms serve the purpose of honoring individuals who have made important observations and discoveries. As with other fields of medicine, eponyms are frequently encountered in radiology, particularly in chest radiology. However, inappropriate use of an eponym may lead to potentially dangerous miscommunication. Moreover, an eponym may honor the incorrect person or a person who falls into disrepute. Despite their limitations, eponyms are still widespread in medical literature. Furthermore, in some circumstances, more than one individual may have contributed to the description or discovery of a particular anatomical structure or disease, whereas in others, an eponym may have been incorrectly applied initially and propagated for years in medical literature. Nevertheless, radiologic eponyms are a means of honoring those who have made lasting contributions to the field of radiology, and familiarity with these eponyms is critical for proper reporting and accurate communication. In addition, the acquisition of some historical knowledge about those whose names are associated with various structures or pathologic conditions conveys a sense of humanity in the field of medicine. In this article, the first of a multipart series, the authors discuss a number of chest radiology eponyms as they relate to neoplasms, including relevant clinical and imaging features, as well biographic information of the respective eponym׳s namesake.
Calreticulin Exon 9 Mutations in Myeloproliferative Neoplasms
Kim, Yu-Kyung
Background Calreticulin (CALR) mutations were recently discovered in patients with myeloproliferative neoplasms (MPNs). We studied the frequency and type of CALR mutations and their hematological characteristics. Methods A total of 168 MPN patients (36 polycythemia vera [PV], 114 essential thrombocythemia [ET], and 18 primary myelofibrosis [PMF] cases) were included in the study. CALR mutation was analyzed by the direct sequencing method. Results CALR mutations were detected in 21.9% of ET and 16.7% of PMF patients, which accounted for 58.5% and 33.3% of ET and PMF patients without Janus kinase 2 (JAK2) or myeloproliferative leukemia virus oncogenes (MPL) mutations, respectively. A total of five types of mutation were detected, among which, L367fs*46 (53.6%) and K385fs*47 (35.7%) were found to be the most common. ET patients with CALR mutation had lower leukocyte counts and ages compared with JAK2-mutated ET patients. Conclusion Genotyping for CALR could be a useful diagnostic tool for JAK2-or MPL-negative ET or PMF patients. CALR mutation may be a distinct disease group, with different hematological characteristics than that of JAK2-positive patients. PMID:25553276
Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)
... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...
General Information about Plasma Cell Neoplasms (Including Multiple Myeloma)
... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...
Primary malignant neoplasms associated with chronic lymphocytic leukaemia.
Lishner, M.; Prokocimer, M.; Ron, E.; Shaklai, M.
The relationship between chronic lymphocytic leukaemia (CLL) and primary malignant neoplasms was evaluated using data from the Hematology Division in Beilinson Medical Center and the Israel Cancer Registry. The study population consisted of 81 patients diagnosed between 1962 and 1984. A total of 16 patients were found to have 21 malignant neoplasms in addition to their CLL. Excluding patients with nonmelanoma skin tumours, a 1.7 increased risk (statistically not significant) for developing second malignant neoplasms in CLL patients was detected. The only tumour which occurred significantly more than expected subsequent to CLL diagnosis was brain cancer. The coexistence of multiple cancers in the same patient was diagnosed in four of the patients. The results of this study further support the hypothesis that patients with CLL are prone to develop second neoplasms. PMID:3684832
Radiation myelopathy of cervical spinal cord simulating intramedullary neoplasm
Fogelholm, R.; Haltia, M.; Andersson, L. C.
Radiation myelopathy is a well-known complication of irradiation therapy of neoplasms in the vicinity of the spinal cord. Most earlier authors have stressed the association of a normal myelogram and normal CSF protein level with this condition. One case of radiation myelopathy with a myelogram simulating intramedullary neoplasm and with extremely high CSF protein concentration is presented. Six months after myelography necropsy revealed severe atrophy of the previously thickened lower cervical spinal cord. The pathogenetic mechanisms are discussed. Images PMID:4443812
Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm
Corrales, J. J.; Robles-Lázaro, C.; Sánchez-Marcos, A. I.; González-Sánchez, M. C.; Antúnez-Plaza, P.; Miralles, J. M.
Adrenocortical oncocytic neoplasms (oncocytomas) are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol) and androgens (androstenedione and DHEAS), a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing's syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline) according to the Lin-Weiss-Bisceglia criteria. PMID:27413559
Intraductal tubular neoplasms of the pancreas: an overview.
Chelliah, Adeline; Kalimuthu, Sangeetha; Chetty, Runjan
Intraductal lesions of the pancreas are an uncommon but increasingly recognized group of entities mainly because of advances in imaging technology. In the past, precise categorization and understanding of true pancreatic intraduct neoplasms were hampered not only by their relative rarity but also because of the plethora of terminology and criteria used in nomenclature and diagnosis. Although significant progress has been made in the characterization of some of these lesions, as exemplified by intraductal papillary mucinous neoplasms, understanding of the rare intraductal tubular adenoma (ITA) and intraduct tubular carcinoma (ITC) continues to evolve. By definition, these are a group of intraductal, radiologically detectable neoplasms that can progress to or be associated with invasive adenocarcinoma and, as such, are precursor lesions to pancreatic ductal adenocarcinoma. Their often shared clinical and radiological features make precise histological diagnosis essential for appropriate management and optimal outcome. We provide an overview of these neoplasms and highlight recent developments in the understanding of ITA and ITC which have led to ITA being considered a variant of gastric-type intraductal papillary mucinous neoplasms and ITC being encompassed within the intraductal tubulopapillary neoplasm category. We also emphasize the distinguishing histological features to aid diagnosis of these rare lesions.
CT characteristics of primary retroperitoneal neoplasms in children.
Xu, Yufeng; Wang, Jichen; Peng, Yun; Zeng, Jinjin
Primary retroperitoneal neoplasms are uncommon in children. Retroperitoneal neoplasms are either mesodermal, neurogenic, germ cell ectodermal or lymphatic in origin. In general, primary retroperitoneal neoplasms in children have different spectrum and prevalence compared to those in adults. Neuroblastoma, rhabdomyosarcoma, benign teratoma and lymphoma are the common retroperitoneal neoplasms. In this review, the clinical and CT futures of common retroperitoneal neoplasms in children are described. Coarse, amorphous, and mottled calcification are very common in neuroblastoma. Paraganglioma tends to show marked and early enhancement and may present with clinical symptoms associated with the excess catecholamine. Sarcomas are often very large and have heterogeneous appearance. Imaging cannot be reliably used to identify the type of retroperitoneal sarcomas due to overlapped radiographic features. In children, lipoblastoma is the most common lipomatous tumor in the retroperitoneum. The percentage of visible fat in tumor varies depending on the cellular composition of the lesion. The CT characteristics of teratoma are quite variable, which may be cystic, solid, on a combination of both. Typically teratoma appears as a large complex mass containing fluid, fat, fat-fluid level, and calcifications. Lymphoma is often homogeneous on both enhanced and unenhanced CT scans. Necrosis and calcification are rare on CT. In conclusion, making a final histological diagnosis of retroperitoneal tumor base on CT features is not often possible; however, CT can help to develop a differential diagnosis and determine the size and extent of the retroperitoneal neoplasms.
Identification of suitable reference genes for investigating gene expression in human gallbladder carcinoma using reverse transcription quantitative polymerase chain reaction.
Yu, Shan; Yang, Qiwei; Yang, Jing Hui; Du, Zhenwu; Zhang, Guizhen
Reverse transcription quantitative polymerase chain reaction (RT‑qPCR) has become a frequently used strategy in gene expression studies. The relative quantification method is an important and commonly used method for the evaluation of RT‑qPCR data. The key aim of this method is to identify an applicable internal reference gene, however, there are currently no suitable reference genes for gene analysis in gallbladder carcinoma. In the present study, screening was performed using 12 common reference genes, which were selected in order to provide an experimental basis for the investigation of gene expression in gallbladder carcinoma. A total of 16 tissue samples of gallbladder carcinoma and their matched normal gallbladder tissues were used. The gene expression stability and applicability of the 12 reference gene candidates were determined using the geNorm, NormFinder and BestKeeper software programs. Following comparison of the results of the three software programs, HPRT1 was identified as the most stably expressed reference gene. In the normal gallbladder group, the relative stably expressed reference gene was PPIA and in the entire sample group, the relatively stably expressed reference gene was PPIA. The present study also demonstrated that the combination of the three reference genes was the most appropriate. The recommended combinations were PPIA + PUM1 + ACTB for the total sample group, GAPDH + PBGD + ALAS1 for the gallbladder carcinoma group and PPIA + PUM1 + TBP for the paired normal gallbladder group.
Rokitansky-Aschoff sinuses of the gallbladder are associated with black pigment gallstone formation: a scanning electron microscopy study.
Cariati, Andrea; Cetta, Francesco
Rokitansky-Aschoff sinuses are the result of hyperplasia and herniation of epithelial cells through the fibromuscular layer of the gallbladder wall and are usually referred to as adenomyomatosis. The role of this study is to demonstrate that Rokitansky-Aschoff sinuses of the gallbladder are a risk factor for the formation of black pigment gallstones. A total of 179 removed gallbladders, were hystologically examined. Sixty-four of the 179 consecutive cholecystomized patients had typical adenomyomatosis. Thirty-eight of the 64 patients with adenomyomatosis had black pigment gallstones, alone (n=22) or in association with single (n=12) or multiple (n=4) cholesterol gallstones in the same gallbladder. Twelve of these patients did not have the typical risk factors for black stones (hemolysis, cirrhoses, gastrectomy, etc). Gallstones were examined by infrared spectroscopy and X-ray diffractometry. In addition, in a subset of 14 patients, the gallstones and the gallbladder wall were examined by scanning electron microscopy. At least in the initial phases of formation, Rokitansky-Aschoff sinuses were found close to small intraparietal vessels and sometimes they contained black pigment microstones. After the fourth to fifth decades of life, black gallstones can be found in the Rokitansky-Aschoff sinuses and in the main gallbladder lumen. Black pigment gallstones can form in Rokitansky-Aschoff sinuses of the gallbladder in absence of the typical risk factors for bilirubin suprasaturation of bile.
Incidental non-benign gallbladder histopathology after cholecystectomy in an United Kingdom population: Need for routine histological analysis?
Patel, Krashna; Dajani, Khaled; Iype, Satheesh; Chatzizacharias, Nikolaos A; Vickramarajah, Saranya; Singh, Prateush; Davies, Susan; Brais, Rebecca; Liau, Siong S; Harper, Simon; Jah, Asif; Praseedom, Raaj K; Huguet, Emmanuel L
AIM To analyse the range of histopathology detected in the largest published United Kingdom series of cholecystectomy specimens and to evaluate the rational for selective histopathological analysis. METHODS Incidental gallbladder malignancy is rare in the United Kingdom with recent literature supporting selective histological assessment of gallbladders after routine cholecystectomy. All cholecystectomy gallbladder specimens examined by the histopathology department at our hospital during a five year period between March 2008 and March 2013 were retrospectively analysed. Further data was collected on all specimens demonstrating carcinoma, dysplasia and polypoid growths. RESULTS The study included 4027 patients. The majority (97%) of specimens exhibited gallstone or cholecystitis related disease. Polyps were demonstrated in 44 (1.09%), the majority of which were cholesterol based (41/44). Dysplasia, ranging from low to multifocal high-grade was demonstrated in 55 (1.37%). Incidental primary gallbladder adenocarcinoma was detected in 6 specimens (0.15%, 5 female and 1 male), and a single gallbladder revealed carcinoma in situ (0.02%). This large single centre study demonstrated a full range of gallbladder disease from cholecystectomy specimens, including more than 1% neoplastic histology and two cases of macroscopically occult gallbladder malignancies. CONCLUSION Routine histological evaluation of all elective and emergency cholecystectomies is justified in a United Kingdom population as selective analysis has potential to miss potentially curable life threatening pathology. PMID:27830040
Overview of the clinical problem: facts and current issues of mucinous cystic neoplasms of the pancreas.
Jeurnink, S M; Vleggaar, F P; Siersema, P D
Pancreatic cystic lesions are uncommon and consist of pseudocysts, congenital cysts and cystic neoplasms including mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms. Mucinous cystic neoplasms are large septated cysts without connection to the ductal system, characterised by the presence of thick-walled ovarian-type stroma and mucin. They occur predominantly in women and often are malignant. Therefore, surgical resection is recommended. Intraductal papillary mucinous neoplasms are neoplasms with tall, columnar, mucin-containing epithelium involving the main pancreatic ducts or major side branches. Intraductal papillary mucinous neoplasms occur in men and women in their 60s and 70s and may differentiate into malignant neoplasms. Therefore, surgical resection is mandatory. Serous cystic neoplasms appear as multiple cysts lined with cubic flat epithelium containing glycogen-rich cells with clear cytoplasm. They mainly occur in women in their 50s and are generally benign. Therefore, a conservative approach is recommended. As both mucinous cystic neoplasm and intraductal papillary mucinous neoplasms have a high malignant potential, it is important to differentiate between the various pancreatic cystic lesions. Several imaging techniques and tumour markers have been evaluated. Nonetheless, definitive guidelines to differentiate between serous cystic neoplasms, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are still poorly defined. A number of management issues regarding these neoplasms are still under debate, for example which imaging technique to use, differentiation between malignant or benign lesions and the preferred treatment modality for each pancreatic cystic neoplasm. Further research may lead to a definitive guideline for the diagnosis and treatment of mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms.
Intrahepatic Biliary Intraductal Oncocytic Papillary Neoplasm/Carcinoma: First Reported Case in Australia and Literature Review.
Chu, Christopher; Felbel, William; Chu, Francis
Biliary (hepatic and extrahepatic) intraductal papillary mucinous neoplasms and intraductal oncocytic papillary neoplasms/carcinoma are rare neoplasms. Classification of biliary intraductal papillary tumors can be confusing and reports in radiology literature are extremely limited. We describe the first reported case of biliary intraductal oncocytic papillary neoplasms/carcinoma in the liver in Australia. The intraductal nature of such neoplasms can be identified on magnetic resonance imaging and magnetic resonance cholangiopancreatography.
Gallbladder visualization during technetium-99m-labeled red cell scintigraphy for gastrointestinal bleeding
Brill, D.R.
Localization of radionuclide activity in the gallbladder was seen on delayed views following injection of 99mTc-labeled red blood cells for gastrointestinal bleeding in five patients. The mechanism for this unusual finding probably relates to labeling of heme, the biochemical precursor of bilirubin. All patients had had prior transfusions. All but one had severe renal impairment, probably an important predisposing factor.
Congenital duplex gallbladder and biliary mucocele associated with partial hepatic cholestasis and cholelithiasis in a cat
Woods, Katharine S.; Brisson, Brigitte A.; Defarges, Alice M.N.; Oblak, Michelle L.
A 6-year-old neutered male domestic shorthair cat was presented for acute onset of vomiting. Exploratory laparotomy identified a duplex gallbladder and left cholecystectomy was performed. Histopathology confirmed biliary mucocele and hepatic cholestasis. While rare, biliary mucoceles should be considered as a differential diagnosis for feline extrahepatic bile duct obstruction. PMID:22942442
Concomitant gastroparesis occurs in functional gallbladder disease and may negatively impact clinical outcome
Technology Transfer Automated Retrieval System (TEKTRAN)
Functional gallbladder disease, commonly known as Biliary Dyskinesia (BD), is an increasingly recognized cause of chronic abdominal pain and dyspepsia in adults and children. Similar symptoms may occur in those with Gastroparesis (GP). The potential role and impact of concomitant GP in those with BD...
Laparoscopic removal of a gallbladder remnant in a patient with severe biliary pancreatitis
Cawich, Shamir O; Mohammed, Fawwaz; Spence, Richard; Naraynsingh, Vijay
Many surgeons opt to perform subtotal cholecystectomy to limit duct injuries in difficult cases. In these cases, however, there is a risk for the gallbladder remnant to become diseased. In these cases, a completion cholecystectomy is necessary. Although technically challenging, the laparoscopic approach to completion cholecystectomy is feasible and safe, when performed by surgeons with advanced laparoscopic experience. PMID:27656198
Orai1 forms a signal complex with SK3 channel in gallbladder smooth muscle.
Song, Kai; Zhong, Xing-Guo; Xia, Xian-Ming; Huang, Jun-Hao; Fan, Yi-Fei; Yuan, Ren-Xiang; Xue, Nai-Rui; Du, Juan; Han, Wen-Xiu; Xu, A-Man; Shen, Bing
Orai1 is one of the key components of store-operated Ca(2+) entry (SOCE) involved in diverse physiological functions. Orai1 may associate with other proteins to form a signaling complex. In the present study, we investigated the interaction between Orai1 and small conductance Ca(2+)-activated potassium channel 3 (SK3). With the use of RNA interference technique, we found that the SOCE and its associated membrane hyperpolarization were reduced while Orai1 was knocked down by a specific Orai1 siRNA in guinea pig gallbladder smooth muscle. However, with the use of isometric tension measurements, our results revealed that agonist-induced muscle contractility was significantly enhanced after Orai1 protein was knocked down or the tissue was treated by SK3 inhibitor apamin, but not affected by larger conductance Ca(2+)-activated potassium channel inhibitor iberiotoxin or intermediate conductance Ca(2+)-activated potassium channel inhibitor TRAM-34. In addition, in the presence of apamin, Orai1 siRNA had no additional effect on agonist-induced contraction. In coimmunoprecipitation experiment, SK3 and Orai1 pulled down each other. These data suggest that, Orai1 physically associated with SK3 to form a signaling complex in gallbladder smooth muscle. Ca(2+) entry via Orai1 activates SK3, resulting in membrane hyperpolarization in gallbladder smooth muscle. This hyperpolarizing effect of Orai1-SK3 coupling could serve to prevent excessive contraction of gallbladder smooth muscle in response to contractile agonists.
[Unusual laparoscopic surgical cases: cholelithiasis in situs inversus totalis, and gallbladder agenesis].
Antal, András; Kovács, Zoltán; Szász, Krisztina
Organ anomalies and organ system transposition may cause diagnostic and therapeutic difficulties. We report a patient with situs inversus totalis and symptomatic cholelithiasis successfully treated via laparoscopic cholecystectomy. We present a laparoscopic and MR cholangiographic pictures of our patient with gallbladder agenesis.
Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: a possible stem cell tumor?
Paniz Mondolfi, Alberto E; Slova, Denisa; Fan, Wen; Attiyeh, Fadi F; Afthinos, John; Reidy, Jason; Pang, Yinghua; Theise, Neil D
A 48 year-old African American woman presented to her physician complaining of a rapidly evolving epigastric and right upper quadrant abdominal pain. A PET-CT of the abdomen and pelvis demonstrated hypermetabolic, polypoid masses within the gallbladder and several tumors in the left lobe of the liver for which she underwent diagnostic laparoscopy. The gallbladder revealed a 3.5 × 3.3 × 2.4 tan-brown exophytic mass located at the fundus and growing into the lumen with multiple contiguous papillary projections arising from the mucosal surface. A concurrent large cell neuroendocrine carcinoma and papillary adenocarcinoma of the gallbladder was revealed histologically. There was shared reactivity to antibodies directed against the distinct antigens for each morphological component with transitional tumor cells (of both histological components) located at the areas where the two tumor types merged, revealing common immunoreactivity for carcinoembryonic antigen, cancer antigen 19-9, keratin 19, c-kit (cluster of differentiation protein 117 (CD117)) and epithelial cell adhesion molecule. Ultrastructurally, individual cells were demonstrated to have overlapping features of neuroendocrine and glandular differentiation. The aforementioned histological, ultrastructural and immunohistochemical profile is strongly suggestive of a biphenotypic stem/progenitor cell tumor of the gallbladder.
[The characteristics of the development of gallbladder and biliary tract pathology under the influence of vibration].
Preobrazhenskiĭ, V N; Merkulov, V M; Vasil'ev, A Iu; Ermakova, T I; Borisov, B P
The examination of 86 helicopter pilots has shown that their exposure to vibration leads to biliary and gallbladder damage which aggravates with longer service. As indicated by spectroscopy and gas-liquid chromatography, vibration affects colloid-osmotic properties of bile: molecules grow in size, bile acids retention becomes longer.
Carcinoma in situ in a 7 mm gallbladder polyp: Time to change current practice?
Kasle, David; Rahnemai-Azar, Amir A; Bibi, Shahida; Gaduputi, Vinaya; Gilchrist, Brian F; Farkas, Daniel T
Detection of polypoid lesions of the gallbladder is increasing in conjunction with better imaging modalities. Accepted management of these lesions depends on their size and symptomatology. Polyps that are symptomatic and/or greater than 10 mm are generally removed, while smaller, asymptomatic polyps simply monitored. Here, a case of carcinoma-in-situ is presented in a 7 mm gallbladder polyp. A 25-year-old woman, who had undergone a routine cholecystectomy, was found to have an incidental 7 mm polyp containing carcinoma in situ. She had few to no risk factors to alert to her condition. There are few reported cases of cancer transformation in gallbladder polyps smaller than 10 mm reported in the literature. The overwhelming consensus, barring significant risk factors for cancer being present, is that such lesions should be monitored until they become symptomatic or develop signs suspicious for malignancy. In our patient's case this could have led to the possibility of missing a neoplastic lesion, which could then have gone on to develop invasive cancer. As gallbladder carcinoma is an aggressive cancer, this may have led to a tragic outcome.
Is routine ultrasound examination of the gallbladder justified in critical care patients?
Myrianthefs, Pavlos; Evodia, Efimia; Vlachou, Ioanna; Petrocheilou, Glykeria; Gavala, Alexandra; Pappa, Maria; Baltopoulos, George; Karakitsos, Dimitrios
Objective. We evaluated whether routine ultrasound examination may illustrate gallbladder abnormalities, including acute acalculous cholecystitis (AAC) in the intensive care unit (ICU). Patients and Methods. Ultrasound monitoring of the GB was performed by two blinded radiologists in mechanically ventilated patients irrespective of clinical and laboratory findings. We evaluated major (gallbladder wall thickening and edema, sonographic Murphy's sign, pericholecystic fluid) and minor (gallbladder distention and sludge) ultrasound criteria. Measurements and Results. We included 53 patients (42 males; mean age 57.6 ± 2.8 years; APACHE II score 21.3 ± 0.9; mean ICU stay 35.9 ± 4.8 days). Twenty-five patients (47.2%) exhibited at least one abnormal imaging finding, while only six out of them had hepatic dysfunction. No correlation existed between liver biochemistry and ultrasound results in the total population. Three male patients (5.7%), on the grounds of unexplained sepsis, were diagnosed with AAC as incited by ultrasound, and surgical intervention was lifesaving. Patients who exhibited ≥2 ultrasound findings (30.2%) were managed successfully under the guidance of evolving ultrasound, clinical, and laboratory findings. Conclusions. Ultrasound gallbladder monitoring guided lifesaving surgical treatment in 3 cases of AAC; however, its routine application is questionable and still entails high levels of clinical suspicion.
Occurrence of pancreatic, biliary tract, and gallbladder cancers in Alaska Native people, 1973–2007
Alberts, Steven R.; Kelly, Janet J.; Ashokkumar, Ramkumar; Lanier, Anne P.
Objectives To describe the occurrence of pancreatic, biliary tract, and gallbladder cancers within the Alaska Native (AN) population. Study design Population-based analysis utilizing a tumor registry and comparative population data. Methods Pancreaticobiliary cancers rates for AN people during 1973–2007 were determined from the Surveillance, Epidemiology, and End Results (SEER) AN Tumor Registry. Cancer incidence rates were age-adjusted to the World Standard Million and compared over 2 time periods with US white and black rates. Results During 1973–2007, 213 AN people developed pancreatic cancer, 73 gallbladder cancer and 61 biliary tract cancer. Pancreatic cancer occurs at similar rates in AN men and women, but data for 1993–2007 indicate that the rates among AN men may be increasing. The incidence rate in AN women (9.5/100,000) was statistically higher than in US white women (5.8/100,000). The incidence for biliary tract cancer in AN men and gallbladder cancer in AN men and women is statistically higher than that for US whites and blacks. Conclusions Pancreaticobiliary cancers, particularly biliary tract and gallbladder cancers, in both AN men and women and pancreatic cancer in women occur at an increased rate in AN people. Risk factors relating to the elevated rate are discussed. Certain factors are potentially modifiable, such as the use of tobacco and obesity. PMID:22456038
Mismatch repair genes in renal cortical neoplasms.
