text:
The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma.
Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC. PMID:24859531
Liu, Chen; Karam, Rachid; Zhou, YingQi; Su, Fang; Ji, Yuan; Li, Gang; Xu, GuoTong; Lu, LiXia; Wang, ChongRen; Song, MeiYi; Zhu, JingPing; Wang, YiRan; Zhao, YiFan; Foo, Wai Chin; Zuo, MingXin; Valasek, Mark A; Javle, Milind; Wilkinson, Miles F; Lu, YanJun
Surgical outcome of adenosquamous carcinoma of the pancreas.
Adenosquamous carcinoma is rare, accounting for 3%-4% of all pancreatic carcinoma cases. These tumors are characterized by the presence of variable proportions of mucin-producing glandular elements and squamous components, the latter of which should account for at least 30% of the tumor tissue. Recently, several reports have described cases of adenosquamous carcinoma of the pancreas. However, as the number of patients who undergo resection at a single institute is limited, large studies describing the clinicopathological features, therapeutic management, and surgical outcome for adenosquamous carcinoma of the pancreas are lacking. We performed a literature review of English articles retrieved from Medline using the keywords 'pancreas' and 'adenosquamous carcinoma'. Additional articles were obtained from references within the papers identified by the Medline search. Our subsequent review of the literature revealed that optimal adjuvant chemotherapy and/or radiotherapy regimens for adenosquamous carcinoma of the pancreas have not been established, and that curative surgical resection offers the only chance for long-term survival. Unfortunately, the prognosis of the 39 patients who underwent pancreatic resection for adenosquamous carcinoma was very poor, with a 3-year overall survival rate of 14.0% and a median survival time of 6.8 mo. Since the postoperative prognosis of adenosquamous carcinoma of the pancreas is currently worse than that of pancreatic adenocarcinoma, new adjuvant chemotherapies and/or radiation techniques should be investigated as they may prove indispensible to the improvement of surgical outcomes. PMID:19058301
Okabayashi, Takehiro; Hanazaki, Kazuhiro
Adenosquamous carcinoma of the esophagogastric junction. Case report.
Adenosquamous carcinoma is a rare tumor with coexisting elements of infiltrating squamous cell carcinoma and adenocarcinoma. This tumor is reported to arise in different organs but rarely in the oesophagus. In most cases, it shows highly aggressive biological behaviour with high propensity to regional lymph-node metastasis and poor prognosis. We describe the management of a patient with an aggressive adenosquamous carcinoma of the esophagogastric junction. PMID:22668530
Francioni, F; Tsagkaropoulos, S; Telha, V; Barile La Raia, R; De Giacomo, T
Primary adenosquamous carcinoma of the esophagus
AIM: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary adenosquamous carcinoma (ASC) of the esophagus. METHODS: A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College. In 37 cases, the histological diagnosis was primary ASC. Clinical data were retrospectively analyzed from these 37 patients, who underwent transthoracic esophagectomy with lymphadenectomy. The ?2 or Fisher�s exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma (SCC). The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates. A Cox proportional hazard regression model was used to identify independent prognostic factors. RESULTS: Primary esophageal ASC accounted for 0.92% of all primary esophageal carcinoma cases (37/4015). The clinical manifestations were identical to those of other types of esophageal cancer. All of the 24 patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC. The median survival time (MST) was 21.0 mo (95%CI: 12.6-29.4), and the 1-, 3-, and 5-year overall survival rates were 67.5%, 29.4%, and 22.9%, respectively. In multivariate analysis, only adjuvant radiotherapy (HR = 0.317, 95%CI: 0.114-0.885, P = 0.028) was found to be an independent prognostic factor. The MST for ASC patients was significantly lower than that for SCC patients [21.0 mo (95%CI: 12.6-29.4) vs 46.0 mo (95%CI: 40.8-51.2), P = 0.001]. In subgroup analyses, the MST for ASC patients was similar to that for poorly differentiated SCC patients. CONCLUSION: Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy. The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.
Chen, Shao-Bin; Weng, Hong-Rui; Wang, Geng; Yang, Jie-Sheng; Yang, Wei-Ping; Liu, Di-Tian; Chen, Yu-Ping; Zhang, Hao
Case of early adenosquamous carcinoma of the stomach.