Baiyee, Daniel; Banner, Barbara
Mutation of human mutL homolog 1 (MLH-1) and human mutS homolog 2 (MSH-2) has been linked with the pathogenesis of colorectal carcinoma in hereditary nonpolyposis colorectal cancer syndrome and other carcinomas. Mutations of these genes in renal cell carcinomas were recently described. The aim of this study was to examine the expression of MLH-1 and MSH-2 in renal cortical neoplasms of various histological types by immunohistochemistry. Thirty-eight (n = 38) resected renal tumors were obtained from the surgical pathology files of the UMass Memorial Healthcare, including clear cell carcinomas (CLEARs, n = 20), papillary carcinomas (PAPs, n = 8), chromophobe carcinomas (CHRs, n = 4), and oncocytomas (ONCs, n = 6). Positive immunostaining for MLH-1 and MSH-2 was graded by the number of positive tumor cell nuclei, as follows: 0, negative; 1, up to one third of positive nuclei; 2, one to two thirds positive; and 3, greater than two thirds positive. Loss of MLH-1 or MSH-2 was defined as a tumor with grade 0 or 1, compared with the normal tubules. Normal tubules and intercalated ducts contained cells positive for MLH-1 and MSH-2 in all cases. For both antibodies, positive staining in tumors ranged from grade 1 to 3 in the CLEAR and PAP but was only grade 2 to 3 in the CHR and ONC. Loss of MLH-1 and/or MSH-2 occurred in malignant tumors but not in ONC. Loss of MLH-1 was present in 8 (40%) of 20 CLEARs and 4 (50%) of 8 PAPs, compared with loss of MSH-2 in 4 (20%) of 20 CLEARs and 1 (25%) of 4 CHRs. Our results suggest that loss of mismatch repair genes is involved in the malignant transformation in some renal carcinomas, particularly those derived from the proximal tubules.
Targeting glutamine metabolism in myeloproliferative neoplasms
Zhan, Huichun; Ciano, Kristen; Dong, Katherine; Zucker, Stanley
JAK2V617F mutation can be detected in the majority of myeloproliferative neoplasm (MPN) patients. The JAK2 inhibitor Ruxolitinib is the first FDA-approved treatment for MPNs. However, its use is limited by various dose related toxicities. Here, we studied the metabolic state and glutamine metabolism of BaF3-hEPOR-JAK2V617F and BaF3-hEPOR-JAK2WT cells. We found that the JAK2V617F-mutant cells were associated with increased oxygen consumption rate and extracellular acidification rate than the JAK2WT cells and there was an increased glutamine metabolism in JAK2V617F-mutant cells compared to wild-type cells. Glutaminase (GLS), the key enzyme in gluta-mine metabolism, was upregulated in the JAK2V617F-mutant BaF3 cells compared to the JAK2WT BaF3 cells. In MPN patient peripheral blood CD34+ cells, GLS expression was increased in JAK2V617F-mutant progenitor cells compared to JAK2 wild-type progenitor cells from the same patients and GLS levels were increased at the time of disease progression compared to at earlier time points. Moreover, GLS inhibitor increased the growth inhibitory effect of Ruxolitinib in both JAK2V617F-mutant cell lines and peripheral blood CD34+ cells from MPN patients. Therefore, GLS inhibitor should be further explored to enhance the therapeutic effectiveness of JAK2 inhibitor and allow the administration of lower doses of the drug to avoid its toxicity. PMID:26227854
Genetic–pathologic characterization of myeloproliferative neoplasms
Kim, Yonggoo; Park, Joonhong; Jo, Irene; Lee, Gun Dong; Kim, Jiyeon; Kwon, Ahlm; Choi, Hayoung; Jang, Woori; Chae, Hyojin; Han, Kyungja; Eom, Ki-Seong; Cho, Byung-Sik; Lee, Sung-Eun; Yang, Jinyoung; Shin, Seung-Hwan; Kim, Hyunjung; Ko, Yoon Ho; Park, Haeil; Jin, Jong Youl; Lee, Seungok; Jekarl, Dong Wook; Yahng, Seung-Ah; Kim, Myungshin
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade ⩾2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic–pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome. PMID:27444979
Calreticulin (CALR) mutation in myeloproliferative neoplasms (MPNs)
Luo, Wenyi
As a heterogeneous group of disease, myeloproliferative neoplasms (MPNs) have confused hematologists and hematopathologists with their protean clinical presentations and myriads of morphologies. A thought of classifying MPNs based on molecular alterations has gained popularity because there is increasing evidence that molecular or chromosomal alterations have a better correlation with clinical presentation, response to therapies, and prognosis than conventional morphological classification. This type of efforts has been facilitated by the advancement of molecular technologies. A significant number of gene mutations have been identified in MPNs with JAK2 and MPL being the major ones. However, a significant gap is present in that many cases of MPNs do not harbor any of these mutations. This gap is recently filled by the discovery of Calreticulin (CALR) mutation in MPNs without JAK2 or MPL mutation and since then, the clinical and molecular correlation in MPNs has become a hot research topic. There seems to be a fairly consistent correlation between CALR mutation and certain hematological parameters such as a high platelet count and a better prognosis in MPNs with CALR mutation. However, controversies are present regarding the risks of thrombosis, interactions of CALR with other gene mutation, the role of CALR in the pathogenesis, and the optimal treatment strategies. In addition, there are many questions remain to be answered, which all boiled down to the molecular mechanisms by which CALR causes or contributes to MPNs. Here, we summarized current published literatures on CALR mutations in MPNs with an emphasis on the clinical-molecular correlation. We also discussed the controversies and questions remain to be answered. PMID:27358884
Emerging treatments for classical myeloproliferative neoplasms.
Vannucchi, Alessandro M; Harrison, Claire N
There has been a major revolution in the management of patients with myeloproliferative neoplasms (MPN), and in particular those with myelofibrosis and extensive splenomegaly and symptomatic burden, after the introduction of the JAK1 and JAK2 inhibitor ruxolitinib. The drug also has been approved as second-line therapy for polycythemia vera (PV). However, the therapeutic armamentarium for MPN is still largely inadequate for coping with patients' major unmet needs, which include normalization of life span (myelofibrosis and some patients with PV), reduction of cardiovascular complications (mainly PV and essential thrombocythemia), prevention of hematological progression, and improved quality of life (all MPN). In fact, none of the available drugs has shown clear evidence of disease-modifying activity, even if some patients treated with interferon and ruxolitinib showed reduction of mutated allele burden, and ruxolitinib might extend survival of patients with higher-risk myelofibrosis. Raised awareness of the molecular abnormalities and cellular pathways involved in the pathogenesis of MPN is facilitating the development of clinical trials with novel target drugs, either alone or in combination with ruxolitinib. Although for most of these molecules a convincing preclinical rationale was provided, the results of early phase 1 and 2 clinical trials have been quite disappointing to date, and toxicities sometimes have been limiting. In this review, we critically illustrate the current landscape of novel therapies that are under evaluation for patients with MPN on the basis of current guidelines, patient risk stratification criteria, and previous experience, looking ahead to the chance of a cure for these disorders.
Myeloproliferative neoplasms: Current molecular biology and genetics.
Saeidi, Kolsoum
Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by increased production of mature blood cells. Philadelphia chromosome-negative MPNs (Ph-MPNs) consist of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A number of stem cell derived mutations have been identified in the past 10 years. These findings showed that JAK2V617F, as a diagnostic marker involving JAK2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs. Somatic mutations in an endoplasmic reticulum chaperone, named calreticulin (CALR), is the second most common mutation in patients with ET and PMF after JAK2 V617F mutation. Discovery of CALR mutations led to the increased molecular diagnostic of ET and PMF up to 90%. It has been shown that JAK2V617F is not the unique event in disease pathogenesis. Some other genes' location such as TET oncogene family member 2 (TET2), additional sex combs-like 1 (ASXL1), casitas B-lineage lymphoma proto-oncogene (CBL), isocitrate dehydrogenase 1/2 (IDH1/IDH2), IKAROS family zinc finger 1 (IKZF1), DNA methyltransferase 3A (DNMT3A), suppressor of cytokine signaling (SOCS), enhancer of zeste homolog 2 (EZH2), tumor protein p53 (TP53), runt-related transcription factor 1 (RUNX1) and high mobility group AT-hook 2 (HMGA2) have also identified to be involved in MPNs phenotypes. Here, current molecular biology and genetic mechanisms involved in MNPs with a focus on the aforementioned factors is presented.
Asbestos fibres detected by scanning electron microscopy in the gallbladder of patients with malignant pleural mesothelioma (MPM).
Grosso, F; Croce, A; Trincheri, N F; Mariani, N; Libener, R; Degiovanni, D; Rinaudo, C
Gallbladders from patients affected by both malignant pleural mesothelioma (MPM) and important gallbladder disorders were analyzed to verify the presence of asbestos fibres. Histological thin sections were analyzed by optical microscope and variable pressure scanning electron microscopy coupled with energy dispersive spectroscopy, allowing morphological and chemical characterization of each inorganic phase observed. Fibres of chrysotile and crocidolite, minerals regulated as asbestos, were identified. By immunohistochemical analysis, connective tissue was recognized as the incorporation site. These findings confirm that asbestos fibres can reach the gallbladders of patients with MPM, for whom the development of respiratory diseases confirms asbestos exposure.
Intrahepatic perforation of the gallbladder causing liver abscesses: case studies and literature review of a rare complication
Hussain, T; Adams, M; Ahmed, M; Arshad, N; Solkar, M
A spontaneous (non-traumatic) gallbladder perforation with gallstone disease is not common. Concomitant development of a liver abscess is a very rare complication observed in such cases. A few cases of intrahepatic gallbladder perforations with chronic liver abscesses have been described. However, a patient series summarising classical and atypical presentations, relevant imaging studies, and the role of surgical and non-surgical options are lacking. We report a short case series on this rare complication of intrahepatic gallbladder perforations and share our experience of management of this condition. PMID:27055407
Cystoisospora belli Infection of the Gallbladder in Immunocompetent Patients: A Clinicopathologic Review of 18 Cases.
Lai, Keith K; Goyne, Hannah E; Hernandez-Gonzalo, David; Miller, Kennon A; Tuohy, Marion; Procop, Gary W; Lamps, Laura W; Patil, Deepa T
Cystoisospora belli, previously known as Isospora belli, is an obligate intracellular coccidian parasite that is most often associated with gastrointestinal disease in immunocompromised patients. In this study, we detail the clinicopathologic features of 18 cases of Cystoisospora infection affecting the gallbladder in immunocompetent individuals and compare them with a control group. Each case was reviewed for cholecystitis (none, acute, chronic), epithelial disarray, presence of intraepithelial lymphocytes (none, rare [≤5 per 20 epithelial cells], present [>5 per 20 epithelial cells]), architectural distortion, intramucosal eosinophilia, and mural thickening/serositis. The mean age of patients with Cystoisospora infection was 33 years and the male to female ratio 1:4.3. Cholecystectomy was performed for biliary dyskinesia (n=7), abdominal pain (n=7), suspected cholelithiasis (n=5), and cholecystitis (n=3). In 2 cases, Cystoisospora was found in donor gallbladders resected at the time of liver transplantation. Each case was characterized by eosinophilic, oval or banana-shaped intraepithelial parasites within perinuclear parasitophorous vacuoles. Most cases showed epithelial disarray and minimal intraepithelial lymphocytosis. Of the 11 cases with an average follow-up of 15 months, none had evidence of disease related to Cystoisospora infection within the biliary tract or elsewhere in the gastrointestinal tract. We present the largest series of gallbladder cystoisosporiasis in immunocompetent patients to date. Cystoisospora infection is underrecognized in the gallbladders of immunocompetent patients, in part due to the subtle findings in routine cholecystectomy specimens. On the basis of the clinical follow-up, gallbladder cystoisosporiasis in immunocompetent individuals appears to be a self-limited infection.
Developmental changes in Ca2+ homeostasis and contractility in gallbladder smooth muscle.
Camello-Almaraz, Cristina; Macias, Beatriz; Gomez-Pinilla, Pedro J; Alcon, Soledad; Martin-Cano, Francisco E; Baba, Akemishi; Matsuda, Toshio; Camello, Pedro J; Pozo, María J
Relatively little is known about the contribution of Ca(2+)-dependent and -independent mechanisms in the contractility of neonatal gastrointestinal smooth muscle. We therefore studied Ca(2+) homeostasis and Ca(2+) sensitization mechanisms in 10-day-old and adult guinea pig gallbladder smooth muscle to elucidate developmental changes in these processes. Gallbladder contractility was evaluated by isometrical tension recordings from strips, intracellular Ca(2+) concentration was estimated by epifluorescence microscopy of fura-2-loaded isolated cells, and protein expression and phosphorylation were assessed by Western blot analysis. The neonatal gallbladder contracted significantly less to CCK than adult tissue, but this correlated with an increased Ca(2+) mobilization, suggesting immaturity of Ca(2+) sensitization mechanisms. The enhanced Ca(2+) release in the newborn gallbladder was the result of the increase in the size of the releasable Ca(2+) pool. Moreover, in neonatal smooth muscle cells, neither the plasma membrane Ca(2+) pump nor the Na(+)/Ca(2+) exchanger collaborate in the extrusion of Ca(2+). In contrast, in these cells, there is an increase in phospholamban phosphorylation, which could drive to an overactivity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase pump. The reduced Ca(2+) sensitivity in neonatal tissues was demonstrated by the lack of effect to Y-27362, an inhibitor of Rho kinase (ROCK), and GF-109203X, an inhibitor of PKC, on agonist-induced contraction. In addition, the neonatal gallbladder showed lower levels of RhoA, ROCK, PKC, and two effectors [C-kinase-dependent inhibitor of 17 kDa (CPI-17) and myosin phosphatase targetting 1 (MYPT1)] as well as an absence of CPI-17 and MYPT1 phosphorylation in response to agonists. In conclusion, our results indicate that the main mechanisms involved in smooth muscle contractility are under developmental regulation.
Body mass index, abdominal fatness and the risk of gallbladder disease.
Aune, Dagfinn; Norat, Teresa; Vatten, Lars J
Epidemiological studies have indicated a positive association between adiposity and gallbladder disease risk, however, the shape of the dose-response relationship and differences between overall and abdominal adiposity remains to be clarified. We conducted a systematic review and dose-response meta-analysis of cohort studies of body mass index (BMI), waist circumference and waist-to-hip ratio and risk of gallbladder disease. PubMed and Embase databases were searched up to January 9th 2015. Summary relative risks were calculated using a random effects model. Seventeen prospective studies of BMI and gallbladder disease risk with 55,670 cases among 1,921,103 participants were included. The summary relative risk (RR) for a 5 unit increment in BMI was 1.63 (95 % CI 1.49-1.78, I(2) = 98 %). There was evidence of a nonlinear association overall and among women, p(nonlinearity) < 0.0001, but not among men, p(nonlinearity) = 0.99, with a slight flattening of the curve at very high BMI levels (BMI 40-45), however, the risk of gallbladder disease increased almost twofold even within the "normal" BMI range. The summary RR for a 10 cm increase in waist circumference was 1.46 (95 % CI 1.24-1.72, I(2) = 98 %, n = 5) and for a 0.1 unit increment in waist-to-hip ratio was 1.44 (95 % CI 1.26-1.64, I(2) = 92 %, n = 4). Associations were attenuated, but still significant, when BMI and abdominal adiposity measures were mutually adjusted. Our results confirm a positive association between both general and abdominal fatness and the risk of gallbladder disease. There is an almost twofold increase in the risk even within the "normal" BMI range, suggesting that even moderate increases in BMI may increase risk.
Diabetes, gallbladder disease, obesity, and hypertension among Hispanics in New Mexico.
Samet, J M; Coultas, D B; Howard, C A; Skipper, B J; Hanis, C L
Because Hispanics in the Southwest are genetically admixed with American Indians, the hypothesis has been advanced that the excess occurrence of diabetes mellitus, obesity, and gallbladder disease in this ethnic group may be genetic in origin and results from genes derived from American Indians. This report describes the prevalence of these diseases in 1,175 adult Hispanic participants in a survey of a New Mexico community conducted in 1984-1985. At nearly all ages, the majority of subjects had a body mass index of 25 kg/m2 or greater, and a substantial proportion exceeded 30 kg/m2. The prevalence of obesity was much greater in these Hispanics than is shown in nationwide data for US whites. Diabetes mellitus was also reported more often by Hispanic subjects in this survey than by US whites nationwide. A report of gallbladder trouble or of gallbladder removal was common in both males and females; the prevalence of gallbladder removal was as high in this population as in Mexican Americans previously studied in Starr County, Texas. In spite of the high prevalence of obesity, hypertension was less frequent among the New Mexico Hispanics than is shown in nationwide data for US whites. These findings complement those of previous surveys in Texas, which have shown a notably high proportion of adults to be obese, to have non-insulin-dependent diabetes mellitus, and to have gallbladder disease. The similar epidemiology of these diseases in the Hispanics of New Mexico and the Mexican Americans of Texas supports the hypothesis that American Indian admixture underlies the development of these conditions in Hispanics throughout the Southwest.
Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2
Baxter, E.J.; Nice, F.L.; Gundem, G.; Wedge, D.C.; Avezov, E.; Li, J.; Kollmann, K.; Kent, D.G.; Aziz, A.; Godfrey, A.L.; Hinton, J.; Martincorena, I.; Van Loo, P.; Jones, A.V.; Guglielmelli, P.; Tarpey, P.; Harding, H.P.; Fitzpatrick, J.D.; Goudie, C.T.; Ortmann, C.A.; Loughran, S.J.; Raine, K.; Jones, D.R.; Butler, A.P.; Teague, J.W.; O'Meara, S.; McLaren, S.; Bianchi, M.; Silber, Y.; Dimitropoulou, D.; Bloxham, D.; Mudie, L.; Maddison, M.; Robinson, B.; Keohane, C.; Maclean, C.; Hill, K.; Orchard, K.; Tauro, S.; Du, M.-Q.; Greaves, M.; Bowen, D.; Huntly, B.J.P.; Harrison, C.N.; Cross, N.C.P.; Ron, D.; Vannucchi, A.M.; Papaemmanuil, E.; Campbell, P.J.; Green, A.R.
BACKGROUND Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with
Rous, Peyton; Kidd, John G.
The "warts" which tar elicits on rabbit skin (papillomas, carcinomatoids, frill horns) are true tumors, benign growths expressive of slight yet irreversible deviations of epidermal cells from the normal. The neoplastic condition gives the cells a superiority over their neighbors when both are submitted to the same encouraging influences, and then they proliferate into tumors. Their state entails such disabilities, though, that they are unable to maintain themselves under ordinary circumstances, and consequently growths composed of them disappear when no longer aided. Often the neoplastic cells resume the normal aspect and habit of life long before the tumor mass is gone; and they may persist as part of an apparently normal epidermis, retaining their neoplastic potentialities for months after all signs of the growth have disappeared. In these instances it can be made to appear again, sometimes repeatedly, by non-carcinogenic stimulation of the skin (wound healing, turpentining). There is reason however to suppose that in the end the tumor cells, unless helped, die or are cast off. It is plain that the neoplastic state does not necessarily connote independence of behavior or success in tumor formation. On the contrary it may render cells unable to survive or endow them with powers which they can exert only under favoring conditions. This is the case with the cells composing the tar warts of rabbits. In the lack of such conditions the cells of these growths do not manifest themselves but remain in a subthreshold neoplastic state, whereas if aided they form neoplasms. The deviations from the normal represented by the benign tar tumors of rabbits are slight and limited in character, but further deviations in larger variety may be superimposed upon them, with result in malignant tumors, growths possessed of a greater, though not always absolute, independence. Tar cancers usually come about in this way, by successive, step-like deviations from the normal, and so also do
Hepatic small vessel neoplasm, a rare infiltrative vascular neoplasm of uncertain malignant potential☆,☆☆
Gill, Ryan M.; Buelow, Benjamin; Mather, Cheryl; Joseph, Nancy M.; Alves, Venancio; Brunt, Elizabeth M.; Liu, Ta-Chiang; Makhlouf, Hala; Marginean, Celia; Nalbantoglu, ILKe; Sempoux, Christine; Snover, Dale C.; Thung, Swan N.; Yeh, Matthew M.; Ferrell, Linda D.
Summary Characteristic but rare vascular neoplasms in the adult liver composed of small vessels with an infiltrative border were collected from an international group of collaborators over a 5-year period (N = 17). These tumors were termed hepatic small vessel neoplasm (HSVN), and the histologic differential diagnosis was angiosarcoma (AS). The average age of patients was 54 years (range, 24–83 years). HSVN was more common in men. The average size was 2.1 cm (range, 0.2–5.5 cm). Diagnosis was aided by immunohistochemical stains for vascular lineage (CD31, CD34, FLI-1), which were uniformly positive in HSVN. Immunohistochemical stains (p53, c-Myc, GLUT-1, and Ki-67) for possible malignant potential are suggestive of a benign/low-grade tumor. Capture-based next-generation sequencing (using an assay that targets the coding regions of more than 500 cancer genes) identified an activating hotspot GNAQ mutation in 2 of 3 (67%) tested samples, and one of these cases also had a hotspot mutation in PIK3CA. When compared with hepatic AS (n = 10) and cavernous hemangioma (n = 6), the Ki-67 proliferative index is the most helpful tool in excluding AS, which demonstrated a tumor cell proliferative index greater than 10% in all cases. Strong p53 and diffuse c-Myc staining was also significantly associated with AS but not with HSVN or cavernous hemangioma. There have been no cases with rupture/hemorrhage, disseminated intravascular coagulation, or Kasabach-Merritt syndrome. Thus far, there has been no metastasis or recurrence of HSVN, but complete resection and close clinical follow-up are recommended because the outcome remains unknown. PMID:27090685
Comparative morphology of the gallbladder and biliary tract in vertebrates: variation in structure, homology in function and gallstones.
Oldham-Ott, C K; Gilloteaux, J
A review of investigations on the morphology of the gallbladder and biliary tract in fish, reptiles, amphibians, birds, and mammals was performed. Scanning electron microscopy, transmission electron microscopy, and light microscopy observations by the authors were also included. Variations in the presence or absence of a gallbladder, surface epithelium of the gallbladder, and differences in the morphology of the biliary tract in vertebrates were reported. Many differences were diet-related. Despite some dissimilarities observed, analogous functioning of the biliary system was accomplished by its various components, with the biliary ducts performing the function of the gallbladder when this organ was absent. In addition, the occurrence of peculiar parasitism and gallstones among some cases of vertebrates, including humans, was presented.
Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis.
Sun, Hong-Li; Han, Bing; Zhai, Hong-Peng; Cheng, Xin-Hua; Ma, Kai
Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR = 1.13, 95% CI 0.88-1.46, P = 0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR = 1.46, 95% CI 1.02-2.09, P = 0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.
An Unusual Case of Gastrointestinal Bleeding from Isolated Gallbladder Varices in a Patient with Pancreatic Cancer Complicated by Portal Biliopathy
Kubachev, Kubach; Abdullaev, Elbrus; Zarkua, Nonna; Abdullaev, Abakar; Fokin, Artur
Portal biliopathy is the complex of abnormalities of extrahepatic and intrahepatic bile ducts, cystic duct, and gallbladder, arising as a result of extrahepatic portal vein obstruction and noncirrhotic portal fibrosis, which can be caused by coagulopathies, tumors, inflammation, postoperative complications, dehydration, and neonatal umbilical vein catheterization. We report a case of a 55-year-old male patient with the history of pancreatic cancer and cholecystoenteric anastomosis presenting with gastrointestinal bleeding from gallbladder varices via the anastomosis. PMID:27800195
Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms
Grinfeld, Jacob; Nangalia, Jyoti; Green, Anthony R.
The myeloproliferative neoplasms are a heterogeneous group of clonal disorders characterized by the overproduction of mature cells in the peripheral blood, together with an increased risk of thrombosis and progression to acute myeloid leukemia. The majority of patients with Philadelphia-chromosome negative myeloproliferative neoplasms harbor somatic mutations in Janus kinase 2, leading to constitutive activation. Acquired mutations in calreticulin or myeloproliferative leukemia virus oncogene are found in a significant number of patients with essential thrombocythemia or myelofibrosis, and mutations in numerous epigenetic regulators and spliceosome components are also seen. Although the cellular and molecular consequences of many of these mutations remain unclear, it seems likely that they interact with germline and microenvironmental factors to influence disease pathogenesis. This review will focus on the determinants of specific myeloproliferative neoplasm phenotypes as well as on how an improved understanding of molecular mechanisms can inform our understanding of the disease entities themselves. PMID:27909216
[Pathologic characteristics of malignant neoplasms occurring in the elderly].
Arai, Tomio; Matsuda, Yoko; Aida, Junko; Takubo, Kaiyo
Malignant neoplasm preferentially occurs in the elderly. Common cancers in the elderly are gastric, colorectal, lung and prostate cancers in men whereas colorectal, lung, gastric and pancreatic cancers in women. There are several characteristic features such as tumor location, histology, biological behavior and pathway of carcinogenesis in malignant neoplasms occurring in the elderly. Multiple cancers increase with aging. Although it is generally believed that carcinoma in the elderly shows well differentiation, slow growth, low incidence of metastasis and favorable prognosis, the tumor does not always show such features. Regarding biological behavior of malignant tumor in the elderly, age-related alterations of the host such as stromal weakness and decreased immune response against cancer cell invasion should be considered as well as characteristics of tumor cell itself. Thus, we need a specific strategy for treatment for malignant neoplasms in the elderly.
The role of JAK2 abnormalities in hematologic neoplasms
Alabdulaali, Mohammed K.
In 2005, an activating mutation in the Janus kinase 2 (JAK2) was identified in a significant proportion of patients with myeloproliferative neoplasms, mainly polycythemia vera, essential thrombocythemia and primary myelofibrosis. Many types of mutations in the JAK-STAT pathway have been identified, the majority are related to JAK2. Currently JAK2 mutations are important in the area of diagnosis of myeloid neoplasms, but its role beyond the confirmation of clonality is growing and widening our knowledge about these disorders. In addition to that, clinical trials to target JAK2-STAT pathway will widen our knowledge and hopefully will offer more therapeutic options. In this review, we will discuss the role of JAK2 abnormalities in the pathogenesis, diagnosis, classification, severity and management of hematologic neoplasms.
Identification of the most common cutaneous neoplasms in dogs and evaluation of breed and age distributions for selected neoplasms.
Villamil, J Armando; Henry, Carolyn J; Bryan, Jeffrey N; Ellersieck, Mark; Schultz, Loren; Tyler, Jeff W; Hahn, Allen W
OBJECTIVE-To identify the most common cutaneous neoplasms in dogs and evaluate breed and age distributions for selected neoplasms. DESIGN-Retrospective epidemiological study. SAMPLE-Records available through the Veterinary Medical Database of dogs examined at veterinary teaching hospitals in North America between 1964 and 2002. PROCEDURES-Information on tumor type and patient breed and age was collected. Incidence and odds ratios with 95% confidence intervals were calculated. RESULTS-Records of 1,139,616 dogs were reviewed. Cutaneous neoplasms were diagnosed in 25,996 of these dogs; records for the remaining 1,113,620 dogs did not indicate that cutaneous neoplasms had been diagnosed, and these dogs were considered controls. The most frequent age range for dogs with cutaneous neoplasms was 10 to 15 years. Lipoma, adenoma, and mast cell tumor were the most common skin tumor types. CONCLUSIONS AND CLINICAL RELEVANCE-Results supported previously reported data regarding cutaneous neoplasia in dogs but provided updated information on the most common skin tumors and on age and breed distributions.
Disseminated encephalomyelitis-like central nervous system neoplasm in childhood.
Zhao, Jianhui; Bao, Xinhua; Fu, Na; Ye, Jintang; Li, Ting; Yuan, Yun; Zhang, Chunyu; Zhang, Yao; Zhang, Yuehua; Qin, Jiong; Wu, Xiru
A malignant neoplasm in the central nervous system with diffuse white matter changes on magnetic resonance imaging (MRI) is rare in children. It could be misdiagnosed as acute disseminated encephalomyelitis. This report presents our experience based on 4 patients (3 male, 1 female; aged 7-13 years) whose MRI showed diffuse lesions in white matter and who were initially diagnosed with acute disseminated encephalomyelitis. All of the patients received corticosteroid therapy. After brain biopsy, the patients were diagnosed with gliomatosis cerebri, primitive neuroectodermal tumor and central nervous system lymphoma. We also provide literature reviews and discuss the differentiation of central nervous system neoplasm from acute disseminated encephalomyelitis.
Dermatomyositis as the first manifestation of gallbladder adenocarcinoma: case report and literature overview.
Jurcic, Petra
Dermatomyositis (DM) is characterized by pathognomic cutaneous manifestations (heliotrope rash, periorbital edema, Gottron's papules) and proximal muscle weakness. In this paper, I will present the case of a 48-year-old female patient whose dermatomyositis was initially diagnosed as vasculitis. Following the patient's inadequate response to corticosteroid treatment, clinical and radiologic examinations were performed, showing inoperable gallbladder adenocarcinoma. Although initial chemotherapy led to regression, the dermatomyositis developed an independent course with new pathological changes leading to the progression of the disease. I will also present an overview of case reports in English published so far. Gallbladder carcinoma should be added to the list of malignancies with dermatomyositis and has to be excluded by relevant investigation in women.
Further evidence for the heterogeneity of functional muscarinic receptors in guinea pig gallbladder.
Akici, A; Karaalp, A; Iskender, E; Christopoulos, A; El-Fakahany, E E; Oktay, S
Previous studies have suggested the presence of multiple muscarinic receptor subtypes in guinea pig gallbladder smooth muscle, although the relative abundance and functional role of these subtypes remains an area of significant research efforts. The present study utilized both radioligand kinetic and functional experiments to further probe the nature of the muscarinic receptors in gallbladder smooth muscle and their mode of coupling to intra- and extra-cellular Ca(2+) sources. Dissociation kinetic studies using [3H]N-methylscopolamine ([3H]NMS) indicated that the binding profile in guinea pig gallbladder smooth muscle could not be reconciled with that expected for a single muscarinic receptor subtype, the latter determined in parallel experiments conducted on the cloned muscarinic M(1)-M(5) subtypes in Chinese hamster ovary (CHO) cells. Furthermore, comparison of the gallbladder data with the dissociation characteristics of [3H]NMS in guinea pig urinary bladder revealed a significantly different kinetic profile, with the urinary bladder, but not the gallbladder, demonstrating biphasic radioligand dissociation kinetics. In functional experiments, carbachol caused a concentration-dependent contraction of guinea pig gallbladder smooth muscle strips in Ca(2+)-free or 5 mM Sr(2+)-substituted physiological salt solutions (PSS) with amplitudes of the maximal contractions corresponding to 45.8+/-8.0% and 33.2+/-6.6% of control responses in normal PSS, respectively. Furthermore, the stimulus-response characteristics of carbachol-mediated contraction appeared significantly altered in Ca(2+)-free PSS relative to normal or Sr(2+)-substituted PSS. The antagonist, methoctramine (1x10(-7)-3x10(-5) M), exerted only a slight inhibition of carbachol (10(-5) M)-induced contractions in 5 mM Sr(2+)-substituted medium, whereas it was significantly more potent in antagonizing gallbladder contractions in response to 10(-5) M carbachol in the absence of extracellular Ca(2+). Both atropine
Ultrastructure of Myxidium trachinorum sp. nov. from the gallbladder of the lesser weever fish Echiichthys vipera.
Canning, E U; Curry, A; Anderson, C L; Okamura, B
Myxidium trachinorum sp. nov. is described from the gallbladder of the lesser weever fish Echiichthys vipera. Pseudoplasmodia attach themselves to the gallbladder epithelium by filose processes, which are inserted between host cells. Pseudoplasmodia undergo endogenous cell formation at the secondary and tertiary levels. In the proliferative cycle, primary and endogenous cells are packed with digestive vacuoles formed by phagocytosis. In the sporogonic cycle the pseudoplasmodium becomes a pericyte enclosing two secondary cells (lacking digestive vacuoles) in a vacuole. These give rise to five cells each two valvogenic, two capsulogenic and a binucleate sporoplasm, which mature into spores. Comparison of the disporic M. trachinorum with polysporic species of Myxidium revealed significant differences in plasmodial ultrastructure, especially their attachments to host cells, surface characteristics and mode of nutrition, and in formation of generative cells. These suggest that the genus Myxidium may require revision.
Congenital absence of the gallbladder: another cause of false-positive hepatobiliary image
Dickinson, C.Z.; Powers, T.A.; Sandler, M.P.; Partain, C.L.
Hepatobiliary imaging with the various technetium-labeled IDA compounds is more than 90% sensitive and specific for the diagnosis of acute cholecystitis. Causes of false-positive studies include chronic cholecystitis, cystic-duct obstruction by tumor, prolonged fasting, the nonfasting state, pancreatitis, alcoholism, parenteral hyperalimentation, and severe intercurrent illness. A case of congenital absence of the gallbladder is sumbitted as another cause of a false-positive scan.
Long-term culture and partial characterization of dog gallbladder epithelial cells
Oda, D.; Lee, S.P.; Hayashi, A. )
We describe the successful isolation and maintenance of primary cultures of dog gallbladder epithelial cells. The surgically removed gallbladder was treated with trypsin/EDTA for 45 minutes and epithelial cells were collected and resuspended in Eagle's minimum essential medium with 10% fetal calf serum, and plated on Vitrogen-coated culture dishes. Each gallbladder yielded approximately 12 to 15 x 10{sup 6} columnar epithelial cells, greater than 95% of which were viable by trypan blue exclusion. In culture, cells maintained their polarity. They were arranged and grew in small and tight clusters that coalesced at confluency. When examined using transmission electron microscopy, prominent and numerous microville were identified on the apical portion of the plasma membrane. Cells were connected by well-formed desmosomes. Scanning electron microscopy revealed clusters of polyhedral cells with numerous papillary projections. Immunohistochemical studies demonstrated uniform staining of cells to keratin 35BH11 and AE1. Histochemical studies were positive for gamma-glutamyl transpeptidase and negative for glucose-6-phosphatase and albumin. Cells incorporated ({sup 3}H)uridine into intracellular proteins and ({sup 14}C)glucosamine into tissue and secreted mucous glycoproteins linearly over 2 to 24 hours. Flow cytometry studies demonstrated a consistent and reproducible number of cells (10 to 12%) at S-phase. However, the number of cells at S-phase was dramatically reduced to almost negligible as cells reached confluency. This method of culturing primary dog gallbladder epithelial cells is highly reproducible and reliable. These cells preserve their state of differentiation, polarity, histochemical and immunohistochemical profile, morphologic, and metabolic integrity with repeated passaging or after being frozen.
A comparative study of mud-like and coralliform calcium carbonate gallbladder stones.
Ma, Rui-Hong; Luo, Xiao-Bing; Wang, Xiao-Feng; Qiao, Tie; Huang, Hai-Yi; Zhong, Hai-Qiang
To gain insight to underlying mechanism of the formation of calcium carbonate (CaCO3 ) gallbladder stones, we did comparative study of stones with mud appearance and those with coralliform appearance. A total of 93 gallbladder stones with mud appearance and 50 stones with coralliform appearance were analyzed. The appearance, color, texture, and the detection of Clonorchis sinensis eggs by microscopic examination were compared between the two groups. Then, the material compositions of stones were analyzed using Fourier Transform Infrared spectroscopy and the spectrogram characteristics were compared. Moreover, microstructure characteristics of the two kinds of stones were observed and compared with Scanning Electron Microscopy. Mud-like gallbladder stones were mainly earthy yellow or brown with brittle or soft texture, while coralliform stones were mainly black with extremely hard texture, the differences between the two groups was significant (p < .05). The analytic results of FTIR spectroscopy showed that 95.7% (89/93) of the mud-like gallbladder stones were CaCO3 stones, and mainly aragonite; while all of the coralliform stones were CaCO3 stones, and mainly calcite (p < .05). Meanwhile, microscopic examination indicated that the detection rate of Clonorchis sinensis eggs in mud-like CaCO3 stones was lower than that in coralliform CaCO3 stones (p < .05), and that in aragonite CaCO3 stones was lower than that in calcite CaCO3 stones(p < .05). Mud-like CaCO3 stones mainly happened to patients with cystic duct obstruction. Clonorchis sinensis infection was mainly associated with coralliform (calcite) CaCO3 stones. Cystic duct obstruction was mainly associated with mud-like (aragonite) CaCO3 stones.
Standards of the Polish Ultrasound Society - update. The liver, gallbladder and bile ducts examinations.
Walas, Maria Krystyna; Skoczylas, Krzysztof; Gierbliński, Ireneusz
Ultrasonography, which usually constitutes an initial imaging method of the gallbladder, liver and bile ducts diseases, allows for final diagnosis or determines another diagnostic step. The continuously progressing technological advancement forces to broaden the indications for ultrasound diagnostics and enables easier and more precise imaging of the tested structures. Performing the examination in accordance with current standards allows for the optimization of the sensitivity and specificity parameters of ultrasound examinations in the diagnosis of the liver, gallbladder and bile ducts pathologies as well as minimizes the probability of error-making. This article presents a recommended liver, gallbladder and bile ducts ultrasound technique which indicates an optimal positioning of the patient for the exam as well as the sites of the ultrasound transducer application. Minimum technical parameters of the apparatus have been specified with respect to the requirements of modern ultrasound techniques which enable imaging with the use of contrast agents and elastography. Furthermore, the article proposes a standard exam description containing essential patient-related data and provides required ultrasound evaluation parameters for the tested organs. Attention has been drawn to the appropriate manner of preparing the patient for the examination and the features of the tested structures have been presented. The article also contains a brief description of the liver, gallbladder and bile ducts diseases which are most often diagnosed by ultrasound examinations. Moreover, the use of elastography as well as contrast-enhanced examinations in the diagnostics of fibrosis and focal changes in the liver have been discussed. This article has been prepared on the basis of the Ultrasound Examination Standards of the Polish Ultrasound Society (2011) and updated with reference to the latest findings in pertinent literature.
Sluggish gallbladder emptying and gastrointestinal transit after intake of common alcoholic beverages.
Kasicka-Jonderko, A; Jonderko, K; Gajek, E; Piekielniak, A; Zawislan, R
To study the movement along the gut and the effect upon the gallbladder volume of alcoholic beverages taken in the interdigestive state. The study comprised three research blocks attended by 12 healthy subjects each. Within a given research block volunteers underwent three examination sessions held on separate days, being offered an alcoholic beverage, or an aqueous ethanol solution of an identical proof, or a corresponding volume of isotonic glucose solution; the order of administration of the drinks was randomized. The beverages tested were: beer (4.7% vol, 400 ml), red wine (13.7% vol, 200 ml), whisky (43.5% vol, 100 ml) within the "Beer", "Wine", and "Whisky" research block, respectively. Gastric myoelectrical activity was examined electrogastrographically, gastric emptying with ¹³C-sodium acetate breath test, orocaecal transit with lactulose H₂ breath test, gallbladder emptying with ultrasonography, breath ethanol with alcotest. The study showed that alcoholic beverages were emptied from the stomach significantly slower than isotonic glucose. Alcoholic beverages produced by fermentation only (beer, red wine) were emptied from the stomach more slowly than ethanol solutions of identical proof, while gastric evacuation of whisky (distillation product) and matching alcohol solution was similar. The slower gastric evacuation of alcoholic beverages and ethanol solutions could not be ascribed to a disorganization of the gastric myoelectrical activity. The orocaecal transit of beer and red wine did not differ from that of isotonic glucose, whereas the orocaecal transit of whisky and high proof ethanol was markedly prolonged. Red wine and whisky, and to a similar extent control ethanol solutions caused an inhibition and delay of gallbladder emptying. We concluded that alcoholic beverages taken on an empty stomach exert a suppressive effect upon the transport function of the digestive tract and gallbladder emptying. The extent of this action depends on the type of a
Role of cytosolic phospholipase A2 in cytokine-stimulated prostaglandin release by human gallbladder cells.
Grossmann, E M; Longo, W E; Mazuski, J E; Panesar, N; Kaminski, D L
Eicosanoids are involved in gallbladder inflammation, epithelial water transport, and mucous secretion. Phospholipase Asubscript2 enzymes liberate arachidonic acid from membrane phospholipids for the synthesis of eicosanoids. The purpose of this study was to determine the effect of selective cytoplasmic and secretory phospholipase A2 inhibitors on basal and stimulated arachidonic acid and prostaglandin E2 release in gallbladder cells. Western immunoblotting was employed to evaluate both cytosolic and secretory phospholipase A2 enzymes in human gallbladder cells. Cells were incubated for 22 hours with (3)H-labeled arachidonic acid. Arachidonic acid and prostaglandin E2 release was then measured in the supernate after 2 hours of exposure to human interleukin-1beta, alone or after pretreatment for 1 hour with the inhibitors. Unstimulated gallbladder cells express both 85 kDa cytosolic and 14 kDa secretory phospholipase A2++. The 85 kDa phospholipase A2 was induced by interleukin-1beta, whereas there was no apparent change in secretory phospholipase A2 enzyme concentrations. Both the secretory phospholipase A2 inhibitor p-bromophenylacyl bromide and the cytosolic phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone decreased basal and interleukin-1beta-stimulated arachidonic acid release. In contrast, only inhibition of cytosolic phospholipase A2 led to a decrease in interleukin-1beta-stimulated prostaglandin E2 release. Basal and interleukin-1beta-stimulated arachidonic acid release appears to be the result of the activity of both cytosolic and secretory phospholipase A2. Interleukin-1beta-stimulated prostaglandin E2 release appears to be dependent on the activity of cytosolic phospholipase A2.
[Macro-microscopic comparative study of gallbladder lesions in La Plata (Argentina)].
Corrons, F J; Sidoti Hartmann, A N; Castelletto, R H
The histogenesis of the gallbladder carcinoma is under controversy Some authors emphasize the polyp-cancer sequence, whereas others relate the adenocarcinoma with metaplastic and dysplastic changes. It is important to examine immediately the characteristics of the mucosa, in order for guidance to the surgeon at the operating room. With the purpose of correlating the macro-microscopic findings of gallbladder lesions, we studied 306 gallbladder specimens extended and fixed in formaline. We considered: Age, sex, lithiasis, dimensions of the specimens and macroscopic patterns of the mucosal surface. Longitudinal samples were taken for histological examination. Two hundred and thirty seven cases corresponded to female sex (77.4%) and 69 to male sex (22.5%) with an average age of 44 years. Among the microscopic findings, we found gastric metaplasia in 43% of the cases, intestinal metaplasia in 10.8%, low grade dysplasia in 11.8% and high grade dysplasia in 1.6%, and 2 cases of clinically unsuspected invasive carcinomas (0.6%). An association between chronic colecistitis, lithiasis and epithelial changes was confirmed, but the relation between each one of the macroscopic patterns proposed and the histological findings is statistically significant only in the cases of atrophy, probably owing to the overlapping of microscopic findings in the different macroscopic patterns.
Combined neuroendocrine cell carcinoma and adenocarcinoma of the gallbladder: report of a case.
Shimizu, Tetsuya; Tajiri, Takashi; Akimaru, Koho; Arima, Yasuo; Yoshida, Hiroshi; Yokomuro, Shigeki; Mamada, Yasuhiro; Taniai, Nobuhiko; Mizuguchi, Yoshiaki; Kawahigashi, Yutaka; Naito, Zenya
A 58-year-old man with a chief complaint of epigastralgia was admitted to our hospital. Physical examination disclosed a large, firm mass in the right hypochondrium. Abdominal computed tomography confirmed thickening of the gallbladder wall and a 15 x 8 cm mass occupying almost all of the right lobe and medial segment of the liver. With a preoperative diagnosis of malignant gallbladder tumor infiltrating the liver, right hepatic trisegmentectomy was performed. Histopathologic examination showed atypical cells with small round to oval nuclei and sparse eosinophilic cytoplasm, proliferating in a solid and focal nesting pattern. Near this small cell proliferation was a focus of tubular adenocarcinoma that showed a zone of transition from the small cell neuroendocrine pattern. The small cells demonstrated immunohistochemical reactivity for chromogranin A. Electron microscopy disclosed neurosecretory granules 150 nm in diameter, representing dense round core vesicles, confirming a neuroendocrine cell lineage. The patient was diagnosed with neuroendocrine cell carcinoma combined with adenocarcinoma of the gallbladder. Tumor recurrence became evident 3 months after surgery, and he died 4 months after surgery.
Oxysterols from human bile induce apoptosis of canine gallbladder epithelial cells in monolayer culture.
Seo, Dong Wan; Choi, Ho-Soon; Lee, Sum P; Kuver, Rahul
Oxysterols have been detected in various mammalian organs and blood. Biliary epithelium is exposed to high concentrations of cholesterol, and we have identified three keto-oxysterols (cholest-4-en-3-one, cholesta-4,6-dien-3-one, cholesta-3,5-dien-7-one) in human bile and gallstones. Because the effects of oxysterols on biliary physiology are not well defined, we investigated their biological effects on dog gallbladder epithelial cells. Enriched medium (culture medium containing taurocholate and lecithin and cholesterol +/- various oxysterols) was applied to confluent monolayers of dog gallbladder epithelial cells in culture. Cytotoxicity and apoptosis were studied by morphological analysis and flow cytometry. Oxysterols in the mitochondrial fraction were identified by gas chromatography/mass spectrometry, whereas release of cytochrome c from mitochondria was assayed by spectrophotometry and Western blot analysis. Compared with cells treated with culture medium or with enriched medium containing cholesterol, oxysterol-treated cells showed significantly increased apoptosis (P < 0.05). Exogenously applied oxysterols were recovered from the mitochondrial fraction. Cytochrome c release from mitochondria was increased significantly by cholest-4-en-3-one, cholesta-4,6-dien-3-one, and 5beta-cholestan-3-one (all P < 0.05). Thus oxysterols recovered from human bile and gallstones induce apoptosis of biliary epithelium via a mitochondrial-dependent pathway and may play a role in the pathogenesis of chronic inflammation and carcinogenesis in the gallbladder.
Monoclonal Antibodies to the Apical Chloride Channel in Necturus Gallbladder Inhibit the Chloride Conductance
NASA Astrophysics Data System (ADS)
Finn, Arthur L.; Tsai, Lih-Min; Falk, Ronald J.
Monoclonal antibodies raised by injecting Necturus gallbladder cells into mice were tested for their ability to inhibit the apical chloride conductance induced by elevation of cellular cAMP. Five of these monoclonal antibodies bound to the apical cells, as shown by indirect immunofluorescence microscopy, and inhibited the chloride conductance; one antibody that bound only to subepithelial smooth muscle, by indirect immunofluorescence microscopy, showed no inhibition of chloride transport. The channel or a closely related molecule is present in the membrane whether or not the pathway is open, since, in addition to inhibiting the conductance of the open channel, the antibody also bound to the membrane in the resting state and prevented subsequent opening of the channel. The antibody was shown to recognize, by ELISA, epitopes from the Necturus gallbladder and small intestine. Finally, by Western blot analysis of Necturus gallbladder homogenates, the antibody was shown to recognize two protein bands of Mr 219,000 and Mr 69,000. This antibody should permit isolation and characterization of this important ion channel.
[A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma].
Shinmura, Kazuyasu; Kaiho, Takashi; Yanagisawa, Shinji; Okamoto, Ryo; Nishimura, Masaki; Kobayashi, Soichi; Okaniwa, Akira; Mun, Yangi; Tsuchiya, Shunichi; Chiba, Ryoji
A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma.
Cutaneous metastasis of ovarian carcinoma with shadow cells mimicking a primary pilomatrical neoplasm.
Lalich, Daniel; Tawfik, Ossama; Chapman, Julia; Fraga, Garth
Shadow cells are characteristic of pilomatricoma, although they have been described in other cutaneous and visceral neoplasms, particularly endometrioid adenocarcinomas of the female genital tract. We describe a metastasis of an ovarian endometrioid adenocarcinoma with shadow cells to the skin that was initially misinterpreted as a pilomatricoma. We compare the histology of the ovarian neoplasm to 21 pilomatricomas. This is the first reported case of a cutaneous metastasis of a visceral neoplasm mimicking a primary pilomatrical neoplasm.
Serous cystic neoplasms of the pancreas: clinicopathologic and molecular characteristics.