Adenosquamous carcinoma of the stomach is very rare; at present, there are only seven published reports. We report here an eighth case involving a 77-year-old Japanese man who was diagnosed with gastric cancer by upper endoscopy and computed tomography (CT). He underwent laparoscopic-assisted distal gastrectomy for early gastric cancer and the resected specimen was diagnosed as adenosquamous carcinoma limited to the submucosal layer. Only one lymph node metastasis was noted. Seven months later, liver metastasis (3 tumors, 15 mm maximum in diameter) was detected by abdominal CT. He was started on chemotherapy with S-1 and cisplatin (CDDP) and is alive 14 months after surgery. Almost all cases of adenosquamous carcinoma of the stomach are diagnosed in advanced stages and carry a very poor prognosis. Most patients with early adenosquamous carcinoma of the stomach survive for 2 or more years without recurrence, however our patient experienced recurrence 7 months after surgery. Therefore, future treatment for recurrent adenosquamous carcinoma of the stomach should be considered. PMID:24364267
Kimura, Yasue; Matsuda, Hiroyuki; Saeki, Hiroshi; Oki, Eiji; Morita, Masaru; Sugimachi, Keishi; Yamashita, Yo-ichi; Ikegami, Toru; Uchiyama, Hideaki; Yoshizumi, Tomoharu; Soejima, Yuji; Kawanaka, Hirofumi; Ikeda, Tetsuo; Tsutsui, Shinichi; Fujihara, Megumu; Mimori, Koshi; Watanabe, Masayuki; Ishida, Teruyoshi; Maehara, Yoshihiko
Primary adenosquamous carcinoma of ampulla of Vater--A rare case report
INTRODUCTION Primary adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV) is extremely rare. Carcinoma of the ampulla of Vater tends to manifest early due to biliary outflow obstruction, as opposed to pancreatic neoplasms that often are advanced at the time of diagnosis. Periampullary carcinomas are treated by pancreaticoduodenectomy (PD). Adenosquamous carcinoma carries very dismal prognosis. PRESENTATION OF CASE Here we present a case of 58-year-old male who was presented with abdominal pain, jaundice and anorexia with no history of (h/o) pruritus and clay colored stool. All blood investigations were normal except liver function tests (LFTs). Ultrasonography (USG) of abdomen suggestive of periampullary mass with dilated pancreatico-biliary tree. Endoscopic retrograde cholangiopancreatography (E.R.C.P.) demonstrated large deformed and bulky papilla with ulcerated lesion with infiltration in to duodenum. Exploratory laprotomy proceeds Whipple's pancreaticoduodenectomy done. Histopathology revealed adenocarcinoma of the ampulla of Vater. Immunohistochemistry was confirmatory of adenosquamous carcinoma. DISCUSSION Adenosquamous carcinoma (ASC) is defined as a tumor in which both glandular and squamous elements are histologically malignant. Compared to adenocarcinoma, ASC of the AmV is a rare malignancy. Preoperative diagnosis is difficult because of the lack of defining characteristics in imaging studies and the difficulty in acquiring both malignant components by limited biopsy. Periampullary carcinomas are treated by pancreaticoduodenectomy. CONCLUSION Adenosquamous carcinoma is a very rare form of cancer of the AmV. Pancreaticoduodenectomy is the treatment of choice though early recurrence and distal metastasis may be encountered after surgery. Follow-up should be more frequent to detect possible early recurrence and distal metastasis.
Kshirsagar, Ashok Y.; Nangare, Nitin R.; Vekariya, Mayank A.; Gupta, Vaibhav; Pednekar, Akshay S.; Wader, J.V.; Mahna, Abhishek
Adenosquamous Carcinoma of Vesicovaginal Fistula: A Rare Entity
A 56-year-old lady presented with a vesicovaginal fistula (VVF) along with past history of abdominal hysterectomy. Biopsy of the fistulous tract showed squamous cell carcinoma (SCC). Patient underwent radical cystourethrectomy, total vaginectomy, and bilateral pelvic lymph node dissection along with ileal conduit. The final histopathology report of the resected specimen showed adenosquamous carcinoma in VVF. As this is a rare entity, we are reporting this case.
Tabali, Rudresh; Ramkumar, Aravind
Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma
BACKGROUND: Adenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR,
Adhemar Longatto-Filho; C�line Pinheiro; Olga Martinho; Marise AR Moreira; Luiz FJ Ribeiro; Geraldo S Queiroz; Fernando C Schmitt; F�tima Baltazar; Rui M Reis
Clinical significance of PIK3CA and survivin in primary adenosquamous lung carcinoma.