Reid, Michelle D; Choi, Hyejeong; Balci, Serdar; Akkas, Gizem; Adsay, Volkan
We herein summarize the pathology and most recent advances in the molecular genetics of serous cystic neoplasms of the pancreas. They typically present as relatively large, well-demarcated tumors (mean size, 6cm), predominantly occurring in females. Pre-operative diagnosis remains challenging; imaging findings and cyst fluid analysis often prove non-specific and fine-needle aspiration often does not yield diagnostic cells. Pathologically, they are characterized by a distinctive cytology referred to as "serous." Although they have ductal differentiation, they distinctly lack the mucin production that characterizes most other pancreatic ductal tumors, including ductal adenocarcinoma and its variants, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). They instead produce abundant glycogen (glycogen-rich adenoma). Serous cystadenomas also lack the molecular alterations that characterize ductal neoplasms, such as mutation of KRAS (high prevalence in most mucinous ductal neoplasms), inactivation of SMAD4 (seen in ductal adenocarcinomas), and mutations in GNAS (seen in some IPMNs) and RNF43 (detected in MCNs and IPMNs). Instead, new molecular and immunohistochemical observations place serous pancreatic tumors closer to "clear cell neoplasms" seen in various other organs that are associated with the von Hippel-Lindau (VHL) pathway, such as clear cell renal cell carcinomas and capillary hemangioblastomas. Patients with VHL syndrome have an increased risk of developing serous pancreatic tumors and somatic mutations of the VHL gene are common in these tumors along with modification of its downstream effectors including hypoxia-inducible factor (HIF1), glucose uptake and transporter-1 (GLUT-1), a common factor in clear cell (glycogen-rich) tumors, as well as expression of vascular endothelial growth factor (VEGF), thought to be a factor in the striking capillarization of serous cystadenomas and other non-pancreatic clear cell tumors. VEGF may
Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children
We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491
Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous "black" pigment gallstone formation in germfree Swiss Webster mice.
Woods, Stephanie E; Leonard, Monika R; Hayden, Joshua A; Brophy, Megan Brunjes; Bernert, Kara R; Lavoie, Brigitte; Muthupalani, Sureshkumar; Whary, Mark T; Mawe, Gary M; Nolan, Elizabeth M; Carey, Martin C; Fox, James G
"Black" pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates ("hyperbilirubinbilia") from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and <1% cholesterol, and had low-grade inflammation, edema, and epithelial hyperplasia. Hemograms were normal, but serum cholesterol was elevated in GF compared with SPF SW mice, and serum glucose levels were positively related to increasing age. Aged GF and SPF SW mice had deficits in gallbladder smooth muscle activity. In response to cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.
Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study
Andia, Marcelo E.; Hsing, Ann W.; Andreotti, Gabriella; Ferreccio, Catterina
Chile's gallbladder cancer rates are among the highest in the world, being the first cancer killer among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer (relative to the national average mortality rate) between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex, and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region (costal, inland, northern, and southern), poverty, Amerindian (Mapuche) population, typhoid fever, and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, age-sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants, being higher in inland and southern regions; compare to the north-coastal, the northern-inland region had a 10-fold risk odds ratio (OR) (95% of confidence interval (95% CI): 2.4–42.2) and the southern-inland region had a 26-fold risk (OR 95%CI: 6.0–114.2). Independent risk factors for gallbladder cancer were: ethnicity (Mapuche) OR:3.9 (95%CI 1.8–8.7), typhoid fever OR:2.9 (95%CI 1.2–6.9), poverty OR:5.1 (95%CI 1.6–15.9), low access to cholecystectomy OR:3.9 (95%CI 1.5–10.1), low access to hospital care OR:14.2 (95%CI 4.2–48.7) and high urbanization OR:8.0 (95%CI 3.4–18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology. PMID:18566990
Low prevalence of Helicobacteraceae in gall-stone disease and gall-bladder carcinoma in the German population.
Bohr, U R M; Kuester, D; Meyer, F; Wex, T; Stillert, M; Csepregi, A; Lippert, H; Roessner, A; Malfertheiner, P
Colonisation of the hepatobiliary system with bile-resistant Helicobacter spp. has been proposed as a novel risk-factor in the pathogenesis of gall-bladder carcinoma (GBC). There are reports that biliary Helicobacter colonisation is frequent in countries with a high incidence of gall-bladder carcinoma. However, the prevalence of Helicobacteraceae in the gall-bladders of patients with GBC in Germany, a region with a low incidence of GBC, is unknown. Therefore, gall-bladder tissue from 99 patients who had undergone cholecystectomy was tested, including 57 cases of gall-stone disease (GSD), 20 cases of GBC, and 22 control patients. The presence of Helicobacter spp. was investigated by culture, immunohistochemistry and a group-specific PCR targeting the 16S rRNA gene of all currently known Helicobacteraceae. Of the 99 cases investigated, only one patient with GSD was PCR-positive for Helicobacteraceae. For this individual, sequence analysis of the 16S rRNA gene showed that it had homology closest to the 16S rRNA sequence of Helicobacter ganmani. Helicobacteraceae were not detected by culture or immunohistochemistry. The low prevalence of Helicobacteraceae in the gall-bladders investigated suggests that Helicobacteraceae do not play a predominant role in the pathogenesis of GSD and GBC in the German population. The low prevalence could be a possible explanation for a relatively low incidence of GBC in the German population, despite the fact that GSD, the major risk-factor for GBC, is highly prevalent.
Gallbladder Volvulus in a Patient with Type I Choledochal Cyst: A Case Report and Review of the Literature
Younan, George; Schumm, Max
Introduction. Gallbladder volvulus is a rare, potentially fatal condition unless diagnosed and treated early. Choledochal cysts are rare congenital malformations of the biliary tree predisposing to different pathologies and posing the risk of degradation into cholangiocarcinoma and gallbladder cancer. Dealing with both diseases at once has not been published yet in the literature. Presentation of Case. We report a case of gallbladder volvulus in an elderly female who happened to have a concomitant type I choledochal cyst. Treatment was achieved with a cholecystectomy and observation and follow-up of the choledochal cyst. Discussion. Prompt diagnosis and surgical management of gallbladder volvulus is important to avoid the morbidity and mortality of gangrenous cholecystitis and biliary peritonitis in a frail old population of patients. Precise clinical diagnosis, supplemented with specific imaging clues, helps in the diagnosis. Management of choledochal cysts is also surgical; however the timing of surgery is still a matter of debate. Conclusion. We describe in this report the first case of gallbladder volvulus in a patient with a choledochal cyst and propose a management algorithm of a very rare biliary tree pathology combination. PMID:27747125
Second neoplasms following megavoltage radiation for pediatric tumors
McGuire, W.A.; Dusenbery, K.E.; Potish, R.A.
Because ionizing radiation is a known carcinogen, diligent long term follow-up; in children exposed to therapeutic radiation is required. Since 1954 a large cohort of children receiving megavoltage RT at the University of Minnesota have been closely followed, and we now update our previous reports on the nature and risk of second neoplasms in this patient population. We have followed 487 children who were treated with megavoltage radiation therapy (RT) between 1/1/1954 and 12/31/1980. Patients at the time of RT ranged in age from 2 weeks to 17 years (median 6.2 years) and were treated for a variety of benigh (n=39) and malignant (n=448) conditions. The most common indications for RT were ALL (n=160), primary brain tumors (n=79), Hodgkin`s Disease (n=56), Wilms Tumor (n=36), neuroblastoma (n=33), and Histiocytosis X (n=24). Median follow-up of surviving patients is 19.9 years (range 4.8 to 39.9 years) with a total of 9832 patient years of follow-up accrued. Only 14 (2.9%) of patients were lost to follow-up and were censored at the time of last follow-up. Kaplan Meier actuarial survival estimates for all patients was 93% (95% C.I.90-95%) at 20 years and 86% (95% C.I. 81-90.5%) at 30 years. Forty-two (8.6%) patients developed second neoplasms from 3.8 to 32 years (median 15 years) after RT. The cumulative risk of developing a second neoplasm was 17% at 20 years. The most common second neoplasms were breast cancer (n=8), meningiomas (n-6) and skin cancers (n=7), all of which were within the RT fields, and developed at a median of 18, 16 and 21 years after RT, respectively. Of the 42 patients with second neoplasms, 16 died either of the second neoplasm (n=15) or of recurrent primary tumor (n=1). Risk factors associated with developing a second malignancy included age >10 years at RT (p=0.009), and an initial diagnosis of Hodgkin`s Disease (p<0.0001).
Further investigations of the etiology of subcutaneous neoplasms in native gizzard shad (Dorosoma cepedianum)
Jacobs, A.D.; Ostrander, G.K.
Aspects of the etiology of subcutaneous spindle-cell neoplasms in feral gizzard shad (Dorosoma cepedianum) collected from Lake of the Arbuckles, Oklahoma, were investigated. Field collections of adult and juvenile gizzard shad were conducted to determine the prevalence and seasonality of neoplasms and site specificity of neoplasms-bearing fish. Overall neoplasm prevalence for adult gizzard shad was 22.1%; no juveniles exhibited neoplasms. Neoplasm occurrence did not appear seasonal. Neoplasm-bearing gizzard shad were found at all three sampling sites within Lake of the Arbuckles with similar neoplasm prevalence rates (Guy Sandy Creek 22.1%, Rock creek, 17.9%, and Buckhorn Creek 22.4%). No gizzard shad (juvenile or adult) collected from Lake Carl Blackwell, Oklahoma, the reference site, exhibited neoplasms. Water, sediment, and shad liver tissue from Lake of the Arbuckles and the reference site were analyzed for total recoverable metals (cadmium, chromium, copper, nickel, and lead, by graphite furnace atomic absorption). Chromium, copper, and nickel were found in the water samples at concentrations of >1 to 8.6 {micro}g/L. Low concentrations (>1 to 13.6 {micro}g/g wet weight) of all the metals were found in the sediment and liver tissue for both sites. Heavy metal contamination does not appear linked to neoplasm occurrence. To determine if a nonbacterial infectious agent was responsible for tumor formation, cell-free neoplasm homogenates were injected into healthy rainbow trout. Neoplasms were not transmitted into rainbow trout. Neoplasms were not transmitted into rainbow trout. The etiology of these neoplasms remains unknown.
Lesions and Neoplasms of the Penis: A Review.
Heller, Debra S
In addition to practitioners who care for male patients, with the increased use of high-resolution anoscopy, practitioners who care for women are seeing more men in their practices as well. Some diseases affecting the penis can impact on their sexual partners. Many of the lesions and neoplasms of the penis occur on the vulva as well. In addition, there are common and rare lesions unique to the penis. A review of the scope of penile lesions and neoplasms that may present in a primary care setting is presented to assist in developing a differential diagnosis if such a patient is encountered, as well as for practitioners who care for their sexual partners. A familiarity will assist with recognition, as well as when consultation is needed.
Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms
Atallah, Ehab; Verstovsek, Srdan
The discovery of the Janus kinase (JAK)2 V617F mutation in patients with myeloproliferative neoplasms was a major milestone in understanding the biology of those disorders. Several groups simultaneously reported on the high incidence of this mutation in patients with myeloproliferative neoplasms: almost all patients with polycythemia vera harbor the mutation and about 50% of patients with essential thrombocythemia and primary myelofibrosis have the mutation, making the development of JAK2 tyrosine kinase inhibitors an attractive therapeutic goal. In addition, inhibition of JAK2 kinase may have a therapeutic role in other hematologic malignancies, such as chronic myeloid leukemia or lymphoma. A number of molecules that inhibit JAK2 kinase have been described in the literature, and several are being evaluated in a clinical setting. Here, we summarize current clinical experience with JAK2 inhibitors. PMID:19445582
Molecular pathogenesis of intraductal papillary mucinous neoplasms of the pancreas.
Thosani, Nirav; Dasari, Chandra S; Bhutani, Manoop S; Raimondo, Massimo; Guha, Sushovan
Over the last 3 decades, there have been substantial improvements in diagnostic imaging and sampling techniques to evaluate pancreatic diseases. The modern technology has helped us to recognize premalignant conditions of pancreas including mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMNs). Differentiation between benign and malignant lesions and early detection of any malignant transformation in premalignant lesion are extremely important for further management decisions. Diagnostic cytology has limited sensitivity to further differentiate between benign, premalignant, and malignant lesions of the pancreas. There is limited information about the epidemiological risk factors and molecular mechanisms leading to development and further progression to malignancy of IPMNs. Several studies have shown that pancreatic juice and pancreatic tissue from the lesion can be tested for molecular markers including K-ras, p53, and p16 to differentiate between cancer and chronic inflammatory process. We review cellular signaling pathways that contribute to pathogenesis of IPMNs of the pancreas to further identify potential biomarkers and molecular targets.
Secondary neoplasms after radiotherapy for a childhood solid tumor.
Paulino, Arnold C; Fowler, B Zach
This study was conducted to determine the outcome of patients who develop a second neoplasm after radiotherapy (RT) for a childhood solid tumor. From 1956 to 1998, 429 children with a malignant solid tumor were treated at a single radiation oncology facility. The medical records and radiotherapy charts were reviewed to determine if the patient developed a secondary neoplasm after treatment for malignancy. Twenty-three (5.4%) patients developed a secondary neoplasm. There were 12 males and 11 females with a median age at RT of 6.6 years (range, 2 months to 20 years). There were 14 malignant neoplasms in 13 (3.0%) and 14 benign neoplasms in 11 patients (2.6%). The types of initial solid tumors treated with RT were Ewing sarcoma in 6, Wilms tumor in 6, medulloblastoma in 5, neuroblastoma in 3, and other in 3. Median RT dose was 45 Gy (range, 12.3 to 60 Gy) using 4 MV in 9, 1.25 MV in 8, 250 KV in 4, and 6 MV photons in 1 patient. One child was treated using 15-MeV electrons. Fourteen had chemotherapy. Median follow-up was 23.2 years (range, 5.3 to 44.4 years). For the 14 malignant neoplasms, the median time interval from initial tumor to second malignancy was 10.1 years. The 14 second malignant neoplasms (SMN) were osteosarcoma in 3, breast carcinoma in 2, melanoma in 2, malignant fibrous histiocytoma in 1, dermatofibrosarcoma in 1, leiomyosarcoma in 1, mucoepidermoid carcinoma in 1, colon cancer in 1, chronic myelogenous leukemia in 1, and basal cell carcinoma in 1. Ten of the 14 SMN (71%) were at the edge or inside the RT field. The 5- and 10-year overall survival rate after diagnosis of an SMN was 69.2%; it was 70% for children with a SMN at the edge or inside the RT field and 66.7% for those outside of the RT field. The 14 benign neoplasms appeared at a median time of 16.9 years and included cervical intraepithelial neoplasia in 3, osteochondroma in 3, thyroid adenoma in 1, duodenal adenoma in 1, lipoma in 1, cherry angioma in 1, uterine leiomyoma in 1, ovarian
Neoplastic disease after liver transplantation: Focus on de novo neoplasms
Burra, Patrizia; Rodriguez-Castro, Kryssia I
De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma (HCC) recurrence have been reported with the use of mTOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs mTOR-inhibitor-free immunosuppression is more efficacious in reducing HCC recurrence. PMID:26269665
Epidemio-hygieological aspects of gastric neoplasms in aged patients.
Shibata, H; Hara, M; Makino, T; Kikuchi, K; Senoue, I; Nomiyama, T; Miwa, M; Suzuki, S; Harasawa, S; Tani, N; Miwa, T
A 100-year-old male who died of gastric carcinoma was discussed and illustrated epidemiohygieologically. According to dynamic population statistics of the Health and Welfare Ministry of Japan, 418 persons over the age of 100 years died in 1979. Among them, 157 (38%) died of cardiovascular diseases and 49 (12%) died of pulmonary diseases, but only six died of neoplasms including two with gastric carcinomas (0.48%). To our knowledge no such case has been reported previously in the literature.
US in preoperative evaluation of parotid gland neoplasms.
Gerwel, Agata; Kosik, Krzysztof; Jurkiewicz, Dariusz
Salivary gland neoplasms account for only 3% of all tumors of the head and neck area, but as they represent a wide variety of histological types, they are a big diagnostic challenge. The cornerstone of salivary gland neoplasm treatment, both for the benign and malignant lesions, is surgery. The main goal of the therapy is not only to achieve complete surgical tumor resection, but also to preserve adjacent structures (facial nerve, parapharyngeal space structures). Ultrasonography is an examination commonly used in the preoperative diagnosis of the lesions localized within salivary glands. Very often it is the only diagnostic imaging method used in these cases. The aim of the study was to establish diagnostic value of US examination and its parameters for the assessment of parotid gland tumors. A prospective study was performed on a group of 51 patients with parotid gland neoplasms, who over a period of 3 years underwent surgery in Otolaryngology and Laryngological Oncology Department with Craniomaxillofacial Surgery Department of Central Clinical Hospital of Ministry of Defence in Warsaw. All the included patients underwent US examination in the preoperative period. The parameters selected for the assessment were: ill-defined tumor margins, tumor vascularity and the presence of enlarged regional lymph nodes. The results of imaging examination were compared to the final diagnosis based on pathological examination of the surgical specimen. The parameters of the US examination such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the evaluation of parotid gland tumors were established based on the examination results. An analysis was performed and ill-defined parotid tumor margins turned out to be a US parameter with higher diagnostic value for differentiating benign and malignant lesions than increased tumor vascularity. The presence of enlarged regional lymph nodes with blurred echostructure on the US examination
GATA3 immunohistochemical expression in salivary gland neoplasms.
Schwartz, Lauren E; Begum, Shahnaz; Westra, William H; Bishop, Justin A
GATA3 is a zinc finger transcription factor that regulates the normal development of many tissues and cell types. Recent studies have shown that immunohistochemical nuclear staining for GATA3 among tumors is highly restricted to carcinomas of breast and urothelial origin; however salivary gland tumors have not been tested. Given that breast and salivary gland tissues are very similar with respect to embryologic development and structure, we performed GATA3 staining on a spectrum of salivary gland neoplasms. GATA3 immunohistochemistry was performed on a diverse collection of 180 benign and malignant salivary gland neoplasms including 10 acinic cell carcinomas, 2 adenocarcinomas not otherwise specified, 41 adenoid cystic carcinomas, 2 epithelial-myoepithelial carcinomas, 1 low grade cribriform cystadenocarcinoma, 15 mammary analogue secretory carcinomas, 7 metastatic squamous cell carcinomas, 27 mucoepidermoid carcinomas, 2 oncocytic carcinomas, 5 oncocytomas, 34 pleomorphic adenomas, 4 polymorphous low grade adenocarcinomas, 25 salivary duct carcinomas, and 5 Warthin tumors. Staining for GATA3 was observed in 92/180 (51 %) of salivary gland tumors. GATA3 staining was observed in most of the tumor types, but diffuse immunolabeling was consistently seen in salivary duct carcinoma (25 of 25) and mammary analogue secretory carcinoma (15 of 15)-the two tumor types that most closely resemble breast neoplasia. Background benign salivary gland tissue was also usually weakly positive in both acini and ducts. GATA3 immunostaining is not restricted to tumors of breast and urothelial origin. Rather, it is expressed across many different types of salivary gland neoplasms. As a result, salivary gland origin should be considered in the differential diagnosis of a GATA3-positive carcinoma, particularly in the head and neck. Although GATA3 immunohistochemistry is not helpful in resolving the differential diagnosis between a primary salivary gland neoplasm and metastatic breast
Risk of myeloid neoplasms after solid organ transplantation
Morton, Lindsay M.; Gibson, Todd M.; Clarke, Christina A.; Lynch, Charles F.; Anderson, Lesley A.; Pfeiffer, Ruth; Landgren, Ola; Weisenburger, Dennis D.; Engels, Eric A.
Solid organ transplant recipients have elevated cancer risks, due in part to pharmacologic immunosuppression. However, little is known about risks for hematologic malignancies of myeloid origin. We linked the US Scientific Registry of Transplant Recipients with 15 population-based cancer registries to ascertain cancer occurrence among 207,859 solid organ transplants (1987–2009). Solid organ transplant recipients had significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8–5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2–3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6–3.2; N=36) for chronic myeloid leukemia, and 7.2 (5.4–9.3; N=57) for polycythemia vera. SIRs were highest among younger individuals and varied by time since transplantation and organ type (Poisson regression P<0.05 for all comparisons). Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2–5 years after transplantation, P=0.0163). Overall survival following AML/MDS among transplant recipients was inferior to that of similar patients reported to US cancer registries (log-rank P<0.0001). Our novel finding of increased risks for specific myeloid neoplasms after solid organ transplantation supports a role for immune dysfunction in myeloid neoplasm etiology. The increased risks and inferior survival should heighten clinician awareness of myeloid neoplasms during follow-up of transplant recipients. PMID:24727673
A so-called carcinosarcoma of the gallbladder in a patient with multiple anomalies--a case report.
Eriguchi, N; Aoyagi, S; Hara, M; Hashino, K; Imamura, M; Sato, S; Imamura, I; Kutami, R; Jimi, A
The patient was a 65-year-old woman with a chief complaint of right upper quadrant pain. Under the diagnosis of gallbladder tumor, preduodenal portal vein and absence of the pancreatic tail, cholecystectomy was performed. Intraoperative findings resulted in a diagnosis of gallbladder tumor, absence of the pancreatic tail, presence of preduodenal portal vein, and malrotation of the intestine. Histological examination of the resected specimens showed a so-called carcinosarcoma. Carcinosarcoma of the gallbladder is a rare tumor of the hepatobiliary region. The present case differs from previously reported cases in its presentation with multiple anomalies including the presence of preduodenal portal vein. Many cases of preduodenal portal vein in an association with duodenal stenosis in children have been reported, but reports of cases of preduodenal portal vein in adult patients are rarely seen in the literature.
[Gallbladder emptying evaluation in chronic calcifying pancreatitis, by means of a scintilographic study with Tc-99m DISIDA].
Pedroso, M R; Cunha, R M; Guarita, D R; Buchpieguel, C A; Mott, C B; Laudanna, A T
The aim of this study was to analyze the gallbladder motor function in chronic pancreatitis (CP) patients. Gallbladder emptying was evaluated in 11 patients, without and with addition of pancreatic extract and in ten controls. The results were compared and analyzed statistically. The ejection fraction (EF) of the gallbladder (GB) at 30, 45 and 60 minutes were calculated by using Tc-99m DISIDA scintigraphy. The EF of GB at 60 minutes was significantly higher in the controls when compared to patients, although the results between patients were similar without and with addition of pancreatic extract. The results suggest that the delay in the GB emptying does not depend on the eventual alteration in the intestinal phase of the vesicular stimulation, but it probably results from a mechanic factor, which depends on the chronic pathological process located in the head of the pancreas.
A Strategy for Precise Treatment of Cardiac Malignant Neoplasms
Wang, Wenshuo; Shen, Jinqiang; Tao, Hongyue; Zhao, Yun; Nian, Hui; Wei, Lai; Ling, Xiaoyuan; Yang, Ye; Xia, Limin
The prevalence of cardiac malignant neoplasms in the general population has been shown to be significant higher than what was previously estimated, yet their treatment has remained difficult and effective therapies are lacking. In the current study, we developed a novel thermotherapy in which PEG-functionalized carbon nanotubes were injected into the tumor regions to assist in the targeted delivery of infrared radiation energy with minimal hyperthermic damage to the surrounding normal tissues. In a mouse model of cardiac malignant neoplasms, the injected carbon nanotubes could rapidly induce coagulative necrosis of tumor tissues when exposed to infrared irradiation. In accordance, the treatment was also found to result in a restoration of heart functions and a concomitant increase of survival rate in mice. Taken together, our carbon nanotube-based thermotherapy successfully addressed the difficulty facing conventional laser ablation methods with regard to off-target thermal injury, and could pave the way for the development of more effective therapies against cardiac malignant neoplasms. PMID:28393926
Tryptophan autofluorescence imaging of neoplasms of the human colon
NASA Astrophysics Data System (ADS)
Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs
Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.
Clinical parameters predictive of malignancy of thyroid follicular neoplasms
Davis, N.L.; Gordon, M.; Germann, E.; Robins, R.E.; McGregor, G.I. )
Needle aspiration biopsy is commonly employed in the evaluation of thyroid nodules. Unfortunately, the cytologic finding of a 'follicular neoplasm' does not distinguish between a thyroid adenoma and a follicular cancer. The purpose of this study was to identify clinical parameters that characterize patients with an increased risk of having a thyroid follicular cancer who preoperatively have a 'follicular neoplasm' identified by needle aspiration biopsy. A total of 395 patients initially treated at Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1965 and 1985 were identified and their data were entered into a computer database. Patients with thyroid adenomas were compared to patients with follicular cancer using the chi-square test and Student's t-test. Statistically significant parameters that distinguished patients at risk of having a thyroid cancer (p less than 0.05) included age greater than 50 years, nodule size greater than 3 cm, and a history of neck irradiation. Sex, family history of goiter or neoplasm, alcohol and tobacco use, and use of exogenous estrogen were not significant parameters. Patients can be identified preoperatively to be at an increased risk of having a follicular cancer and accordingly appropriate surgical resection can be planned.
Occult gallbladder carcinoma after laparoscopic cholecystectomy: a report of four cases.
Yokomuro, Shigeki; Arima, Yasuo; Mizuguchi, Yoshiaki; Shimizu, Tetsuya; Kawahigashi, Yutaka; Kannda, Tomohiro; Arai, Masao; Tajiri, Takashi
Eighty-four patients underwent laparoscopic cholecystectomy (LC) from January through August 2006. Of these patients, 4 (4.7%) were found to have occult gallbladder carcinoma (GC) either during or after the procedure. Two of the patients were women and 2 were men. The mean age was 75.0 years. One patient had mucosal tumors, 2 had subserosal tumors, and 1 had a serosal lesion. One of the 2 patients with subserosal tumors underwent radical surgery. In a previous study, 0.83% (10 of 1,195) of patients who had undergone LC were found to have occult GC, either during of after the procedure. The prevalence of gallbladder carcinoma has recently been increasing. GC has been reported in 0.3% to 1.5% of patients who have undergone cholecystectomy. Since the introduction of laparoscopic surgery, the number of cholecystectomies being performed has increased, which may explain why occult GC seems to be occurring more frequently. The prognosis for GC is poor, and surgical resection is the only potentially curative treatment. However, GC is difficult to diagnose at an early stage and difficult to recognize even in the advanced stages. Fifteen percent to 30% of patients show no preoperative or intraoperative evidence of malignancy. Occult GC is also increasing. Because flat infiltrating GC and GC with cholecystitis and numerous stones are difficult to diagnose preoperatively, we recommend taking frozen sections from patients who are of advanced age (older than 70 years), have a long history of stones, or have a thickened gallbladder wall.
Factors affecting morphogenesis of rabbit gallbladder epithelial cells cultured in collagen gels.
Mori, M; Miyazaki, K
Although peptide growth factors play an important role in the morphogenesis of gallbladder, little is known about how they effect the morphogenesis of gallbladder epithelial cells. Rabbit gallbladder epithelial cells (RGEC) were isolated and cultured in monolayer or collagen gels. Epidermal growth factor (EGF), hepatocyte growth factor (HGF), epimorphin, transforming growth factor-beta 1 (TGF-beta 1), and fibroblast-conditioned medium (FCM) were added to the cultured cells to clarify the effects of these peptides and FCM on morphogenesis of RGEC. RGEC suspended in collagen gels form spherical cysts with morphologic polarity. EGF, HGF, epimorphin, and FCM promoted cyst maturation by accelerating the proliferation and aggregation of clear, polarized vesicles. In contrast, TGF-beta 1 markedly inhibited DNA synthesis in both monolayer and collagen gel cultures and promoted formation of branching structures in collagen gels. Furthermore, in the presence of EGF, TGF-beta 1 induced a drastic change in morphogenesis, with the formation of branching networks that showed cell-cell contact only at sites where branches touched. RGEC-forming multicellular cysts did not express vimentin but expressed significant amounts of cytokeratin and regained junctional complexes. In contrast, TGF-beta 1-treated cells strongly expressed vimentin along with branching structures and showed decreases in cytokeratin expression and junctional complexes. Thus, TGF-beta 1 induces a mesenchyme-like cell shape accompanied by cytoskeletal molecular changes, with loss of both epithelial polarization and junctional complexes. These results suggest that the morphogenetic program of RGEC is likely to be determined by the interaction of these peptides and the timing of their presence.
Expression of S-100 protein in renal cell neoplasms.
Lin, Fan; Yang, Wannian; Betten, Mark; Teh, Bin Tean; Yang, Ximing J
Polyclonal antibody to S-100 protein has been routinely applied for initial screening of various types of tumors, including, melanocytic tumors and neurogenic tumors. S-100 protein has been shown to have a broad distribution in human tissues, including renal tubules. The potential utility of S-100 protein in renal cell neoplasms has not been extensively investigated. Using an EnVision-Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the diagnostic value of S-100 protein on tissue microarray sections from 175 cases of renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using the same antibody (anti-S-100 protein) was performed on 10 cases of renal cell neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and 13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100 protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%) of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of 30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in oncocytomas compared with ChRCCs was confirmed by the data of Western blot and cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3% (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (-)/S-100 protein (+). These data indicate that caution should be taken in interpreting an unknown primary with S-100 positivity and cytokeratin negativity. In addition, it
Normal Gallbladder Ejection Fraction Occurring Unexpectedly Obviates Need for Sincalide Stimulation.
Hadi, Samir; Tulchinsky, Mark
A 25-year-old man was referred for chronic right upper quadrant abdominal pain for hepatobiliary scintigraphy to evaluate the gallbladder (GB) function. An unexpected GB contraction with ejection fraction (EF) of 90% was observed during the first hour of baseline imaging. Subsequent stimulation with sincalide produced GB EF of 99%. A similar case previously reported also showed normal unexpected GB EF that predicted similar post-sincalide GB EF. These examples support what should be evident: A normal unexpected GB EF is a sufficient evidence for a normal GB function and should obviate need for sincalide stimulation.
Case Report of Ectopic Liver on Gallbladder Serosa with a Brief Review of the Literature
Farooq, Mohammad S.; Soni, Utsav; Kalabin, Aleksandr; Rajabalan, Ajai S.; Ahmed, Leaque
This case describes an intraoperative incidental finding and surgical removal of ectopic liver tissue attached to the gallbladder during a standard laparoscopic cholecystectomy for acute cholecystitis. These anomalies are rare, with interesting associations and possible clinically relevant complications. The details of the case, along with a brief literature review of embryology, common ectopic sites, and associations/complications, are presented in this paper. Since laparoscopic cholecystectomy is a very common procedure, it is important to increase vigilance of ectopic liver tissues during surgeries to minimize complications and provide optimal management. PMID:27803835
Renal cell carcinoma metastatic to gallbladder: a survival advantage to simultaneous nephrectomy and cholecystectomy.
Hellenthal, Nicholas J; Stewart, Gregory S; Cambio, Angelo J; Delair, Sean M
Renal cell carcinoma is a relatively uncommon cancer. Patients presenting with a renal adenocarcinoma are often found to have evidence of metastatic disease at the time of diagnosis. Herein, we describe the case of a 39-year-old male with renal cell carcinoma and a synchronous metastatic focus to the gallbladder. The patient underwent a successful simultaneous nephrectomy and cholecystectomy and is doing well 30 months after surgery without evidence of disease recurrence. A thorough metastatic work-up along with aggressive surgical intervention in patients with renal cell carcinoma and unusual metastatic foci can provide a long-term favorable outcome.
18F-FDG PET/CT Imaging of Gallbladder Adenocarcinoma - A Pictorial Review
Awan, Omer; Khan, Salman A
Gallbladder adenocarcinoma is an uncommon and serious disease. The primary disease grows rapidly with local invasion into the liver and with distant spread to lymph nodes. It is often detected late, due to which management can be challenging. Despite routine use of computed tomography (CT) and ultrasonography (US) for detection, magnetic resonance imaging (MRI) is often considered for a detailed assessment of the anatomic behavior of these tumors. We share three cases where 18-FDG PET/CT played a role in management thereof. PMID:26430572
Simultaneous xanthogranulomatous cholecystitis and gallbladder cancer in a patient with a large abdominal aortic aneurysm.
Al-Abed, Yahya; Elsherif, Mohammed; Firth, John; Borgstein, Rudi; Myint, Fiona
There have been reports of the coexistence of abdominal aortic aneurysm (AAA) with intra-abdominal malignancy including gastric, colonic, pancreatic, and renal. We herein report a case of a previously undiagnosed AAA and a presenting complaint consistent with acute cholecystitis. Following cholecystectomy, this was noted to be a rare form of chronic cholecystitis: xanthogranulomatous cholecystitis. There is a known possible association of this uncommon condition with gallbladder cancer. The management of concomitant pathologies can present a real challenge to the multidisciplinary team, especially with large aneurysms.
Classification of feline intraocular neoplasms based on morphology, histochemical staining, and immunohistochemical labeling.
Grahn, Bruce H; Peiffer, Robert L; Cullen, Cheryl L; Haines, Deborah M
The objectives of this study were to evaluate morphologic, histochemical, and immunohistochemical characteristics of well-differentiated and anaplastic intraocular neoplasms of cats, and to develop a diagnostic algorithm for, and investigate the association of ruptured lenses with these neoplasms. Seventy-five feline globes with intraocular neoplasms were stained with hematoxylin and eosin and examined by light microscopy. Morphologic diagnoses included 33 intraocular sarcomas, 17 diffuse iris melanomas, 15 lymphosarcomas, three ciliary adenomas, one metastatic carcinoma, and six undifferentiated intraocular neoplasms. Sections of these globes were then stained with periodic acid Schiff (PAS), and immunohistochemical (IHC) labels for various cellular markers. Histochemical staining and IHC labeling confirmed cellular differentiation in 73/75 neoplasms but was discordant with morphologic diagnoses in 8/75. These included four neoplasms morphologically diagnosed as lymphosarcomas but which expressed differentiation antigens consistent with melanoma (n = 3) or ciliary adenocarcinoma (n = 1), and four tumors morphologically diagnosed as intraocular sarcomas that expressed differentiation antigens for melanoma (n = 2), metastatic carcinoma (n = 1), or remained undifferentiated (n = 1). Immunohistochemical labeling suggested a diagnosis in 5/6 morphologically undifferentiated neoplasms including one intraocular sarcoma, two diffuse iridal melanomas, and two ciliary adenocarcinomas. Based upon morphologic, histochemical, and IHC characterization, ruptured lens capsules were detected in 28/30 intraocular sarcomas, 3/24 diffuse iris melanomas and 1/11 lymphosarcomas, but not in ciliary epithelial neoplasms, metastatic carcinomas, or undifferentiated intraocular neoplasms. An algorithm is provided that facilitates stain and IHC label selection for differentiating anaplastic intraocular feline neoplasms.
Morphological and immunohistochemical characterization of spontaneous thyroid gland neoplasms in guinea pigs (Cavia porcellus).
Gibbons, P M; Garner, M M; Kiupel, M
Reports of thyroid gland neoplasms in guinea pigs (Cavia porcellus) are rare, but thyroid tumors are among the most common neoplasms seen in cases submitted to Northwest ZooPath. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms and lists the concurrent conditions found in guinea pig cases submitted to Northwest ZooPath during 1998 to 2008. Of 526 guinea pig case submissions, 19 had thyroid neoplasms. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Neoplasms were removed as an excisional biopsy from 7 guinea pigs, and 3 of these animals died within a few days after surgery. Radiographic mineral density was detected in 2 masses. Five of the neoplasms were reported as cystic; 5 were black or a dark color. Histologically, the neoplasms were classified as macrofollicular thyroid adenoma (8), thyroid cystadenoma (1), papillary thyroid adenoma (3), follicular thyroid carcinoma (5), follicular-compact thyroid carcinoma (1), and small-cell thyroid carcinoma (1). Osseous metaplasia was present in 8 neoplasms, and myeloid hyperplasia was present in 1 neoplasm. All 19 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin but negative for parathyroid hormone and calcitonin. Numerous concurrent diseases, including hepatopathies, cardiomyopathies, and nephropathies, were present and considered to be the cause of death in many cases. Research is needed to determine the appropriate modalities for antemortem diagnosis and treatment and whether thyroid disease plays a role in the pathogenesis of chronic degenerative diseases in guinea pigs.
Acinar neoplasms of the pancreas-A summary of 25 years of research.
Klimstra, David S; Adsay, Volkan
Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related. Cystic and extrapancreatic forms have been described. These neoplasms share molecular alterations that are distinct from the more common ductal and neuroendocrine neoplasms of the pancreas. Although there is a broad range of genetic findings, a number of potential therapeutic targets have emerged. This review explores the clinical and pathologic features of pancreatic acinar neoplasms along with their more common molecular phenotypes. The differential diagnosis with other pancreatic neoplasms is explored as well.
Frequency and Histopathology by Site, Major Pathologies, Symptoms and Signs of Salivary Gland Neoplasms.
Bradley, Patrick J
The frequency distribution of salivary gland neoplasms (SGNs) is, in decreasing order, parotid neoplasms, submandibular gland neoplasms, minor SGNs, and sublingual gland neoplasms. The larger the salivary gland (e.g. parotid), the more likely a neoplasm is benign, and the smaller the gland (e.g. minor salivary gland), the more likely the neoplasm is malignant. The majority of SGNs, benign and/or malignant, irrespective of site, present as a painless swelling or mass. Definitive symptoms and signs of salivary gland malignancy are the presence of named nerve palsy in anatomical proximity to the gland and/or the presence of cervical lymphadenopathy. All discrete major salivary gland masses and non-ulcerated submucosal masses presenting in the head and neck region, irrespective of age, should be investigated, with the aim of excluding an SGN.
The relationship of the sphincter of Oddi to the stomach, duodenum and gall-bladder
Wyatt, A. P.
Flow through the sphincter of Oddi was studied by a constant-pressure perfusion apparatus, and by using a constant rate of infusion and measuring pressure changes just proximal to the sphincter. Pressure changes from balloons placed in the gastric antrum and duodenum were recorded. Despite considerable variation in activity and behaviour, the following conclusions were reached. 1. The sphincter of Oddi appears to be partially autonomous but is readily affected by changes in duodenal tone. 2. Reflex inhibition of the sphincter of Oddi is seen on electrical and mechanical stimulation of the gall-bladder but not with passive pressure changes within the gall-bladder. 3. This reflex is relayed through the coeliac ganglion. 4. There is a definite relationship between gastric antral activity and flow through the sphincter of Oddi. This is more obvious when food is present in the stomach. 5. Mechanical or electrical stimulation of the stomach, duodenum, or upper small bowel influences the tone of the sphincter of Oddi. PMID:6065875
[Surgical treatment of particularly complicated forms of gall-bladder and anhepatic bile-duct diseases].
Archvadze, B K; Tedoradze, V O; Tsekhelashvili, L O; Berishvili, K L
The authors offer analysis of surgical treatment methods of patients suffering from complicated forms of gall-bladder and anhepatic bile-excreting ducts' diseases. In elaborating tactics for treatment of the above-mentioned pathology the presently existing technical and tactical approaches are considered and the most acceptable for receiving favourable results are chosen. In implementing the operation the authors gave utmost attention to the choice of the method of bile-duct drainage depending on the severity of the disease, the age and the concomitant diseases. Taking into consideration application of the most approved and effective methods of treatment of complicated forms of gall-bladder and bile-duct diseases, 191 patients were operated within the period of 1990-2008 years. The operation cholecystectomy together with drainage of the choledochus was carried out in 64 cases, choledochoduodenostomy - in 54 cases, choledochojejunostomy - in 59 cases, reconstruction of the choledochus over a T-tube Kerr's drainage - in 8 cases. The portion of the gall-duct retained after the first operation was removed to 3 patients. There were 18 (9,4%) cases of complications in post-operation period, 8 patients died, lethality was 4,2%.
Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor.
Zou, Hao; Liu, Yunxia; Wei, Dong; Wang, Tao; Wang, Kun; Huang, Songquan; Liu, Lixin; Li, Yuehua; Ge, Jiayun; Li, Xiao; Zhu, Hong; Wang, Lianmin; Zhao, Songling; Zhang, Xiaowen; Wang, Lin
Emerging evidence has shown that leptin, an adipocyte-derived cytokine that is closely associated with obesity, play a significant role in carcinogenesis and tumorigenesis. However, its impact on gallbladder cancer (GBC) remains unclear. In this study, we firstly found that leptin and its functional receptor OB-Rb were significantly co-expressed in human GBC tissues and cell lines, the content of which were higher than those in normal human gallbladder tissues. Treatment with leptin promoted the proliferation, migration and invasion of GBC cells, which were attenuated by OB-Rb shRNA. Blocking in the G2/M period of cell cycle, increasing of MMP3 and MMP9, increasing of VEGF-C/D, activation of SOCS3/JAK2/p-STAT3 pathway was demonstrated after treatment with leptin. All of these positive responses were attenuated by OB-Rb receptor shRNA. Taken together, our findings suggest that leptin promoted the proliferation, migration and invasion of GBC cells by increasing OB-Rb expression through the SOCS3/JAK2/p-STAT3 signal pathway. Targeting the leptin/OB-Rb axis could be an attractive therapeutic strategy for treatment of GBC.
Gallbladder dysfunction enhances physical density but not biochemical metastability of biliary vesicles.
Sunami, Y; Tazuma, S; Kajiyama, G
The gallbladder role in cholesterol gallstone pathogenesis occurs through modulation of bile cholesterol metastability. The present study characterized the effects of concentrating bile on cholesterol crystallization through vesicle transformation, crystal habits, and potentiation of effector substances. Supersaturated model biles with total lipid concentrations of 12, 9, 6, and 3 g/dl were prepared with identical molar ratios (taurocholate-egg yolk phosphatidylcholine-cholesterol: 71:18:11). Bile metastability was assessed spectrophotometrically, and morphology of vesicle and crystal was sequentially scanned by video-enhanced differential contrast microscopy. The effects of replacing 30% of egg yolk phosphatidylcholine with soy bean phosphatidylcholine, 30% of taurocholate with taurodeoxycholate or tauroursodeoxycholate, and addition of concanavalin A-binding glycoprotein on each model bile were examined. By lowering total lipid concentration, cholesterol crystallization was retarded with less fusion and aggregation of vesicles. The effects of substances promoting cholesterol crystallization were enhanced with lesser bile. By replacing 30% of taurocholate with tauroursodeoxycholate, cholesterol crystallization was markedly inhibited in all concentrations, forming stable liquid-crystals. Impaired water absorption by the gallbladder may stabilize vesicles and inhibit rapid cholesterol crystallization, but the potential of cholesterol crystallization effector substances must be modified to alter bile cholesterol metastability.
To Resect or Not to Resect Extrahepatic Bile Duct in Gallbladder Cancer?
Gavriilidis, Paschalis; Askari, Alan; Azoulay, Daniel
The indications for and limitations of extrahepatic bile duct resection (EHBDR) in the context of gallbladder (GB) cancer are unclear. The purpose of this review was to examine the current literature to determine the impact of EHBDR on loco-regional recurrence and survival in GB cancer. The EMBASE and Medline databases were searched up to February 2016 using the terms: extrahepatic bile duct resection and gallbladder cancer. Studies published in the last 20 years were eligible for inclusion. Given the heterogeneity of the population and the study methodologies employed, qualitative data synthesis in the form of meta-analysis was deemed implausible. Twenty-four studies fulfilled the inclusion criteria. The selected studies include 6,722 (55%) EHBDRs in a total of 12,251 GB cancer operations. The 25 studies were categorized into seven groups: 1) cancer survival all stages; 2) hepatoduodenal ligament invasion; 3) outcome in EHBDR and EHBDNR; 4) pT1b tumors; 5) pT2 tumors; 6) pT3/T4 tumors; and 7) incidental GB cancer. Radical cholecystectomy with EHBDR should be used as a standard operation for tumors involving the neck or the cystic duct of the GB (either macroscopically or microscopically). In all other cases, operative strategy should be individualized to the patient. PMID:28090223
Inhibition of mTOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition.
Zong, Huajie; Yin, Baobing; Zhou, Huading; Cai, Duan; Ma, Baojin; Xiang, Yang
Gallbladder cancer (GBC) is an aggressive disease in which epithelial-mesenchymal transition (EMT) plays a critical role. Whether inhibition of mTOR effects via EMT reversal in GBC remains unclear. Using genetic and pharmacologic inhibitions of mTOR, we investigated the changes of EMT levels in GBC cells. Expressions of EMT related genes were also studied. Migration and invasion assays were carried out and in vivo tumour metastasis mouse models were established. Circulating tumour DNA was quantified. We used EMT index (ratio of Vimentin/Ecadherin expression) to profile EMT levels. We found that inhibition of mTOR using shRNAs and rapamycin inhibited EMT in GBC-SD gallbladder cancer cells. Inhibition of mTOR inhibited EMT in GBC-SD cells in TGF-β-dependent manner, which was contributed majorly by mTORC2 inhibition. Rapamycin decreased invasiveness and migration of GBC-SD cells in vitro and in vivo. We have in the current study shown that rapamycin diminishes the ability of invasion and migration of GBC via inhibition of TGF-β-dependent EMT. Our findings contribute to the understanding of the carcinogenesis of GBC.
To Resect or Not to Resect Extrahepatic Bile Duct in Gallbladder Cancer?
Gavriilidis, Paschalis; Askari, Alan; Azoulay, Daniel
The indications for and limitations of extrahepatic bile duct resection (EHBDR) in the context of gallbladder (GB) cancer are unclear. The purpose of this review was to examine the current literature to determine the impact of EHBDR on loco-regional recurrence and survival in GB cancer. The EMBASE and Medline databases were searched up to February 2016 using the terms: extrahepatic bile duct resection and gallbladder cancer. Studies published in the last 20 years were eligible for inclusion. Given the heterogeneity of the population and the study methodologies employed, qualitative data synthesis in the form of meta-analysis was deemed implausible. Twenty-four studies fulfilled the inclusion criteria. The selected studies include 6,722 (55%) EHBDRs in a total of 12,251 GB cancer operations. The 25 studies were categorized into seven groups: 1) cancer survival all stages; 2) hepatoduodenal ligament invasion; 3) outcome in EHBDR and EHBDNR; 4) pT1b tumors; 5) pT2 tumors; 6) pT3/T4 tumors; and 7) incidental GB cancer. Radical cholecystectomy with EHBDR should be used as a standard operation for tumors involving the neck or the cystic duct of the GB (either macroscopically or microscopically). In all other cases, operative strategy should be individualized to the patient.
Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and gallbladder carcinoma.
Xie, Fang; Xu, Xiaoping; Xu, Angao; Liu, Cuiping; Liang, Fenfen; Xue, Minmin; Bai, Lan
Sonic hedgehog (Shh) signaling has been extensively studied and is implicated in various inflammatory diseases and malignant tumors. We summarized the clinicopathological features and performed immunohistochemistry assays to examine expression of Shh signaling proteins in 10 normal mucosa, 32 gallbladder carcinoma (GBC), and 95 chronic cholecystitis (CC) specimens. The CC specimens were classified into three groups according to degree of inflammation. Compared with normal mucosa, CC, and GBC specimens exhibited increased expression of Shh. The immunoreactive score of Shh in the GBC group was higher than that in the mild to moderate CC groups but lower than that in the severe CC group (P < .05). Expression of Patched (Ptch) and Gli1 gradually increased from non-malignant cholecystitis to malignant tumors. Compared with CC specimens, GBC specimens showed higher cytoplasmic and membranous expression for Ptch (P < .05). Gli1 staining showed cytoplasmic expression of Gli1 in both CC (60% for mild, 77% for moderate, and 84% for severe) and GBC specimens (97%). Nuclear expression of Gli1 was detected in 16% of severe CC specimens with moderate to poor atypical hyperplasia, and in 62.5% of GBC specimens. Shh expression strongly correlated with expression of Ptch and Gli1. Furthermore, patients with strongly positive Gli1 staining had significantly lower survival rates than those with weakly positive staining. Our data indicate that the Shh signaling pathway is aberrantly activated in CC and GBC, and altered Shh signaling may be involved in the course of development from CC to gallbladder carcinogenesis.
Gallbladder perforation: a rare complication of postoperative chemotherapy of gastric cancer.
Sun, Yanlai; Song, Wentao; Hou, Qingsheng; Li, Jianning; Guo, Hongliang
A middle-aged man presented 1 day after being discharged from hospital with completing the first course of postoperative chemotherapy. He suffered a sudden persistent high fever and chills. It was noted that he had a history of a total gastrectomy (with D2 lymphadenectomy) 1 month ago. His admission bloods revealed total bilirubin was 142.2 umol/L, indirect bilirubin of 107.6 umol/L and white cell count of 20.05×10(9)/L. A color doppler ultrasound scan confirmed fluid and gas around liver and hilus lienis while the gallbladder cannot be detected. During Computed Tomography (CT) guided puncture positioning technology and setting a three-channel tube, about 400 ml of foul smell hazel turbid liquid was drained out. He was diagnosed as gallbladder perforation and he was underwent conservative treatment consist of drainage, banning diet, total parenteral nutrition and intravenous antibiotics. Then he recovered well within the subsequent 10 days and was discharged.
Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α
Gao, Hui; Xie, Jing; Peng, Jianjun; Han, Yantao; Jiang, Qixiao; Han, Mei; Wang, Chunbo
Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment. - Highlights: • Hispidulin inhibits proliferation of gallbladder cancer cells by targeting HIF-1α. • Hispidulin regulates HIF-1α via activating AMPK signaling. • Hispidulin sensitized the GBC cells to chemotherapeutics by down-regulating P-gp.
[Evaluation of enterogastric reflux in relation to functional status of the gallbladder].