The aim of this study was to evaluate the expression of PIK3CA and survivin in adenosquamous lung cancer (ASC) patients and their clinicopathological significance. A total of 32 patients with adenosquamous carcinoma and ten cases of normal lung lesion were investigated, and the expressions of PIK3CA and survivin were detected by immunohistochemistry. The PIK3CA and survivin expression in adenosquamous lung carcinoma tissues was significantly higher than those of the normal lesions (p = 0.02). The positive rate of PIK3CA and survivin expressions was in accordance with the tumor-node-metastasis stage (p = 0.002/0.013), pathological grade (p = 0.019/0.013), and lymph node metastasis (p = 0.029/0.008). Out of 15 patients with definite follow-ups, highly positive expressions of PIK3CA (12 cases) and survivin (11 cases) were suggested to be associated with adverse prognosis (nine cases recurrence and four cases died). A positive correlation was also observed between the expressions of PIK3CA and survivin (r = 0.622, p < 0.001). These findings indicated that PIK3CA and survivin up-regulation might play an important role in lymph node metastasis and adverse prognosis in ASC. Nevertheless, further additional prospective studies in the area of ASC molecular profiling are needed. PMID:24838432
Yu, Shaomin; Zhang, Zhihong; Zhang, Bin; Shu, Yongqian; Wu, Hao; Huang, Xiang; Yu, Qianqian; Guo, Renhua
Metastasis of lung adenosquamous carcinoma to meningioma: case report with literature review.
The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient's first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules. PMID:24228131
Glass, Ryan; Hukku, Supriya R; Gershenhorn, Bruce; Alzate, Juan; Tan, Bradford
Metastasis of lung adenosquamous carcinoma to meningioma: case report with literature review
The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient�s first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules.
Glass, Ryan; Hukku, Supriya R; Gershenhorn, Bruce; Alzate, Juan; Tan, Bradford
Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma
Background Adenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mutations in a cohort of 30 adenosquamous carcinomas of the uterine cervix. Methods EGFR, PDGFRA and VEGFR2 immunohistochemistry was performed in all samples, followed by DNA isolation from the gross macroscopically dissection of the neoplastic area. Screening for EGFR (exons 18�21) and PDGFRA (exons 12, 14 and 18) mutations was done by PCR � single-strand conformational polymorphism (PCR-SSCP). Results Despite the presence of EGFR immunohistochemical positive reactions in 43% (13/30) of the samples, no EGFR activating mutations in the hotspot region (exons 18�21) were identified. A silent base substitution (CAG>CAA) in EGFR exon 20 at codon 787 (Q787Q) was found in 17 cases (56%). All PDGFRA immunohistochemical reactions were positive and consistently observed in the stromal component, staining fibroblasts and endothelial cells, as well as in the cytoplasm of malignant cells. No activating PDGFRA mutations were found, yet, several silent mutations were observed, such as a base substitution in exon 12 (CCA>CCG) at codon 567 (P567P) in 9 cases and in exon 18 (GTC>GTT) at codon 824 (V824V) in 4 cases. We also observed the presence of base substitutions in intron 14 (IVS14+3G>A and IVS14+49G>A) in two different cases, and in intron 18 (IVS18-50insA) in 4 cases. VEGFR2 positivity was observed in 22 of 30 cases (73.3%), and was significantly associated with lack of metastasis (p = 0.038). Conclusion This is the most extensive analysis of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinomas. Despite the absence of EGFR and PDGFRA activating mutations, the presence of overexpression of these three important therapeutic targets in a subset of cases may be important in predicting the sensitivity of adenosquamous carcinoma to specific anti-RTKs drugs.