Artiko, V; Chebib, H; Petrović, N; Davidović, B; Vlajković, M; Petrović, M; Milićević, M; Ussov, W Y; Obradović, V
The aim of the study was estimation of the relation between the gallbladder (GB) motility function and the presence and quantity of enterogastric reflux (EGR). We investigated 172 patients with: physiological GB function (filling and emptying)(FGB), impaired GB function (prolonged filling and ejection fraction < 45%) and afunctional gallbladder (AGB)(without visualization). The study was performed during 90 min (1 f/min) after i.v. application of 185 MB 99mTc-dietil IDA. After 30 min. test meal was given while at the end stomach was marked. According to the parameters from time activity curves over stomach and hepatobiliary system, the index of ERG was calculated, while GB filling and ejection fraction were estimated from the GB time/activity curve. We can conclude that EGR occurs more frequently in the patients with afunctional GB in comparison to those with functional and decreased motor function. Also, EGR quantity is in correlation with the impairment of the GB function.
Primary Pure Squamous Cell Carcinoma of the Gallbladder Locally Invading the Liver, Duodenum, and Stomach: A Case Report and Literature Review
Alpuerto, Aldrin C.; Mora, Maximo E.
Primary pure squamous cell carcinoma (SCC) of the gallbladder is an exceptionally rare type of tumor that comprises only 1% of all gallbladder cancer. SCC of the gallbladder portends a worse prognosis than the more common adenocarcinoma variant because of its aggressive invasion to local structures and because it is often diagnosed at an advanced stage. Owing to its rarity, diagnosis and management can be challenging. Herein, we present the case of a 75-year-old female complaining of abdominal pain, nausea, and vomiting. Computed tomography and ultrasonography results of the abdomen were consistent with acute cholecystitis and cholelithiasis. Histologic evaluation of the resected mass revealed a malignant tumor with prominent keratinization, confirming the diagnosis of an invasive primary pure SCC of the gallbladder. Microscopic examination showed direct infiltration to the liver, duodenum, and stomach. This case report describes the hospital course of a patient with SCC of the gallbladder and suggests that gallbladder cancer should be considered as part of the differential diagnosis in elderly patients presenting with acute cholecystitis. In addition, this article will review existing literature to examine the utility of different diagnostic techniques and treatment modalities available in the management of gallbladder cancer. PMID:28251014
Dieulafoy lesion of the gallbladder presenting with bleeding and a pseudo-mirizzi syndrome: A case report and review of the literature
Stanes, Aaron; Mackay, Sean
Introduction Gastrointestinal bleeding can have significant morbidity and mortality. Pathological processes that cause it are diverse, and timely investigation and management are vital. Dieulafoy lesions are a rare cause of gastrointestinal bleeding and here we describe a case of a gallbladder dieulafoy lesion causing gastrointestinal bleeding. Presentation of case Recently discharged from hospital following an open anterior resection and loop ileostomy for diverticular disease, an 84-year-old female re-presented with lower abdominal pain associated with jaundice and lymphocytosis. Imaging demonstrated two possible rectal stump collections (treated with antibiotics), and heterogeneous material in the gallbladder. The patient deteriorated, developing melena, coffee ground vomitus and right upper quadrant pain. Investigation sourced the bleeding to the gallbladder that resolved following cholecystectomy, and histopathology was consistent with a dieulafoy lesion. The patient made a full recovery. Discussion Dieulafoy lesions have rarely been reported in the gallbladder, and as such can be an occult source of massive gastrointestinal bleeding. It should be considered where gastrointestinal bleeding accompanies jaundice and abdominal pain. Conclusion This case highlights that dieulafoy lesions can occur in the gallbladder. Massive gastrointestinal bleeding can occur within the gallbladder, and a gallbladder dieulafoy lesion should be considered as a potential cause of such, especially when a source has not been identified on endoscopy. It also demonstrates the effectiveness of cholecystectomy as a definitive management strategy. PMID:26878358
Radiation-induced intracranial neoplasms. A report of three possible cases
Anderson, J.R.; Treip, C.S.
The pathologic findings are described in three patients who developed second intracranial neoplasms after irradiation for central nervous system malignancy. The second neoplasms were an astrocytoma, an ependymoma, and multiple meningiomas. All were histologically different from the first neoplasms and appeared in the field of irradiation between 3 and 15 years later. It is suggested that therapeutic irradiation was a causative factor in the development of these tumors.
Radiation-induced intracranial neoplasms. A report of three possible cases.
Anderson, J R; Treip, C S
The pathologic findings are described in three patients who developed second intracranial neoplasms after irradiation for central nervous system malignancy. The second neoplasms were an astrocytoma, an ependymoma, and multiple meningiomas. All were histologically different from the first neoplasms and appeared in the field of irradiation between 3 and 15 years later. It is suggested that therapeutic irradiation was a causative factor in the development of these tumors.
Update on surgical treatment of pancreatic neuroendocrine neoplasms
D'Haese, Jan G; Tosolini, Chiara; Ceyhan, Güralp O; Kong, Bo; Esposito, Irene; Michalski, Christoph W; Kleeff, Jörg
Pancreatic neuroendocrine neoplasms (PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential (neurendocrine tumors PNETs) or overt (neuroendocrine carcinomas PNECs) malignant, but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimally-invasive approaches which should be tailored to the individual patient. Generally, surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs, indications for tumor resection are much wider than for pancreatic adenocarcinoma, in many cases due to the relatively benign tumor biology. Thus, patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands, even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However, poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly single-center series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable, ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review, we summarize recent advances in the surgical treatment of PNENs. PMID:25320524
The myeloproliferative neoplasms, unclassifiable: clinical and pathological considerations.
Gianelli, Umberto; Cattaneo, Daniele; Bossi, Anna; Cortinovis, Ivan; Boiocchi, Leonardo; Liu, Yen-Chun; Augello, Claudia; Bonometti, Arturo; Fiori, Stefano; Orofino, Nicola; Guidotti, Francesca; Orazi, Attilio; Iurlo, Alessandra
In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects. Interestingly, more than half of the cases displayed severe bone marrow fibrosis (59%). Median values of hemoglobin level and white blood cells count were all within the normal range; in contrast, median platelets count and lactate dehydrogenase were increased. Little less than half of the patients (44%) showed splenomegaly. JAK2V617F mutation was detected in 72% of all patients. Among the JAK2-negative cases, MPLW515L mutation was found in 17% and CALR mutations in 67% of the investigated cases, respectively. Finally, by multiple correspondence analysis of the morphological profiles, we found that all but four of the cases could be grouped in three morphological clusters with some features similar to those of the classic BCR-ABL1-negative myeloproliferative neoplasms. Analysis of the clinical parameters in these three clusters revealed discrepancies with the morphological profile in about 55% of the patients. In conclusion, we found that the category of myeloproliferative neoplasm, unclassifiable is heterogeneous but identification of different subgroups is possible and should be recommended for a better management of these patients.
Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report
Bezpalko, Kseniya; Mohamed, Mohamed A.; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth
Introduction At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. Presentation of case A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. Discussion The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Conclusion Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. PMID:26275738
Novel Small Molecule Agonist of TGR5 Possesses Anti-Diabetic Effects but Causes Gallbladder Filling in Mice.
Briere, Daniel A; Ruan, Xiaoping; Cheng, Christine C; Siesky, Angela M; Fitch, Thomas E; Dominguez, Carmen; Sanfeliciano, Sonia Gutierrez; Montero, Carlos; Suen, Chen S; Xu, Yanping; Coskun, Tamer; Michael, M Dodson
Activation of TGR5 via bile acids or bile acid analogs leads to the release of glucagon-like peptide-1 (GLP-1) from intestine, increases energy expenditure in brown adipose tissue, and increases gallbladder filling with bile. Here, we present compound 18, a non-bile acid agonist of TGR5 that demonstrates robust GLP-1 secretion in a mouse enteroendocrine cell line yet weak GLP-1 secretion in a human enteroendocrine cell line. Acute administration of compound 18 to mice increased GLP-1 and peptide YY (PYY) secretion, leading to a lowering of the glucose excursion in an oral glucose tolerance test (OGTT), while chronic administration led to weight loss. In addition, compound 18 showed a dose-dependent increase in gallbladder filling. Lastly, compound 18 failed to show similar pharmacological effects on GLP-1, PYY, and gallbladder filling in Tgr5 knockout mice. Together, these results demonstrate that compound 18 is a mouse-selective TGR5 agonist that induces GLP-1 and PYY secretion, and lowers the glucose excursion in an OGTT, but only at doses that simultaneously induce gallbladder filling. Overall, these data highlight the benefits and potential risks of using TGR5 agonists to treat diabetes and metabolic diseases.
Trend analysis and survival of primary gallbladder cancer in the United States: a 1973-2009 population-based study.
Rahman, Rubayat; Simoes, Eduardo J; Schmaltz, Chester; Jackson, Christian S; Ibdah, Jamal A
Primary gallbladder cancer is an aggressive and uncommon cancer with poor outcomes. Our study examines epidemiology, trend, and survival of gallbladder cancer in the United States from 1973 to 2009. We utilized the Surveillance Epidemiology and End Results database (SEER). Frequency and rate analyses on demographics, stage, and survival were compared among non-Hispanic whites, Hispanics, African American, and Asian/Pacific Islanders. A total of 18,124 cases were reported in SEER from 1973 to 2009 comprising 1.4% of all reported gastrointestinal cancers. Gallbladder cancer was more common in females than males (71 vs. 29%, respectively). The age-adjusted incidence rate was 1.4 per 100,000, significantly higher in females than males (1.7 vs. 1.0). Trend analysis showed that the incidence rate has been decreasing over the last three decades for males. However, among females, the incidence rate had decreased from 1973 to mid-90s but has remained stable since then. Trend analysis for stage at diagnosis showed that the proportion of late-stage cases has been increasing significantly since 2001 after a decreasing pattern since 1973. Survival has improved considerably over time, and survival is better in females than males and in Asian/Pacific Islanders than other racial groups. The highest survival was in patients who received both surgery and radiation. Trend analysis revealed a recent increase of the incidence of late-stage gallbladder cancer. Highest survival was associated with receiving both surgery and radiation.
Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters.
Nakano, K; Todo, T; Chijiiwa, K; Tanaka, M
Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.
The evaluation of gallbladder function by quantitative radionuclide cholescintigraphy before and after ESWL for gallstones: preliminary report.
Kao, C H; Wang, S J; Liu, T J; Wu, C C
We assessed changes of gallbladder function including concentration and contraction in patients with gallstones after extracorporeal shockwave lithotripsy (ESWL). The abilities of concentration and contraction were expressed as filling fraction (FF) at 90 min and ejection fraction (EF) at 30 min after a fatty diet by Tc-99m DISIDA cholescintigraphy. A total of 12 patients who had symptomatic gallstones without cholecystitis were included in our study. ESWL failed in three cases: FF decreased in two of three cases and increased in one of three cases, whereas EF decreased in two of three cases and increased in one of three cases. In another nine cases, ESWL was successful and the gallstones were fragmented. One month after ESWL, in three of these nine cases, the gallstones had completely disappeared. In the three cases at 1 month after ESWL, FF decreased in two of three cases and increased in one of three cases, whereas EF decreased in one of three cases and increased in two of three cases. In the remaining six cases after ESWL, there were still some residual stone fragments in the gallbladder. In these six cases after 6 months, no fragments were found in the gallbladders, the third Tc-99m DISIDA cholescintigraphy was performed. In these six cases, the changes of FF and EF, before ESWL, 1 month after ESWL, and 6 months after ESWL, were irregular and fluctuant. However, no significant improvement of gallbladder function was demonstrated even when ESWL was successful.(ABSTRACT TRUNCATED AT 250 WORDS)
Gallbladder emptying in diabetic patients and control subjects assessed by real-time ultrasonography and cholescintigraphy: a methodological comparison.
Krönert, K; Götz, V; Reuland, P; Luft, D; Eggstein, M
Gallbladder motor function was studied in nine diabetic patients and nine control subjects matched for sex, age, and weight. None of the subjects had gallstones. Two different techniques were employed: real-time ultrasonography and cholescintigraphy using 99mTc-HIDA as imaging agent. Gallbladder volumes were determined sonographically by using three dimensions: length, lateral, and anterior-posterior diameters. Gallbladder emptying was stimulated by a standard test drink (Biloptin). Ejection fraction was computed and the results obtained by both techniques were compared. Fasting and residual gallbladder volumes after contraction were significantly larger in the diabetic patients than in the control subjects (15.9 +/- 7.6 cm3 vs. 2.3 +/- 1.3 cm3, p less than .0007; and 9.2 +/- 9.8 cm3 vs. 0.7 +/- 0.7 cm3, p less than .0007). Ejection fractions (ultrasonography/cholescintigraphy) were lower in the diabetic patients compared with the control subjects (59.9 +/- 26.6% and 63.1 +/- 23.2% vs. 73.2 +/- 23.8% and 75.3 +/- 24.8%), however, this difference was not statistically significant. Sonographically and scintigraphically determined ejection fractions were closely correlated (r = 0.90, p less than .00005).
Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer
Lu, Wei; Cao, Yang; Zhang, Yijian; Li, Sheng; Gao, Jian; Wang, Xu-An; Mu, Jiasheng; Hu, Yun-Ping; Jiang, Lin; Dong, Ping; Gong, Wei; Liu, Yingbin
Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. PMID:27283076
Four primary malignant neoplasms in a single patient
Craig, D.M.; Triedman, L.J.
A 60-year-old Caucasian male, with a previous history of a 10-year occupational exposure to ionizing radiation, chemical carcinogens, and a long history of tobacco and alcohol abuse, developed synchronous squamous cell carcinoma of the floor of the mouth and adenocarcinoma of the lung. Four years later, squamous cell carcinoma of the larynx followed by squamous cell carcinoma of the tongue were diagnosed. In this case report, we suggest that increased exposure to multiple carcinogenic factors may result in an increased incidence of both synchronous and metachronous primary malignant neoplasms.
Fine-Needle Aspiration in the Evaluation of Thyroid Neoplasms.
Oertel, Yolanda C.
Fine-needle aspiration (FNA) is a safe, rapid, and accurate diagnostic tool. Although it continues to gain acceptance, the pace is slow. Probably, if more pathologists master the basics (i.e., learn how to obtain a good sample), this simple technique could be utilized to its fullest advantage. If the sample is not adequate or representative of the lesion, the diagnosis will not be correct. Based on personal experience, we believe that suction should be minimal when obtaining thyroid aspirates. Cytologic diagnostic criteria for the most common neoplasms of the thyroid gland are provided.
Endoscopic Ultrasound-Guided Therapies in Pancreatic Neoplasms
Yang, Dennis; DiMaio, Christopher J.
Endoscopic ultrasound (EUS) has evolved from being primarily a diagnostic modality into an interventional endoscopic tool for the management of both benign and malignant gastrointestinal illnesses. EUS-guided therapy has garnered particular interest as a minimally invasive approach for the treatment of pancreatic cancer, a disease often complicated by its aggressive course and poor survival. The potential advantage of an EUS-guided approach revolves around real-time imaging for targeted therapy of a difficult to reach organ. In this review, we focus on EUS-guided therapies for pancreatic neoplasms. PMID:25802863
Contiguous but dissimilar epithelial neoplasms of the urinary bladder
Tapp, E.; Morrison, D.
An unusual tumour of the urinary bladder is described. It consists of two distinct nodules each with a quite different histological appearance, one being mucus-secreting adenocarcinoma, the other transitional cell carcinoma. Where the nodules are in contact there is little intermingling of the two histological patterns and it is suggested that the findings are probably due to the collision of two separate neoplasms. Metaplastic changes are present in the bladder mucosa adjacent to the tumour. The significance of these changes in the pathogenesis of adanocarcinoma is discussed. Images PMID:4301687
Endoscopic Diagnosis of Leiomyosarcoma of the Esophagus, a Rare Neoplasm
Torre, Massimo; Zanasi, Giulio; Vanini, Marco; Camozzi, Mario
We report a case of leiomyosarcoma of the distal third of the esophagus in a 51-year-old woman presenting with a six-month history of severe epigastric pain, disphagia and weight loss. The diagnosis, suspected on endoscopic examination, was preoperatively acheived by biopsy and immunohistological stain. Surgical treatment was undertaken with good results. Differentiation between leiomyosarcoma and more common esophageal neoplasm may be difficult if based on radiographic and endoscopic appearance. Preoperative histological confirmation is therefore mandatory to schedule a wide surgical excision. PMID:18493479
Endoscopic diagnosis of leiomyosarcoma of the esophagus, a rare neoplasm.
Ravini, M; Torre, M; Zanasi, G; Vanini, M; Camozzi, M
We report a case of leiomyosarcoma of the distal third of the esophagus in a 51-year-old woman presenting with a six-month history of severe epigastric pain, disphagia and weight loss. The diagnosis, suspected on endoscopic examination, was preoperatively acheived by biopsy and immunohistological stain. Surgical treatment was undertaken with good results. Differentiation between leiomyosarcoma and more common esophageal neoplasm may be difficult if based on radiographic and endoscopic appearance. Preoperative histological confirmation is therefore mandatory to schedule a wide surgical excision.
Unusual malignant neoplasms of ovary in children: two cases report
Bouden, Aicha; Gasmi, Manef; Hamzaoui, Mourad
Sex cord tumors with annular tubules are known to originate from the sex cord of embryonic gonads that synthesize Sertoli cells, Leydig cells, granulosa cells, and theca cells of the ovarian stroma, while ovarian small cell carcinoma of the hypercalcemic type is a type of neuroendocrine tumor. Both these tumors are uncommon, potentially malignant neoplasms in children. We report the case of a sex cord tumor with annular tubules in an 11-year-old girl and a case of small cell carcinoma of the hypercalcemic type in a 10-year-old girl. We also discuss the prognosis and management of these tumors. PMID:28018460
Uterine rupture due to invasive metastatic gestational trophoblastic neoplasm.
Bruner, David I; Pritchard, Amy M; Clarke, Jonathan
While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia.
Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms.
Tan, Huangying
Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from the endocrine cells of stomach. Most g-NENs progresses slowly and have a long disease course; however, some other g-NENs grow rapidly, similar to the progression of gastric adenocarcinoma. g-NENs have complex and diverse clinical manifestations and their prognosis and treatment strategies depend highly on clinical subtype, pathological grade, tumour stage, and other factors. Due to their low prevalence, most clinicians have limited knowledge about g-NENs. Missed diagnosis and excessive/inadequate treatment is common in clinical settings. Thus, the diagnosis and treatment of g-NENs needs to be further standardized.
[Intraductal papillary mucinous neoplasm of the pancreas, IPMN].
Sirén, Jukka
With the development and increasing use of imaging techniques, intraductal papillary mucinous neoplasm (IPMN) is being detected with increasing frequency. Two forms of the disease are distinguished, the rare main duct form and the common accessory pancreatic duct form. The former often progresses to malignancy, the latter only seldom. The mixed form of IPMN exhibits features of both forms. In main duct IPMN, mucin production obstructs the pancreatic duct causing its dilatation and often symptoms typical of chronic pancreatitis. Main duct IPMN is always an indication for surgery, whereas monitoring is often sufficient for side duct IPMN.
[Secondary neoplasms of the larynx from a colonic adenocarcinoma].
Dadkhah, Naser; Hahn, Christoffer
Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, followed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely rare. Tumours spreading to the larynx may be asymptomatic or may result in hoarseness, stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma to the larynx usually present with disseminated disease. We present a case of an isolated laryngeal metastasis from a colonic adenocarcinoma. The patient was treated with endoscopic surgery and radiation.
Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm
Bruner, David I.; Pritchard, Amy M.; Clarke, Jonathan
While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. PMID:24106538
Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors
Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.
Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996
Incidental pancreatic cystic neoplasms in an asymptomatic healthy population of 21,745 individuals
Chang, Ye Rim; Park, Joo Kyung; Jang, Jin-Young; Kwon, Wooil; Yoon, Jeong Hee; Kim, Sun-Whe
Abstract Although incidental pancreatic cystic neoplasms are being diagnosed with increasing frequency, little is known about the accurate prevalence of pancreatic cysts in the general population. The aims of this study were to evaluate the crude prevalence rate of pancreatic cystic neoplasms in asymptomatic healthy adults, and calculate the age- and sex-adjusted nationwide prevalence rate. A total of 21,745 asymptomatic individuals who underwent abdominal computed tomography (CT) as a health screening examination were enrolled between 2003 and 2013 at the Seoul National University Hospital Healthcare System Gangnam Center. Nationwide population data of 2010 were collected from the National Statistical Office, Korea. Incidental pancreatic cystic neoplasms were found in 457 individuals whose mean age was 58.7 years. The types of neoplasms were reviewed by 2 separate designated radiologists and the final diagnosis was made as follows: intraductal papillary mucinous neoplasm: 376 (82%), serous cystic neoplasm: 19 (4%), mucinous cystic neoplasm: 7 (2%), and indeterminate cysts: 55 (12%). Eight cases underwent operation. The crude prevalence rate was 2.1% and the age- and sex-adjusted expected nationwide prevalence was 2.2%. The prevalence increased with age. Here, we reported the first large-scale study among the healthy population to find out the prevalence rate of pancreatic cystic neoplasms; the age- and sex-adjusted prevalence was 2.2%, and increased with age. Further investigations regarding the clinical implications of incidental pancreatic neoplasms are necessary. PMID:28002329
Current perspectives on pancreatic serous cystic neoplasms: Diagnosis, management and beyond
Zhang, Xiao-Peng; Yu, Zhong-Xun; Zhao, Yu-Pei; Dai, Meng-Hua
Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life. PMID:27022447
Histone Deacetylase Inhibitors Inhibit the Proliferation of Gallbladder Carcinoma Cells by Suppressing AKT/mTOR Signaling.
Zhang, Peng; Guo, Zhiyong; Wu, Ying; Hu, Ronglin; Du, Jun; He, Xiaoshun; Jiao, Xingyuan; Zhu, Xiaofeng
Gallbladder carcinoma is an aggressive malignancy with high mortality mainly due to the limited potential for curative resection and its resistance to chemotherapeutic agents. Here, we show that the histone deacetylase inhibitors (HDACIs) trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA) reduce the proliferation and induce apoptosis of gallbladder carcinoma cells by suppressing the AKT/mammalian target of rapamycin (mTOR) signaling. Gallbladder carcinoma SGC-996 cells were treated with different concentrations of TSA and SAHA for different lengths of time. Cell proliferation and morphology were assessed with MTT assay and microscopy, respectively. Cell cycle distribution and cell apoptosis were analyzed with flow cytometry. Western blotting was used to detect the proteins related to apoptosis, cell cycle, and the AKT/mTOR signaling pathway. Our data showed that TSA and SAHA reduced SGC-996 cell viability and arrested cell cycle at the G1 phase in a dose- and time-dependent manner. TSA and SAHA promoted apoptosis of SGC-996 cells, down-regulated the expression of cyclin D1, c-Myc and Bmi1, and decreased the phosphorylation of AKT, mTOR p70S6K1, S6 and 4E-BP1. Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Our results demonstrate that histone deacetylase inhibitors (HDACIs) suppress the proliferation of gallbladder carcinoma cell via inhibition of AKT/mTOR signaling. These findings offer a mechanistic rationale for the application of HDACIs in gallbladder carcinoma treatment.
Implications of the Index Cholecystectomy and Timing of Referral for Radical Resection of Advanced Incidental Gallbladder Cancer
Ausania, F; White, SA; French, JJ; Jaques, BC; Charnley, RM; Manas, DM
Introduction Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection. Methods The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19–9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed. Results Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19–9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging. Conclusions In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability. PMID:25723690
Current Status of Radiopharmaceuticals for the Theranostics of Neuroendocrine Neoplasms
Fani, Melpomeni; Kolenc Peitl, Petra; Velikyan, Irina
Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs). Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics) of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr), other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them. The Glucagon-Like Peptide-1 Receptor (GLP-1R) is highly expressed in benign insulinomas, the Cholecystokinin 2 (CCK2)/Gastrin receptor is expressed in different NENs, in particular medullary thyroid cancer, and the Glucose-dependent Insulinotropic Polypeptide (GIP) receptor was found to be expressed in gastrointestinal and bronchial NENs, where interestingly, it is present in most of the sstr-negative and GLP-1R-negative NENs. Also in the field of sstr targeting new discoveries brought into light an alternative approach with the use of radiolabeled somatostatin receptor antagonists, instead of the clinically used agonists. The purpose of this review is to present the current status and the most innovative strategies for the diagnosis and treatment (theranostics) of neuroendocrine neoplasms using a cadre of radiolabeled regulatory peptides targeting their receptors. PMID:28295000
Endoscopic submucosal dissection for colorectal neoplasms: A review
Sakamoto, Taku; Mori, Genki; Yamada, Masayoshi; Kinjo, Yuzuru; So, Eriko; Abe, Seiichiro; Otake, Yosuke; Nakajima, Takeshi; Matsuda, Takahisa; Saito, Yutaka
The introduction of colorectal endoscopic submucosal dissection (ESD) has expanded the application of endoscopic treatment, which can be used for lesions with a low metastatic potential regardless of their size. ESD has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal resection. Moreover, in the past, surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum, regardless of the depth of invasion, as endoscopic resection of these lesions was technically difficult. Therefore, a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal lesions. On the other hand, ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty, longer procedural duration, and increased risk of perforation. To diversify the available endoscopic treatment strategies for superficial colorectal neoplasms, endoscopists performing ESD need to recognize its indications, the technical issues involved in its application, and the associated complications. This review outlines the methods and type of devices used for colorectal ESD, and the training required by endoscopists to perform this procedure. PMID:25473168
A novel assay to detect calreticulin mutations in myeloproliferative neoplasms
Rosso, Valentina; Petiti, Jessica; Bracco, Enrico; Pedrola, Roberto; Carnuccio, Francesca; Signorino, Elisabetta; Carturan, Sonia; Calabrese, Chiara; Bot-Sartor, Giada; Ronconi, Michela; Serra, Anna; Saglio, Giuseppe; Frassoni, Francesco; Cilloni, Daniela
The myeloproliferative neoplasms are chronic myeloid cancers divided in Philadelphia positive (Ph+), chronic myeloid leukemia, or negative: polycythemia vera (PV) essential thrombocythemia (ET), and primary myelofibrosis (PMF). Most Ph negative cases have an activating JAK2 or MPL mutation. Recently, somatic mutations in the calreticulin gene (CALR) were detected in 56–88% of JAK2/MPL-negative patients affected by ET or PMF. The most frequent mutations in CARL gene are type-1 and 2. Currently, CALR mutations are evaluated by sanger sequencing. The evaluation of CARL mutations increases the diagnostic accuracy in patients without other molecular markers and could represent a new therapeutic target for molecular drugs. We developed a novel detection assay in order to identify type-1 and 2 CALR mutations by PNA directed PCR clamping. Seventy-five patients affected by myeloproliferative neoplasms and seven controls were examined by direct DNA sequencing and by PNA directed PCR clamping. The assay resulted to be more sensitive, specific and cheaper than sanger sequencing and it could be applied even in laboratory not equipped for more sophisticated analysis. Interestingly, we report here a case carrying both type 1 and type2 mutations in CALR gene. PMID:28031530
Multifocal Primary Neoplasms in Kidney Allografts: Evaluation of Two Cases
Ellis, Robert J.; Ng, Keng Lim; Samaratunga, Hemamali; Del Vecchio, Sharon J.; Wood, Simon T.
Renal cell carcinoma (RCC) is the fifth most common malignancy in kidney transplant recipients, with increased risk arising due to immunosuppression. De novo RCC occurrence in kidney allografts is much less common when compared with the native kidneys. Multifocal RCC in allograft kidneys is rarely described. In this report, we discuss two cases of de novo multifocal renal neoplasms in allograft kidneys. Case 1 had three distinct neoplastic lesions of >5 mm, and case 2 had four. Using the World Health Organization 2016 classification of adult renal tumours, case 1 had one clear-cell (cc) RCC (grade 3) and two papillary adenomas; all confined to the kidney. Case 2 had a nodular lesion classified as ccRCC (grade 4) with focal rhabdoid differentiation and some infiltration of renal sinus fat; a cc tubulopapillary RCC; a multilocular cystic renal neoplasm of low malignant potential; and a mucinous tubular and spindle cell carcinoma; the last three all confined to the kidney. This is the first report of mucinous tubular and spindle cell carcinoma in a kidney allograft. When considering multifocal RCC with discordant histology, it is likely that these represent independent tumourigenic events. PMID:28326280
Altered glutamyl-aminopeptidase activity and expression in renal neoplasms
Background Advances in the knowledge of renal neoplasms have demonstrated the implication of several proteases in their genesis, growth and dissemination. Glutamyl-aminopeptidase (GAP) (EC. 184.108.40.206) is a zinc metallopeptidase with angiotensinase activity highly expressed in kidney tissues and its expression and activity have been associated wtih tumour development. Methods In this prospective study, GAP spectrofluorometric activity and immunohistochemical expression were analysed in clear-cell (CCRCC), papillary (PRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Data obtained in tumour tissue were compared with those from the surrounding uninvolved kidney tissue. In CCRCC, classic pathological parameters such as grade, stage and tumour size were stratified following GAP data and analyzed for 5-year survival. Results GAP activity in both the membrane-bound and soluble fractions was sharply decreased and its immunohistochemical expression showed mild staining in the four histological types of renal tumours. Soluble and membrane-bound GAP activities correlated with tumour grade and size in CCRCCs. Conclusions This study suggests a role for GAP in the neoplastic development of renal tumours and provides additional data for considering the activity and expression of this enzyme of interest in the diagnosis and prognosis of renal neoplasms. PMID:24885240
Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
Diamond, Eli L.; Durham, Benjamin H.; Haroche, Julien; Yao, Zhan; Ma, Jing; Parikh, Sameer A.; Wang, Zhaoming; Choi, John; Kim, Eunhee; Cohen-Aubart, Fleur; Lee, Stanley Chun-Wei; Gao, Yijun; Micol, Jean-Baptiste; Campbell, Patrick; Walsh, Michael P.; Sylvester, Brooke; Dolgalev, Igor; Aminova, Olga; Heguy, Adriana; Zappile, Paul; Nakitandwe, Joy; Ganzel, Chezi; Dalton, James D.; Ellison, David W.; Estrada-Veras, Juvianee; Lacouture, Mario; Gahl, William A.; Stephens, Philip J.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.; Briggs, Samuel R.; Fasan, Omotayo; Block, Jared; Héritier, Sebastien; Donadieu, Jean; Solit, David B.; Hyman, David M.; Baselga, Jose; Janku, Filip; Taylor, Barry S.; Park, Christopher Y.; Amoura, Zahir; Dogan, Ahmet; Emile, Jean-Francois; Rosen, Neal; Gruber, Tanja A.; Abdel-Wahab, Omar
Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans Cell (LCH) and non-Langerhans (non-LCH) histiocytoses, respectively. The discovery of BRAFV600E mutations in ~50% of these patients provided the first molecular therapeutisc target in histiocytosis. However, recurrent driving mutations in the majority of BRAFV600E-wildtype, non-LCH patients are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in BRAFV600E-wildtype, non-LCH patients. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of MAP2K1- and ARAF-mutated, non-LCH patients using MEK and RAF inhibitors, respectively, resulted in clinical efficacy demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders. PMID:26566875
Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas
Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo
Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management. PMID:25110429
Endoscopic submucosal dissection for colorectal neoplasms: a review.
Sakamoto, Taku; Mori, Genki; Yamada, Masayoshi; Kinjo, Yuzuru; So, Eriko; Abe, Seiichiro; Otake, Yosuke; Nakajima, Takeshi; Matsuda, Takahisa; Saito, Yutaka
The introduction of colorectal endoscopic submucosal dissection (ESD) has expanded the application of endoscopic treatment, which can be used for lesions with a low metastatic potential regardless of their size. ESD has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal resection. Moreover, in the past, surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum, regardless of the depth of invasion, as endoscopic resection of these lesions was technically difficult. Therefore, a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal lesions. On the other hand, ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty, longer procedural duration, and increased risk of perforation. To diversify the available endoscopic treatment strategies for superficial colorectal neoplasms, endoscopists performing ESD need to recognize its indications, the technical issues involved in its application, and the associated complications. This review outlines the methods and type of devices used for colorectal ESD, and the training required by endoscopists to perform this procedure.
A double gallbladder with a common bile duct stone treated by laparoscopy accompanied by choledochoscopy via the cystic duct: A case report
Yu, Wei; Yuan, Huisheng; Cheng, Shi; Xing, Ying; Yan, Wenmao
A double gallbladder is a rare congenital malformation. The present study describes a case of double gallbladder with secondary common bile duct stones. By way of laparoscopic choledochoscopy, the exploration and removal of a common bile duct stone was performed through the cystic duct. The process involved a primary suture of the cystic duct and was performed without using a T-tube, and completed a surgical removal of the gallbladder. The present case was successfully treated by laparoscopic surgery. From a review of previous studies published in the English language, this study, to the best of our knowledge, is the first report of such a case. Therefore, laparoscopic dissection is safe for the removal of a double gallbladder and for exploration of the common duct by choledochoscopy. PMID:28101147
Role of Advanced Laryngeal Imaging in Glottic Cancer: Early Detection and Evaluation of Glottic Neoplasms.
Tibbetts, Kathleen M; Tan, Melin
Laryngeal cancer accounts for approximately 2.4% of new malignancies worldwide each year. Early identification of laryngeal neoplasms results in improved prognosis and functional outcomes. Imaging plays an integral role in the diagnosis, staging, and long-term follow-up of laryngeal cancer. This article highlights advanced laryngeal imaging techniques and their application to early glottic neoplasms.
Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms.
Inoue, Izumi; Kato, Jun; Tamai, Hideyuki; Iguchi, Mikitaka; Maekita, Takao; Yoshimura, Noriko; Ichinose, Masao
To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.
Cystic and Papillary Neoplasm at the Hepatic Hilum Possibly Originating in the Peribiliary Glands
Miyata, Takashi; Uesaka, Katsuhiko
Cystic neoplasms of the liver are divided into two types: mucinous cystic neoplasm and cystic intraductal papillary neoplasm of the bile duct. We herein report two cases of cystic and papillary neoplasm of the liver which differed from the abovementioned types. Case 1. A 70-year-old man. Radiologically, a cystic tumor measuring 20 mm in diameter was found at the hepatic hilum. Right hepatectomy was performed under a diagnosis of intrahepatic cholangiocarcinoma (iCCA) based on the imaging findings. Case 2. A 70-year-old man. Radiologically, a cystic tumor measuring 60 mm in diameter was found at the hepatic hilum. Under a diagnosis of iCCA, left hepatic trisectionectomy was performed. In both cases, endoscopic retrograde cholangiography did not demonstrate communication between the cystic tumor and adjacent bile ducts. Pathologically, these two tumors were cystic neoplasms located at the hepatic hilum and were morphologically characterized by an intracystic papillary neoplasm composed of diffuse high-grade dysplasia and associated with an invasive carcinoma. Ovarian-like stroma was not found in the capsule of these tumors. Interestingly, there were peribiliary glands near these tumors, and MUC6 was expressed in these papillary neoplasms as well as in the peribiliary glands. These neoplasms might have arisen from the peribiliary glands. PMID:27656307
Mechanism‐Based Modeling of Gastric Emptying Rate and Gallbladder Emptying in Response to Caloric Intake
Sonne, DP; Hansen, M; Bagger, JI; Lund, A; Rehfeld, JF; Alskär, O; Karlsson, MO; Vilsbøll, T; Knop, FK; Bergstrand, M
Bile acids released postprandially modify the rate and extent of absorption of lipophilic compounds. The present study aimed to predict gastric emptying (GE) rate and gallbladder emptying (GBE) patterns in response to caloric intake. A mechanism‐based model for GE, cholecystokinin plasma concentrations, and GBE was developed on data from 33 patients with type 2 diabetes and 33 matched nondiabetic individuals who were administered various test drinks. A feedback action of the caloric content entering the proximal small intestine was identified for the rate of GE. The cholecystokinin concentrations were not predictive of GBE, and an alternative model linking the nutrients amount in the upper intestine to GBE was preferred. Relative to fats, the potency on GBE was 68% for proteins and 2.3% for carbohydrates. The model predictions were robust across a broad range of nutritional content and may potentially be used to predict postprandial changes in drug absorption. PMID:28028939
A rare case of gallbladder fistulation with a 60-year-old appendicectomy scar.
Thiruchandran, Gajendiran; Joyce, Megan; Baggott, Paul James
We present an extremely unusual case of an external biliary fistula in an 87-year-old woman who presented with a 1-day history of spontaneous green discharge from a 60-year-old appendicectomy scar. Examination revealed a sinus in the right iliac fossa overlying her appendicectomy scar, with a raised white cell count and C reactive protein. A CT scan revealed a complex fistula connecting the gallbladder to the subcutaneous tissue in the right flank, which further connected inferiorly with a fistula to the previous appendicectomy scar and a small iliopsoas collection. Endoscopic retrograde cholangiopancreatography revealed several stones in the common bile duct, which were removed using a balloon catheter. The patient was further managed with a long course of antibiotics and discharged with a long-term drainage bag. A literature search revealed no previously reported cases of an external biliary fistula communicating with an appendicectomy scar.
The gallbladder of Uranoscopus scaber L. (teleost perciform fish) is lined by specialized cholecystocytes.
Gilloteaux, J; Ott, Donald W; Oldham-Ott, Carla K
The gallbladder of Uranoscopus exhibits a mucosal surface layer of simple columnar epithelium composed of specialized cholecystocytes. The apices show storage and mucous secretions, typical microvilli, and very apical projections extending deep into the luminal contents. Many organelles and heterogeneous vesicles of diverse size fill the cytoplasm, including neutral mucins, mitochondria, peroxisomes, lysosomal bodies, and lipid-rich deposits with cholesterol inclusions. The fibromuscular layer shows little blood supply and contains scattered lymph-like walls with minute cholesterol inclusions. The remaining muscular, subserosal, and serosal or adventitial layers of this species do not show any histologic differences to those of other vertebrates. It was unexpected to find cholesterol inclusions in the fatty deposits of the cholecystocytes, similar to those noted in human cholesterolosis and in some forms of hypercholesterolemia, in this teleostean. In addition, aggregations of mitochondria and anomalous mitochondrial morphologies were found that resemble oncocytoma-like changes.
Acquired factor VIII deficiency after consuming the dried gallbladder of a cobra, Naja naja
Kim, Hyun Ju; Lee, Won Sik; Lee, Young Jin; Jun, Hyun Soo; Seo, Su-Kil
Acquired factor VIII deficiency is very rare, often fatal. It is associated with pregnancy, autoimmune diseases, malignancy, and drugs, although no underlying cause is found in 50%. A 49-year-old male was referred with right shoulder bruising. The coagulation test showed a prolonged activated partial thromboplastin time. The factor VIII level was less than 1%, and the factor VIII inhibitor antibody titer was 246 Bethesda units/mL. The findings were compatible with acquired factor VIII deficiency. He had consumed the dried gallbladder of a cobra, Naja naja, for two weeks, it contained venom. After the initial treatment with factor VIII, he did not take supplemental coagulation factor VIII. The patient was readmitted with left forearm swelling. He lost consciousness suddenly and brain computed tomography (CT) revealed a subdural hematoma. Despite administering recombinant factor VII, his bleeding was not controlled and he died. PMID:21120211
In vitro dissolution of gallbladder stone by edible leaves, fruits and homoeopathic medicines
NASA Astrophysics Data System (ADS)
Das, Ishwar; Singh, Yogendra; Ansari, Shoeb A.; Agrawal, Namita R.
Gallbladder stone sample of a female patient was analysed by diagnostic, spectroscopic methods and by differential scanning calorimetry (DSC). Besides cholesterol as the major constituent, bilirubin, creatinine and blood urea were also found to be present in the sample. Bile acid (ursodeoxycholic acid) was used to study its effect on the dissolution of cholestrol present in the stone. Extracts of edible leaves and fruits (amla, lemon and mausammi) and the homoeopathic medicines Berberis vulgaris Q. Dioscorea Q. and Calcarea carb 200 in the concentration range 0-3% (v/v) were found to be effective in the dissolution process in the following sequences: B. vulgaris Q. and Dioscorea Q.> C. carb 200, lemon>mausammi, amla was found to be more effective than jamun and tulsi leaf extracts in the given concentration range.
miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer
Yang, Dong; Zhan, Ming; Chen, Tao; Chen, Wei; Zhang, Yunhe; Xu, Sunwang; Yan, Jinchun; Huang, Qihong; Wang, Jian
Gallbladder cancer represents the most common malignancy of the biliary tract and is highly lethal with less than 5% overall 5-year survival rate. Chemotherapy remains the major treatment for late-stage patients. However, insensitivity to these chemotherapeutic agents including cisplatin is common. MicroRNAs (miRNAs) have been shown as modulators of drug resistance in many cancer types. We used genome-wide gene expression analysis in clinical samples to identify miR-125b-5p down-regulated in gallbladder cancer. miR-125b-5p up-regulation promoted cell death in gallbladder cancer cells in the presence of cisplatin. In contrast, knockdown of miR-125b-5p reduced cell death in gallbladder cancer cells treated with cisplatin. Up-regulation of miR-125b-5p significantly decreased tumor growth in combination with cisplatin in a mouse model. We identified Bcl2 as a direct target of miR-125b-5p which mediates the function of miR-125b-5p in gallbladder cancer. In clinical samples, miR-125b-5p was down-regulated in gallbladder cancer whereas Bcl2 was up-regulated and their expression was inversely correlated. Moreover, low miR-125b-5p expression or high expression of Bcl2 is correlated with poor prognosis in gallbladder cancer. Taken together, our findings indicate that miR-125b-5p is a potent chemotherapy sensitizer and may function as a new biomarker for the prognosis of gallbladder cancer patients. PMID:28256505
The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors
Background Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. Methods Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). Results Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary "sludge" in Arms A/B/C was 39%/36%/27%. Conclusions Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis. Trial registration ClinicalTrials.gov NCT00448786 PMID:23679351
Characterization of a small vesicular cholesterol carrier in human gallbladder bile.
Ahrendt, S A; Fox-Talbot, M K; Kaufman, H S; Lillemoe, K D; Lipsett, P A; Pitt, H A
OBJECTIVE: Cholesterol phospholipid vesicles play an important role in the nucleation of cholesterol in bile. Recent studies have identified an additional vesicle population in human bile. In this study, the role of these small vesicles as cholesterol carriers was examined. METHODS: Gallbladder bile was obtained from 60 patients at cholecystectomy. Large vesicles, small vesicles, lamellae, and mixed micelles were separated using gel filtration chromatography. RESULTS: Small vesicles were present in bile from the majority of patients both with and without cholesterol gallstones, whereas the void volume vesicle fraction was found almost exclusively in bile from patients with cholesterol gallstones. Both large vesicular and small vesicular cholesterol increased as total bile cholesterol concentration increased; however, the cholesterol-phospholipid ratio in the large vesicle fraction from patients with cholesterol stones was significantly greater than the ratio in small vesicles (1.6 +/- 0.3 vs. 1.0 < or = 0.1, p < 0.05). Whole bile cholesterol crystal appearance time was correlated significantly with the percentage of cholesterol transported by large vesicles (r = 0.63, p < 0.001) but not with the percentage of cholesterol present in small vesicles. Finally, large vesicles isolated by gel filtration chromatography formed cholesterol crystals faster than small vesicles (5.3 +/- 2 vs. 17.4 +/- 4 days, p < 0.01). CONCLUSIONS: These data suggest that a heterogenous population of vesicles is present in human gallbladder bile. As bile becomes saturated with cholesterol, it increasingly is solubilized by both small and large vesicles. The small vesicles have relatively less cholesterol and are more stable than the larger variety, from which cholesterol is most likely to precipitate. Images Figure 2. PMID:7979611
Maxi K+ channels and their relationship to the apical membrane conductance in Necturus gallbladder epithelium
Using the patch-clamp technique, we have identified large-conductance (maxi) K+ channels in the apical membrane of Necturus gallbladder epithelium, and in dissociated gallbladder epithelial cells. These channels are more than tenfold selective for K+ over Na+, and exhibit unitary conductance of approximately 200 pS in symmetric 100 mM KCl. They are activated by elevation of internal Ca2+ levels and membrane depolarization. The properties of these channels could account for the previously observed voltage and Ca2+ sensitivities of the macroscopic apical membrane conductance (Ga). Ga was determined as a function of apical membrane voltage, using intracellular microelectrode techniques. Its value was 180 microS/cm2 at the control membrane voltage of -68 mV, and increased steeply with membrane depolarization, reaching 650 microS/cm2 at -25 mV. We have related maxi K+ channel properties and Ga quantitatively, relying on the premise that at any apical membrane voltage Ga comprises a leakage conductance and a conductance due to maxi K+ channels. Comparison between Ga and maxi K+ channels reveals that the latter are present at a surface density of 0.09/microns 2, are open approximately 15% of the time under control conditions, and account for 17% of control Ga. Depolarizing the apical membrane voltage leads to a steep increase in channel steady-state open probability. When correlated with patch-clamp studies examining the Ca2+ and voltage dependencies of single maxi K+ channels, results from intracellular microelectrode experiments indicate that maxi K+ channel activity in situ is higher than predicted from the measured apical membrane voltage and estimated bulk cytosolic Ca2+ activity. Mechanisms that could account for this finding are proposed. PMID:2362182
Progress in oncolytic virotherapy for the treatment of thyroid malignant neoplasm.
Guan, Mingxu; Romano, Gaetano; Coroniti, Roberta; Henderson, Earl E
Thyroid malignant neoplasm develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Oncolytic virotherapy has significantly progressed as therapeutics in recent years. The advance is that oncolytic viruses can be designed with biological specificity to infect, replicate and lyse tumor cells. Significant advances in virotherapy have being achieved to improve the accessibility, safety and efficacy of the treatment. Therefore, it is necessary to summarize and bring together the main areas covered by these investigations for the virotherapy of thyroid malignant neoplasm. We provide an overview of the progress in virotherapy research and clinical trials, which employ virotherapy for thyroid malignant neoplasm as well as the future prospect for virotherapy of thyroid malignant neoplasms.
Pembrolizumab in Treating Patients With HIV and Relapsed, Refractory, or Disseminated Malignant Neoplasms
AIDS-Related Non-Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Locally Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Hepatocellular Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Kaposi Sarcoma; Recurrent Malignant Neoplasm; Recurrent Melanoma of the Skin; Recurrent Non-Hodgkin Lymphoma; Recurrent Non-Small Cell Lung Carcinoma; Refractory Hodgkin Lymphoma; Refractory Malignant Neoplasm; Solid Neoplasm; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Hepatocellular Carcinoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Skin Melanoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma
A putative role of ribonuclear inclusions and MBNL1 in the impairment of gallbladder smooth muscle contractility with cholelithiasis in myotonic dystrophy type 1.
Cardani, R; Mancinelli, E; Saino, G; Bonavina, L; Meola, G
Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by expansion of unstable trinucleotide (CTG) repeats at 3' untranslated region of the DMPK gene on chromosome 19q13.3. Mutant transcripts are retained in muscle nuclei as ribonuclear inclusions and interact with RNA-binding proteins, such as muscleblind-like protein 1 (MBNL1), leading to a reduction in their activity. The reduced MBNL1 activity has been associated to skeletal and cardiac muscle dysfunction. However, other organs and systems may be involved. It has been reported that 25-50% of DM1 patients have abdominal symptoms due to cholelithiasis or gallstones. Since impaired gallbladder motility plays an important role in gallstones formation, we have analyzed by FISH combined with MBNL1-immunofluorescence, the gallbladder obtained from a woman affected by DM1 who required a cholecystectomy at the age of 30. Gallbladders obtained from two no-DM1 subjects have been used as controls. Ribonuclear inclusions and MBNL1 foci accumulate and colocalize in nuclei of DM1 gallbladder smooth muscle cells. On the contrary, no ribonuclear inclusions are detectable in cell nuclei of control gallbladders and MBNL1 is uniformly distributed in smooth muscle cell nuclei. These results suggest that nuclear accumulation of MBNL1 and ribonuclear inclusions may have a direct adverse effect on gallbladder smooth muscle contractility and thus contribute to gallstones formation in DM1 patients.
C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal
Feng, Hua; Wang, Fang; Wang, Changmiao
Objective(s): To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs). Materials and Methods: A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments. Results: C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. Conclusion: Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips. PMID:27635195
Subsequent neoplasms of the CNS among survivors of childhood cancer: a systematic review.