Pancreatitis Associated with Pancreatic Carcinoma
The combined occurrence of pancreatic carcinoma with acute or chronic pancreatitis is seldom seen in medical practice, but when present it is a challenging dilemma, plagued by confusing overlapping clinical findings and pitfalls in diagnostic imaging tests. This article reviews the presumptive pathophysiological aspects of this relationship, the perplexing clinical presentations and the advantages and limitations of the noninvasive imaging
E. J. Balthazar
Durable Response of Human Epidermal Growth Factor Receptor-2-Positive Gastric Adenosquamous Carcinoma to Trastuzumab-Based Chemotherapy
Here, we report a patient with gastric adenosquamous carcinoma (ASC) with human epidermal growth factor receptor-2 (HER2) overexpression who was successfully treated with trastuzumab-based chemotherapy. The patient was a 66-year-old man preoperatively diagnosed with gastric adenocarcinoma with no evidence of distant metastases. On histopathological examination, the curatively resected tumor was identified as ASC with mixed adenocarcinoma and squamous cell carcinoma components. Multiple liver metastases developed 2.5 months after surgery. Because immunohistochemical staining for HER2 was strong in both components, combination chemotherapy with capecitabine, cisplatin, and trastuzumab was initiated. A partial response was confirmed after 6 treatment cycles and PET and CT scans performed after 13 cycles revealed disease resolution with no uptake in the metastatic lesions. No evidence of disease progression has been observed 16 months after initial chemotherapy. This report suggests the potential utility of trastuzumab-based chemotherapy for HER2-positive gastric ASC.
Kadowaki, Shigenori; Yatabe, Yasushi; Nitta, Sohei; Ito, Yuichi; Muro, Kei
Clinical Behaviors and Outcomes for Adenocarcinoma or Adenosquamous Carcinoma of Cervix Treated by Radical Hysterectomy and Adjuvant Radiotherapy or Chemoradiotherapy
Purpose: To compare clinical behaviors and treatment outcomes between patients with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods and Materials: A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and 116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The indications for RT/CCRT were deep stromal invasion, positive resection margin, parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with presence of parametrial invasion or LN metastasis were stratified into a high-risk group, and the rest into an intermediate-risk group. The patterns of failure and factors influencing survival were evaluated. Results: The treatment failed in 39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p = 0.000). Distant metastasis was the major failure pattern in both groups. After multivariate analysis, prognostic factors for local recurrence included younger age, parametrial invasion, AC/ASC histology, and positive resection margin; for distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC histology. Compared with SCC patients, those with AC/ASC had higher local relapse rates for the intermediate-risk group but a higher distant metastasis rate for the high-risk group. Postoperative CCRT tended to improve survival for intermediate-risk but not for high-risk AC/ASC patients. Conclusions: Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for cervical cancer patients treated by RH and postoperative RT. Concurrent chemoradiotherapy could improve survival for intermediate-risk, but not necessarily high-risk, AC/ASC patients.
Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China) [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China); Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China)] [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Lee, Steve P. [Department of Radiation Oncology, University of California, Los Angeles School of Medicine, Los Angeles, CA (United States)] [Department of Radiation Oncology, University of California, Los Angeles School of Medicine, Los Angeles, CA (United States); Hong, Ji-Hong, E-mail: email@example.com [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China) [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China)
Long-Term Outcome and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinoma of Cervix After Definitive Radiotherapy
Purpose: To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery. Methods and Materials: A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed. Results: The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease. Conclusion: Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease.
Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng [Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China); Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Hsueh, Swei [Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Chen, Chien-Kuang [Department of Emergency, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lee, Steve P. [Department of Radiation Oncology, University of California, Los Angeles, School of Medicine, Los, Angeles, CA (United States); Hong, Ji-Hong, E-mail: email@example.com [Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China)
TSG101 and PEG10 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder
The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) are currently not well documented, and as the prevalence of SC/ASC is uncommon in gallbladder cancers, a prognostic marker has not yet been found. In the present study, the expression of tumor susceptibility gene (TSG) 101 and paternally expressed gene (PEG) 10 was assessed in 46 SC/ASCs and 80 adenocarcinomas (ACs) using immunohistochemistry, and the samples were further analyzed to examine correlations with the clinicopathological characteristics. It was demonstrated that positive TSG101 and PEG10 expression were significantly associated with large tumor size, high tumor-node-metastasis (TNM) stage, lymph node metastasis, invasion and no resection (only biopsy) of SC/ASC and AC. The univariate Kaplan-Meier analysis showed that positive TSG101 and PEG10 expression, and differentiation, tumor size, TNM stage, lymph node metastasis, invasion and surgical curability, is closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.001). The multivariate Cox regression analysis identified that positive TSG101 and PEG10 expression are independent factors for a poor-prognosis in SC/ASC and AC patients. The present study indicates that positive TSG101 and PEG10 expression are closely associated with the clinical, pathological and biological behaviors, and a poor prognosis in gallbladder cancer.
UCSD scientists find gene mutation for aggressive form of pancreatic cancer
Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma tumors � the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer.
Primary carcinoid tumor of the uterine cervix presenting as an adenosquamous carcinoma. The importance of electron microscopy and immunohistochemistry in evaluating poorly differentiated cervical neoplasms.
Primary carcinoid tumors of the uterine cervix are uncommon gynecologic neoplasms. An unusual case of this neoplasm is presented that was originally diagnosed as a poorly differentiated adenosquamous cervical carcinoma. A subsequent metastatic pulmonary nodule was discovered 13 months later with the unexpected histologic and ultrastructural features of a carcinoid tumor. The primary cervical malignancy was reassessed ultrastructurally and the original diagnosis was changed to that of a poorly differentiated carcinoid tumor. By using immunoperoxidase techniques, it was observed that serotonin granules were present in the neoplastic cells of the lung and cervix, confirming the carcinoid nature of the tumor. This case differs from the majority of those reported as poorly differentiated cervical carcinoids in that it did not resemble an undifferentiated small cell (oat cell) carcinoma, but was more typical of an adenosquamous carcinoma. This case supports the role of electron microscopy and immunohistochemistry in the complete evaluation and diagnosis of less-differentiated cervical neoplasms in order to specifically identify the primary cell (cells) of origin. Only in this way can one definitively support the diagnosis of a primary carcinoid tumor and perhaps, with this knowledge, the clinicobiologic behavior of this cancer can be altered and possibly improved by initiating different or adjunctive treatment modalities. PMID:6762290
Miles, P A; Herrera, G A; Greenberg, H; Rawding-Patterson, G
Low-Grade Adenosquamous Carcinoma of the Breast with Diverse Expression Patterns of Myoepithelial Cell Markers on Immunohistochemistry: A Case Study
This paper reports a case of low-grade adenosquamous carcinoma (LGASC) arising in a 69-year-old woman, who presented with a 1-cm palpable mass on her right breast. Core needle biopsy diagnosed the mass as a fibroadenoma. After six months, the mass increased in size, and the patient received subsequent mammotome excision. On microscopic examination, bland-looking small glands were infiltrating into the fibrotic stroma with lymphocytic infiltrates at the periphery. Hematoxylin and eosin staining revealed relatively easily detectable myoepithelial cells along the outside in each of the glandular structures with variable degrees of squamous metaplasia. Based on histologic features, the patient was diagnosed with LGASC. LGASC is a rare variant of metaplastic carcinoma, which is characterized by a favorable prognosis. Due to the bland cytology and presence of myoepithelial cells, LGASC can be misdiagnosed as benign lesion. Additionally, inconsistent expression of myoepithelial markers could aid the diagnosis of LGASC.
Cha, Yoon Jin; Kim, Gi Jeong; Park, Byeong-Woo
Diagnostic and Prognostic Biomarkers in Pancreatic Carcinoma
Pancreatic ductal carcinoma, one of the leading causes of cancer mortality, is typically diagnosed at an advanced stage, which significantly contributes to its high mortality rates. Studies have demonstrated that resection of small pancreatic tumors and tumors at lower stages correlates with improved survival. Detection of pancreatic carcinoma at an early, surgically resectable stage is the key to decreasing mortality and improving survival. Identification of sensitive diagnostic biomarkers as screening tools is crucial in detecting preinvasive pancreatic neoplasms. Numerous new DNA-, RNA- and protein-based biomarkers have been extensively investigated. This review aims to provide an update on these molecular markers, including biomarkers from blood, tissue as well as pancreatic juice and cystic fluid. These biomarkers hold potential utility in early diagnosis and prognostification of pancreatic ductal carcinoma, though many of which need to be validated in large-scale prospective studies before they can be used in clinical settings.
Liang, John J.; Kimchi, Eric T.; Staveley-O'Carroll, Kevin F.; Tan, Dongfeng
[(Diagnosis of pancreatitis and pancreatic carcinoma by means of intraoperative fine needle aspiration biopsy)].