Bowers, Daniel C; Nathan, Paul C; Constine, Louis; Woodman, Catherine; Bhatia, Smita; Keller, Karen; Bashore, Lisa
Childhood cancer survivors are at risk for development of subsequent neoplasms of the CNS. Better understanding of the rates, risk factors, and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer could lead to more informed screening guidelines. Two investigators independently did a systematic search of Medline and Embase (from January, 1966, through March, 2012) for studies examining subsequent neoplasms of the CNS among survivors of childhood cancer. Articles were selected to answer three questions: what is the risk of CNS tumours after radiation to the cranium for a paediatric cancer, compared with the risk in the general population; what are the outcomes in children with subsequent neoplasms of the CNS who received CNS-directed radiation for a paediatric cancer; and, are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 were included in this Review. These studies reported that childhood cancer survivors have an 8·1-52·3-times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation, and some studies showed a correlation between radiation dose and risk of subsequent CNS tumours. 5-year survival ranged from 0-19·5% for subsequent high-grade gliomas and 57·3-100% for meningiomas, which are similar rates to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up, and small sample sizes. We conclude that survivors of childhood cancer who received cranial radiation therapy have an increased risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms.
Hematologic neoplasms: interpreting lung findings in chest computed tomography.
Calvillo Batllés, P; Carreres Polo, J; Sanz Caballer, J; Salavert Lletí, M; Compte Torrero, L
Lung disease is very common in patients with hematologic neoplasms and varies in function of the underlying disease and its treatment. Lung involvement is associated with high morbidity and mortality, so it requires early appropriate treatment. Chest computed tomography (CT) and the analysis of biologic specimens are the first line diagnostic tools in these patients, and sometimes invasive methods are necessary. Interpreting the images requires an analysis of the clinical context, which is often complex. Starting from the knowledge about the differential diagnosis of lung findings that radiologists acquire during training, this article aims to explain the key clinical and radiological aspects that make it possible to orient the diagnosis correctly and to understand the current role of CT in the treatment strategy for this group of patients.
Gastroenteropancreatic (neuro)endocrine neoplasms: the histology report.
Rindi, Guido; Bordi, C; La Rosa, S; Solcia, E; Delle Fave, Gianfranco
Based on the year 2000 World Health Organization (WHO) classification and the European Neuroendocrine Tumor Society (ENETS) grading and staging proposals, we here define the minimal guidelines for pathology reporting of (neuro)endocrine neoplasms. The macroscopical description is recommended according to standard procedures and the microscopical description according to recognized architectural and cytological features for endocrine lesions. Minimal diagnostic immunohistochemistry entails the use of chromogranin A, synaptophysin and Ki67. Other potentially useful tests are those for CD56 N-CAM, PGP 9.5 and hormones for diagnosis, the somatostatin receptor subtype 2 for potential radiodiagnostics and therapy, and transcription factors like TTF1 and CDX2, for site of origin. Grading definition is always mandatory as well as TNM staging for surgical specimens.
Molecular insights into regulation of JAK2 in myeloproliferative neoplasms
Hubbard, Stevan R.
The critical role of Janus kinase-2 (JAK2) in regulation of myelopoiesis was established 2 decades ago, but identification of mutations in the pseudokinase domain of JAK2 in myeloproliferative neoplasms (MPNs) and in other hematologic malignancies highlighted the role of JAK2 in human disease. These findings have revolutionized the diagnostics of MPNs and led to development of novel JAK2 therapeutics. However, the molecular mechanisms by which mutations in the pseudokinase domain lead to hyperactivation of JAK2 and clinical disease have been unclear. Here, we describe recent advances in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations lead to constitutive activation of JAK2. PMID:25824690
Clinical management of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes
Clara, Joseph A.; Sallman, David A.; Padron, Eric
The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of next-generation platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis, prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts. PMID:27807503
Management of metastatic spinal column neoplasms--an update.
Araujo, João Luiz Vitorino; Veiga, José Carlos Esteves; Figueiredo, Eberval Gadelha; Barboza, Victor Rosseto; Daniel, Jefferson Walter; Panagopoulos, Alexandros Theodoros
The increased survival of cancer patients due to the improvement and advancement of therapeutic modalities has promoted progressive increase in the prevalence of metastatic tumors of the spine, making it important for healthcare professionals to acquire knowledge in the field. Spinal column metastases are usually secondary to malignant neoplasm of the breast, lung and prostate, male gender being the most often affected and pain being the initial symptom in 90% of patients. It is estimated that 30-90% of terminally ill patients with cancer have metastases at some spinal column segment. Clinical history, physical and neurological assessments are critical to determine the degree and extent of the lesion, and therefore choose the appropriate imaging method to be requested. This study aims to perform a review and didactic description of the main aspects related to the physiopathology, diagnosis and treatment of this disease.
JAK2 GGCC haplotype in MPL mutated myeloproliferative neoplasms.
Pietra, Daniela; Casetti, Ilaria; Da Vià, Matteo C; Elena, Chiara; Milanesi, Chiara; Rumi, Elisa
JAK2 (V617F) is associated with a genetic predisposition to its acquisition,as it is preferentially found in subjects with a common constitutional JAK2 haplotype known as 46/1 or GGCC. A recent study suggests that a genetic predisposition to acquisition of MPL mutation may exist in sporadic patients, since an association was found with the JAK2 46/1 haplotype. We genotyped 509 patients with myeloproliferative neoplasms (MPN), 7% of which carrying a somatic mutation of MPL Exon 10. We found that the JAK2 GGCC haplotype was closely associated with JAK2 (V617F) (OR 1.84, P < 0.001) but not with MPL mutations (OR 0.98), suggesting a different genetic background for these molecular lesions.
Localization of gonadotropin binding sites in human ovarian neoplasms
Nakano, R.; Kitayama, S.; Yamoto, M.; Shima, K.; Ooshima, A. )
The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms.
Dermoscopy of benign and malignant neoplasms in the pediatric population.
Haliasos, Helen C; Zalaudek, Iris; Malvehy, Josep; Lanschuetzer, Christoph; Hinter, Helmut; Hofmann-Wellenhof, Rainer; Braun, Ralph; Marghoob, Ashfaq A
Dermoscopy is a noninvasive technique that enables visualization of subsurface colors and structures within the skin that are imperceptible to the naked eye. The dermatoscope allows the physician to examine both the macroscopic and microscopic primary morphology of skin lesions, identify subtle clinical clues, confirm naked-eye clinical diagnoses, and monitor treatment progress while posing little threat to the young patient. Dermoscopic findings have been formulated into diagnostic criteria that assist experienced clinicians in differentiating benign and malignant neoplasms. In this review, clinical morphology of melanocytic nevi and melanoma in the pediatric population is examined and the relevant dermoscopic findings and histopathologic correlates that aid in the diagnosis and management of these lesions are described.
Application of FT IR microspectroscopy in diagnosing thyroid neoplasms
NASA Astrophysics Data System (ADS)
Schultz, Christian P.; Liu, Kan-Zhi; Salamon, Elizabeth A.; Riese, Karl T.; Mantsch, Henry H.
Tissue biopsies and fine-needle aspirates (FNA) of patients with suspected benign or malignant thyroid neoplasms were investigated by infrared microspectroscopy and multivariate statistical methods. Unsupervised cluster analysis revealed four different spectral patterns for the aspirates analyzed, corresponding to colloid goiter, adenoma, carcinomas and negative diagnoses. Infrared microspectroscopic measurements of neoplastic cells on infrared transparent slides provide a potentially new tool for diagnostic screening of these FNA. Biopsy material obtained during surgical removal of gland tissue, was successfully used to generate statistically significant criteria for the distinction of neoplastic from normal tissue. Bivariate histogram plots demonstrate that two selected parameters, DNA and protein, are sufficient to separate control tissue from adenoma and carcinomas
Brain Neoplasm and the Potential Impact on Self-Identity.
Anderson-Shaw, Lisa; Baslet, Gaston; Villano, J Lee
Cancers of the brain can cause alterations in a person's neurocognitive abilities, and in some patients can even challenge their concept of self and self-identity. Cancer treatment may offer some hope for longer survival, but residual neurocognitive alterations generally remain. Individualized care for these patients should include information related to anticipated effects of their disease or treatments affecting their perception or expression of self. At present, the concepts of self and self-identity are largely unexplored in neuro-oncology, but we will discuss this clinical population in order to highlight the need for further clinical evaluation of these phenomena among patients with brain neoplasm. Finally, we will briefly note the need for a clinical tool to assess self and self-identity changes in brain tumor patients.
Gastric neuroendocrine neoplasm with liver metastases: a case report
Chen, Xiao
A 39-year-old women was admitted to our department with gastric mass and multiple liver space-occupying lesions found during health check-up. A gastroscopy showed an irregular ridge-like lesion at the lesser curvature of the stomach body (about 40 cm away from the incisor tooth); the pathological and immunohistochemical findings demonstrated the presence of a neuroendocrine tumor of well-differentiated (G1). An abdominal MRI indicated the possibility of multiple liver metastases and multiple perigastric lymph node metastases. After eight cycles of sandostatin treatment, a proximal subtotal gastrectomy + right hepatectomy + left partial hepatectomy + cholecystectomy were performed, and the diagnosis of gastric neuroendocrine neoplasm (gNEN) with liver metastases was confirmed. The patient recovered smoothly after operation and received sandostatin treatment just as pre-operation. We report a case of a gNEN with metastases by multimodality therapy with a view of the literature. PMID:28138622
Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms
Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone. PMID:28028026
Computed tomographic characteristics of odontogenic neoplasms in dogs.
Amory, Joseph T; Reetz, Jennifer A; Sánchez, Melissa D; Bradley, Charles W; Lewis, John R; Reiter, Alexander M; Mai, Wilfried
Odontogenic neoplasms are locally invasive oral tumors in dogs. The purpose of this retrospective study was to describe CT characteristics for varying histopathologic types of canine odontogenic neoplasms. A board-certified veterinary radiologist who was unaware of histologic findings reviewed and scored imaging studies. A total of 29 dogs were included in the study. Twenty-three of these dogs had concurrent dental radiographs. The most common CT characteristics for all tumor types were a direct association with or in the region of multiple teeth in 96.4% (27/28), contrast enhancement in 96.3% (26/27), alveolar bone lysis in 93.1% (27/29), and mass-associated tooth displacement in 85.2% (23/27). Mass-associated cyst-like structures were identified in 53.6% (15/28) and were only present in tumors containing odontogenic epithelium. Canine acanthomatous ameloblastomas (n = 15) appeared as extra-osseous (10/15) or intra-osseous (5/15) masses. Intra-osseous canine acanthomatous ameloblastomas were more likely to have mass-associated cyst-like structures and were subjectively more aggressive when compared with extra-osseous canine acanthomatous ameloblastomas. Amyloid-producing odontogenic tumors (n = 3) had subjectively uniform CT imaging characteristics and consisted of round soft tissue and mineral attenuating masses with multiple associated cyst-like structures. Fibromatous epulides of periodontal ligament origin (n = 4) were contrast enhancing extra-osseous masses that were rarely referred for CT examinations and 25% (1/4) were not visible with CT. Other odontogenic tumors were less represented or had more variable CT imaging characteristics. Mass-associated tooth destruction was appreciated more often with dental radiographs and extra-oral tumor extension was identified more often with CT.
Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms.
Rumi, Elisa; Cazzola, Mario
Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone.
Recurrent genetic defects on chromosome 5q in myeloid neoplasms
Hosono, Naoko; Mahfouz, Reda; Przychodzen, Bartlomiej; Yoshida, Kenichi; Jerez, Andres; LaFramboise, Thomas; Polprasert, Chantana; Clemente, Michael J; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Sanada, Masashi; Cui, Edward; Verma, Amit K; McDevitt, Michael A; List, Alan F; Saunthararajah, Yogen; Sekeres, Mikkael A; Boultwood, Jacqueline; Ogawa, Seishi
Background Deletion of chromosome 5q (del(5q)) is the most common karyotypic abnormality in myeloid neoplasms. Materials and Methods To define the pathogenic molecular features associated with del(5q), next–generation sequencing was applied to 133 patients with myeloid neoplasms (MDS; N = 69, MDS/MPN; N = 5, sAML; N = 29, pAML; N = 30) with del(5q) as a sole abnormally or a part of complex karyotype and results were compared to molecular features of patients diploid for chr5. Findings A number of 5q genes with haploinsufficient expression and/or recurrent somatic mutations were identified; for these genes, CSNK1A1 and G3BP1 within the commonly deleted 5q region and DDX41 within a commonly retained region were most commonly affected by somatic mutations. These genes showed consistent haploinsufficiency in deleted cases; low expression/mutations of G3BP1 or DDX41 were associated with poor survival, likely due to decreased cellular function. The most common mutations on other chromosomes in patients with del(5q) included TP53, and mutations of FLT3 (ITD or TKD), NPM1 or TET2 and were mutually exclusive. Serial sequencing allowed for definition of clonal architecture and dynamics, in patients with exome sequencing allelic imbalance for informative SNPs facilitated simultaneous approximation of clonal size of del(5q) and clonal burden for somatic mutations. Interpretation Our results illuminate the spectrum of molecular defects characteristic of del(5q), their clinical impact and succession of stepwise evolution. PMID:28031539
A Solitary Metastasis for a Malignant Schwannoma in the Gallbladder Detected by 18F-FDG PET/CT.
Evangelista, Laura; Burei, Marta; Basso, Umberto
A 63-year-old woman with a history of malignant schwannoma in the left shoulder (pT1aNxMx) was treated with surgical resection in 2012. During follow-up, patient developed a metastasis in the right lung treated by further surgical intervention. For a suspicion on persistent disease in the lung, patient was sent to FDG PET/CT examination, which showed a focal uptake in the gallbladder. The patient underwent cholecystectomy, and a solitary metastasis from schwannoma was diagnosed by pathology. This case highlights that, in patients with a malignant schwannoma, a careful differential diagnosis should be made in case of a significant FDG uptake in the gallbladder.
Parasitic Infection of the Gallbladder: Cystoisospora belli Infection as a Cause of Chronic Abdominal Pain and Acalculous Cholecystitis.
Martelli, Matthew G; Lee, Johnathan Y
Herein we describe two cases of Cystoisospora belli infection of the gallbladder in patients with chronic abdominal pain and review the published literature to date. C. belli is an intracellular protozoan parasite that typically infects the small bowel of immunocompromised hosts. Little is known of the significance of C. belli infection of the gallbladder at this point as only four cases have been reported as yet, only one of which occurred in an immunocompetent patient. It is often treatable with antibiotics, and the patient's immune status, including HIV testing, should be investigated. Neither of the patients at our institution was found to be immunocompromised, and HIV-1/2 antibody testing was non-reactive in both.
The effects of caerulein and a meal stimulus on gallbladder intraluminal pressure and bile flow in the pig.
Mitchenere, P; Adrian, T E; Hobbs, K E; Bloom, S R
The intraluminal gallbladder pressure has been measured in a conscious unsedated pig model by the use of a radiotelemetry pressure capsule. A loop fistula was incorporated to measure bile output simultaneously. Mean fasting intraluminal gallbladder pressure was found to be 15 +/- 4 mmHg above atmospheric pressure, and mean fasting bile output 7.5 +/- 0.8 ml/10 min. Following intravenous caerulein pressure peaked at 2 min with a mean rise of 17 +/- 3 mmHg above basal (P less than 0.005). Bile output was increased for 30 min following caerulein with a total mean increase for this period of 13.5 +/- 2.2 ml (P less than 0.005). Gallbladder pressure rose significantly 5 min after commencing a meal by 6.0 +/- 1.9 mmHg (P less than 0.025) reaching a peak pressure 65 min after the meal with a mean rise of 14.8 +/- 2.3 mmHg (P less than 0.005). Bile output was significantly increased for 50 min following the ingestion of food. The total increments above basal values for bile output being 15.9 +/- 2.7 ml (P less than 0.005) in the first 30 min post-prandially and 1.6 +/- 2.4 ml (P less than 0.005) in the 30--60 min period. This model re-emphasizes the rapidity of the hormonal response and may be valuable for further studies on the physiology of post-prandial gallbladder emptying.
Enhancement of intragastric acid stability of a fat emulsion meal delays gastric emptying and increases cholecystokinin release and gallbladder contraction.
Marciani, Luca; Wickham, Martin; Singh, Gulzar; Bush, Debbie; Pick, Barbara; Cox, Eleanor; Fillery-Travis, Annette; Faulks, Richard; Marsden, Charles; Gowland, Penny A; Spiller, Robin C
Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories.
The Laparoscopic Re-Exploration in the Management of the Gallbladder Remnant and the Cystic Duct Stump Calculi
Kumar, Satendra; Afaque, Yusuf; Bhartia, Abhishek; Bhartia, Vishnu Kumar
Introduction The gallbladder remnant and the cystic duct stump calculi are uncommon causes of post-cholecystectomy syndrome. Re-exploration is usually needed in the cases where symptom persists. Very few case series and reports are available regarding laparoscopic re-exploration. Aim To assess the safety and feasibility of Laparoscopic re-exploration in the cases of gallbladder remnant and cystic duct stump calculi leading to post cholecystectomy syndromes. Materials and Methods In this study, laparoscopic re-explorations was done in 22 patients in which 17 patients had gallbladder remnant calculi and 5 had cystic duct stump calculi. The study considered parameters like the operative time, conversion rate, post-operative complications, post-operative hospital stay and mortality in these patients. The duration of study was 15 years and the data was retrospectively reviewed. Results The median operating time was 83 minutes (range 51 to 134 minutes). Only one patient had conversion to open surgery. In postoperative period two patients had bile leak. They were managed conservatively and leak subsided in 8 and 11 days respectively. One patient had postoperative bleeding not requiring blood transfusion. There was no major complication requiring further intervention and no mortality. Patients were discharged on median day 4 (range 2-11) after the surgery. Patients were followed up every 3 months for one year. However, out of these three patients did not turn up for follow-up. Conclusion In expert hands laparoscopic re-exploration of the gallbladder remnant/cystic duct stump calculi can be performed within a reasonable operating time. The conversion to conventional re–exploration rate was very low with minimal post-operative complications and shorter hospital stay. PMID:27656498
Morphological and physiological evidence for interstitial cell of Cajal-like cells in the guinea pig gallbladder.
Lavoie, Brigitte; Balemba, Onesmo B; Nelson, Mark T; Ward, Sean M; Mawe, Gary M
Gallbladder smooth muscle (GBSM) exhibits spontaneous rhythmic electrical activity, but the origin and propagation of this activity are not understood. We used morphological and physiological approaches to determine whether interstitial cells of Cajal (ICC) are present in the guinea pig extrahepatic biliary tree. Light microscopic studies involving Kit tyrosine kinase immunohistochemistry and laser confocal imaging of Ca(2+) transients revealed ICC-like cells in the gallbladder. One type of ICC-like cell had elongated cell bodies with one or two primary processes and was observed mainly along GBSM bundles and nerve fibres. The other type comprised multipolar cells that were located at the origin and intersection of muscle bundles. Electron microscopy revealed ICC-like cells that were rich in mitochondria, caveolae and smooth endoplasmic reticulum and formed close appositions between themselves and with GBSM cells. Rhythmic Ca(2+) flashes, which represent Ca(2+) influx during action potentials, were synchronized in any given GBSM bundle and associated ICC-like cells. Gap junction uncouplers (1-octanol, carbenoxolone, 18beta-glycyrrhetinic acid and connexin mimetic peptide) eliminated or greatly reduced Ca(2+) flashes in GBSM, but they persisted in ICC-like cells, whereas the Kit tyrosine kinase inhibitor, imanitib mesylate, eliminated or reduced action potentials and Ca(2+) flashes in both cell types, as well as associated tissue contractions. This study provides morphological and physiological evidence for the existence of ICC-like cells in the gallbladder and presents data supporting electrical coupling between ICC-like and GBSM cells. The results support a role for ICC-like cells in the generation and propagation of spontaneous rhythmicity, and hence, the excitability of gallbladder.
Four new species of Ceratomyxa Thelohan 1892 (Myxozoa: Myxosporea: Ceratomyxidae) infecting the gallbladder of some Red Sea fishes.
Abdel-Ghaffar, F; Ali, M A; Al Quraishy, S; Al Rasheid, K; Al Farraj, S; Abdel-Baki, A S; Bashtar, A-R
Four new Ceratomyxa species were described from the gallbladder of four Red Sea fishes at Suez and Hurghada, Egypt. These species are Ceratomyxa bassoni sp. n. from Plectorhinchus gaterinus (Forsskal 1775) at Suez and Hurghada, Ceratomyxa entzerothi sp. n. from Valamugil seheli (Forsskal 1775) at Suez and Hurghada, Ceratomyxa swaisi sp. n. from Saurida undosquamis (Richardson 1848) at Suez only and Ceratomyxa hurghadensis sp. n. from Fistularia commersonii Ruppell 1838 at Hurghada only. Their taxonomic affinities to other species are discussed.
Overexpression of the HER2/neu Gene: A New Therapeutic Possibility for Patients With Advanced Gallbladder Cancer
de Toro, Gonzalo; Schalper, Kurt; de Aretxabala, Xabier; Churi, Chaitanya; Javle, Milind
ABSTRACT BACKGROUND: The HER2/neu gene is a proto-oncogene that can predict the response to treatment with trastuzumab, pertuzumab, and lapatinib. This study was conducted to determine the frequency of HER2/neu overexpression and to identify a subgroup of patients with gallbladder cancer who would benefit from targeted therapy. METHODS: Patients with gallbladder cancer (n = 187; 165 women and 22 men) with a recorded follow-up of at least 5 years were included, along with control subjects (n = 75). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP/ASCO (College of American Pathologists/American Society of Clinical Oncology) criteria for breast cancer. RESULTS: Overexpression of HER2/neu was observed in 12.8% of the cases. Of those, 0% were mucosal, 14.3% muscular, 12.8% subserosal, and 10.6% serosal. In 20% of the cases, equivocal staining was observed. Overexpression was more frequent in the advanced cancers and in the better differentiated tumors (13.8% and 17.4%, respectively), but the difference was nonsignificant. The patients with overexpression of HER2/neu had a worse overall survival, when compared with those who had no expression at 5 years (34% vs. 41%). CONCLUSION: This is the single largest study of HER2/neu expression in gallbladder cancer to use commonly accepted scoring criteria. The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases. This subgroup may benefit from inhibitors of the HER2/neu pathway. PMID:24799970
[Utility of bone marrow biopsy in the diagnosis of myeloproliferative neoplasm].
Tovar-Bobadilla, José Leonard; Ortiz-Hidalgo, Carlos
A diagnostic approach of myeloproliferative neoplasms, according to the 2008 WHO classification system for hematological malignancies, has to consider clinical, molecular, and cytogenetic information as well as bone marrow histology. A diagnosis of chronic myeloid leukemia requires the presence of BCR-ABL-1, and the Philadelphia chromosome-negative (Ph-1-negative) myeloproliferative neoplasms constitute three main subtypes, including primary myelofibrosis, polycythemia rubra vera, and essential thrombocythemia. These three Ph-1-negative myeloproliferative neoplasms share many pathogenic characteristic such as JAK2 mutations; however, they differ in prognosis, progression to myelofibrosis, and risk of leukemic transformation. There are currently various major points of interest in bone marrow examination in myeloproliferative neoplasms. One is the morphology of megakaryocytes, which are the hallmark of Ph-1-negative myeloproliferative neoplasms and play a crucial role in separating the different subtypes of myeloproliferative neoplasms. Another is reticulin fibrosis or collagen fibrosis, which may only be detected on a bone marrow biopsy specimen by reticulin and trichrome stains, respectively, and immunohistochemistry and certain molecular techniques may be applied in bone marrow biopsies as supporting evidence of certain features of myeloproliferative neoplasms.
Neoplasm seeding in biopsy tract of the musculoskeletal system. A systematic review
Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; da Silva, Hilton Justino; de Mello, Roberto José Vieira
To identify, through a systematic literature review, the characteristics of neoplasm seeding in biopsy performed on the musculoskeletal system. We performed a search on PubMed, MEDLINE, LILACS and SciELO from August to October 2010. We included articles that addressed the neoplasm seeding in biopsy performed on the musculoskeletal system. The search was limited to English, Spanish and Portuguese as publication languages, but it was not limited by year of publication. We retrieved 2858 articles, but only seven were selected based on inclusion and exclusion criteria. Other four papers were found in the references of selected articles, totalizing 11 articles that were used to perform this systematic review. Issues may be raised in the literature: age and gender don't seem to influence the occurrence of neoplasm seeding; without resection of the biopsy tract, the possibility of local recurrence is very real; the influence of the type of tumor in the occurrence of neoplasm seeding is uncertain; it is impossible to conclude whether the closed biopsy technique has a lower chance of neoplasm seeding; it is likely that adjuvant chemotherapy has a protective effect against neoplasm seeding; an unfavorable prognosis is expected according to neoplasm seeding results. PMID:24899866