Intraoperative fine needle aspiration biopsies were performed in 69 patients with clinical suspicion of pancreatic carcinoma. The biopsies were positive in 20 to 25 patients with proven pancreatic carcinoma. The cytologic appearances and the cellular components of pancreatic carcinoma and pancreatitis are presented and illustrated. PMID:398015
Fladerer, H P
Isolation of Cancer Stem Like Cells from Human Adenosquamous Carcinoma of the Lung Supports a Monoclonal Origin from a Multipotential Tissue Stem Cell
There is increasing evidence that many solid tumors are hierarchically organized with the bulk tumor cells having limited replication potential, but are sustained by a stem-like cell that perpetuates the tumor. These cancer stem cells have been hypothesized to originate from transformation of adult tissue stem cells, or through re-acquisition of stem-like properties by progenitor cells. Adenosquamous carcinoma (ASC) is an aggressive type of lung cancer that contains a mixture of cells with squamous (cytokeratin 5+) and adenocarcinoma (cytokeratin 7+) phenotypes. The origin of these mixtures is unclear as squamous carcinomas are thought to arise from basal cells in the upper respiratory tract while adenocarcinomas are believed to form from stem cells in the bronchial alveolar junction. We have isolated and characterized cancer stem-like populations from ASC through application of selective defined culture medium initially used to grow human lung stem cells. Homogeneous cells selected from ASC tumor specimens were stably expanded in vitro. Primary xenografts and metastatic lesions derived from these cells in NSG mice fully recapitulate both the adenocarcinoma and squamous features of the patient tumor. Interestingly, while the CSLC all co-expressed cytokeratins 5 and 7, most xenograft cells expressed either one, or neither, with <10% remaining double positive. We also demonstrated the potential of the CSLC to differentiate to multi-lineage structures with branching lung morphology expressing bronchial, alveolar and neuroendocrine markers in vitro. Taken together the properties of these ASC-derived CSLC suggests that ASC may arise from a primitive lung stem cell distinct from the bronchial-alveolar or basal stem cells.
Mather, Jennie P.; Roberts, Penelope E.; Pan, Zhuangyu; Chen, Francine; Hooley, Jeffrey; Young, Peter; Xu, Xiaolin; Smith, Douglas H.; Easton, Ann; Li, Panjing; Bonvini, Ezio; Koenig, Scott; Moore, Paul A.
Minute pancreatic carcinoma with initial symptom of acute pancreatitis.
We experienced a case of minute pancreatic carcinoma in a 59-year-old man who complained of upper abdominal pain after drinking alcohol. Abdominal ultrasonography (US) revealed dilatation of the main pancreatic duct (MPD). Abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed slight dilatation of the MPD and its obstruction near the portal vein. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated occlusion of the MPD, and cytology of aspirated pancreatic juice was negative for malignancy. With the diagnosis of benign localized obstruction of the MPD, the patient underwent surgery. There was a clear demarcation of hardness and color of the pancreas on the left margin of the superior mesenteric vein, and the caudal pancreas was hard and fibrotic. Intraoperative US revealed slight dilatation of the MPD, and the aspiration cytology result was class IV. First, segmental resection of the pancreas was performed, but pathological examination of frozen section showed neither malignancy nor stenotic lesion. An additional small portion of the proximal pancreas was resected. The specimen included a ductal carcinoma, 5 mm in diameter. Accordingly, a pylorus-preserving pancreatoduodenectomy was performed. Microscopically, the minute carcinoma had already penetrated the duct wall and infiltrated lymph vessels and veins. The patient has been under close observation at our outpatient clinic, and so far there have been no signs of recurrence. To improve the poor prognosis of pancreatic cancer, we should be alert to the occurrence of acute pancreatitis as an initial symptom. PMID:12541052
Imamura, Mikio; Asahi, Shuji; Yamauchi, Hidemi; Tadokoro, Keiichi; Suzuki, Hiroyoshi
Etiology and oncogenesis of pancreatic carcinoma.
Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis. PMID:23213974
Dobrila-Dintinjana, Renata; Vanis, Nenad; Dintinjana, Marijan; Radi?, Mladen
Spontaneous Adenosquamous Carcinoma with Rapid Growth and EMT-like Changes in the Mammary Gland of a Young Adult Female BALB/c Mouse
This study histopathologically and immunohistochemically investigated a spontaneously occurring single mass subcutaneously located in the left lower abdomen of a female BALB/cAJcl?nu/+ mouse at 10 weeks of age. The mass was about 20 � 15 � 10 mm in size after formalin fixation; nevertheless, it was not detected by clinical observations at 9 weeks of age. H&E staining revealed the tumor origin was epithelial and probably arose from the mammary gland, and the tumor cells demonstrated a squamous, acinar or polyhedral/basal pattern. A cell kinetics analysis revealed that many of the tumor cells of the squamous, acinar or polyhedral/basal component were positive for PCNA and cyclin D1, although there were a few of TUNEL-positive tumor cells in all of the components. An epithelial/mesenchymal analysis demonstrated that most of the tumor cells of the squamous and acinar components contained keratin and E-cadherin; however, most of the tumor cells of the polyhedral/basal component were less or very weakly positive for these markers. The tumor cells of the squamous component were negative for vimentin and SMA; however, many of the tumor cells of the polyhedral/basal component exhibited vimentin. In addition, expression of SMA was confirmed in some tumor cells of the acinar and basal components. Based on the microscopic and immunohistochemical characterizations, the tumor was diagnosed to be adenosquamous carcinoma that originated from the mammary gland with rapid growth, and the tumor cells demonstrated epithelial-mesenchymal transition-like changes.
Takaba, Katsumi; Imada, Teruyoshi; Katsumata, Shigehisa; Okumura, Hiroshi; Iwamoto, Sachiko; Suzuki, Yui; Imaizumi, Minami; Myojo, Kensuke; Takada, Chie; Kimoto, Naoya; Saeki, Koji; Yamaguchi, Itaru
Diagnostic value of serum pancreatic tissue carcinoma antigen in pancreatic carcinoma
Serum pancreatic tissue carcinoma antigen (PCA) was measured by ELISA in 396 patients with pancreatic carcinoma (PC) and other\\u000a diseases diagnosed by clinical examination, histopathology and operation. Serum PCA more than 300 U\\/ml was considered as diagnostic\\u000a value for PC and 30�299 U\\/ml as probable index for PC. The sensitivity of PCA for PC was 78.2% (43\\/55), and the specifity
Jiming Meng; Guoming Xu; Qian Shen; Hongfu Zhang; Yueqin Wu; Guangbi Yao
Target therapies in pancreatic carcinoma.
Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early locoregional spread and distant metastases at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provides only modest benefit to patients with PDAC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies (monoclonal antibodies and small-molecule inhibitors) and peculiar new class of taxanes with a crucial therapeutic role in this cancer setting. A phase III trial has shown that erlotinib in combination with gemcitabine was clinically irrelevant and skin toxicity can be a positive prognostic factor. Moreover, the combination of cetuximab or erlotinib with radiotherapy in advanced pancreatic cancer has shown to be synergistic and a reversal of radio-resistance has been suggested by inhibition of VEGF/EGFR pathway. To overcome EGFR-inhibition therapy resistance several alternative pathways targets are under investigation (IGF- 1R, MMPs, Hedgehog proteins, m-TOR, MEK, COX-2) and provide the rationale for clinical use in phase II/III studies. Also nab-paclitaxel, a new taxanes class, uses high pancreatic albumin-binding protein SPARC levels to act in cancer cells with a less toxic and more effective dose with respect to classic taxanes. Understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. However, many promising data in preclinic and phase I/II trials did not yield promise in phase III trials, suggesting that identification of predictive biomarkers for these new agents is mandatory. The knowledge of biologic and molecular aspects of pancreatic cancer can be the basis for future therapeutic developments. PMID:23992319
Silvestris, Nicola; Gnoni, Antonio; Brunetti, Anna Elisabetta; Vincenti, Leonardo; Santini, Daniele; Tonini, Giuseppe; Merchionne, Francesca; Maiello, Evaristo; Lorusso, Vito; Nardulli, Patrizia; Azzariti, Amalia; Reni, Michele
Genetic alterations in pancreatic carcinoma
Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is
Gunter Schneider; Roland M Schmid
The role of radiotherapy in multimodal treatment of pancreatic carcinoma
Pancreatic ductal carcinoma is one of the most lethal malignancies, but in recent years a number of positive developments have occurred in the management of pancreatic carcinoma. This article aims to give an overview of the current knowledge regarding the role of radiotherapy in the treatment of pancreatic ductal adenocarcinoma (PDAC). The results of meta-analyses, phase III-studies, and phase II-studies
Thomas B Brunner; Martin Scott-Brown
Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma
In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated.
Gerloff, Andreas; Singer, Manfred V; Feick, Peter
Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis: Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging
AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-I, II, III, and IV, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-III (n = 13) or IV (n = 20) TIC. Tumor-forming pancreatitis showed type-II (n = 5) or III (n = 3) TIC. All islet cell tumors revealed type-I. The type-IV TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis. CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.
Tajima, Yoshitsugu; Kuroki, Tamotsu; Tsutsumi, Ryuji; Isomoto, Ichiro; Uetani, Masataka; Kanematsu, Takashi
Characterization and utilization of a monoclonal antibody against pancreatic carcinoma.
National Technical Information Service (NTIS)
A monoclonal antibody was produced against a human pancreatic adenocarcinoma line and was found to react with several different human carcinomas by immunoperoxidase staining of fixed tissues. The original cells used to generate the monoclonal antibody wer...
S. H. Kurtzman W. F. Sindelar R. W. Atcher J. B. Mitchell W. G. DeGraff
Prognostic Parameters Determining Survival in Pancreatic Carcinoma and, in Particular, after Palliative Treatment
Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients
Karsten Ridwelski; Frank Meyer; Matthias Ebert; Peter Malfertheiner; Hans Lippert
Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy: A case report
Pancreatic tuberculosis (TB) is a rare condition, even in immunocompetent hosts. A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient. The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice. Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma. The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy. A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits. The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy. A biopsy of the pancreas and lymph nodes was performed, revealing TB infection. The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo. This case is reported to emphasize the rare contribution of pancreatic TB to pancreatic masses and obstructive jaundice.
Yang, Yan-Jia; Li, Ya-Xin; Liu, Xiao-Qin; Yang, Mei; Liu, Kai
Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma.
In this study, two cases of biopsy-proven pancreatic tuberculosis are reported. The patients presented with fever, anorexia, fatigue, abdominal pain and weight loss. A differential diagnosis of fever of unknown origin was conducted. Computed tomography (CT) revealed a cystic mass image in the pancreatic head in one patient, and a hypodense lesion in the pancreatic head in the other. The first patient was diagnosed by a wedge biopsy specimen obtained in the exploratory laparotomy. The other patient was diagnosed by percutaneous fine-needle aspiration biopsy. Both patients were successfully treated with quadruple antituberculous therapy for 12 months. We concluded that especially in young patients who present with a mass in the pancreas, pancreatic tuberculosis should be considered among the differential diagnoses, particularly in developing countries and immunosuppressed individuals. PMID:11595077
Demir, K; Kaymakoglu, S; Besisik, F; Durakoglu, Z; Ozdil, S; Kaplan, Y; Boztas, G; Cakaloglu, Y; Okten, A
[Surgical technique and outcome in pancreatic carcinoma].
Surgical treatment of ductal adenocarcinoma of the pancreas is considerably influenced by the delicate retroperitoneal position of the gland with close contact to major mesenteric vessels, lymphatics and nerve structures as well as by the unfavourable tumor biology including high affinity towards nerve tissue and early systemic spread. Based on these preconditions, kind and extent of resective measures have to be discussed with special care. Total pancreatectomy to improve radicality has been abandoned because of exaggerated early and late mortality and morbidity. The principle of distal gastric resection as part of the classic Whipple operation was shown to be oncologically not effective. It seems to be justified only if the tumor reaches the duodenopancreatic angle. Resection of the mesenteric vein is technically feasible with acceptable mortality, but leads to unfavourable survival rates since the respective lesions mostly are in an advanced stage. Extensive tissue clearance around the mesenteric vessels did not improve survival, but led to intractable diarrhoea in up to 76% of the cases. Concerning 114 patients resected for pancreatic head cancer in the own department actuarial 5-year survival was 6%. There was no significant difference whether classic Whipple (3%) or pylorus preservation (8%) was applied. None of the node positive patients survived more than 4 years. In contrast, those with negative nodes achieved 29% 5-years survival (p = 0.0059). Following 26 resections of the left pancreas for ductal carcinoma non of the patients survived more than 2 years. Results of the recent literature and the own experience are suggestive to believe that node positive stages won't benefit from extensive surgery. Therefore anatomical resection including the peripancreatic lymph node compartment is sufficient to preserve the chance for cure in early stages. Nowadays preservation of the stomach is the standard technique during pancreatoduodenectomy, which is, provided a perioperative mortality of less than 5%, accepted also as best palliation in suitable patient of advanced stages. PMID:11142139
Heise, J W
Functional Pancreatic Acinar Cell Carcinoma Extending into the Main Pancreatic Duct and Splenic Vein
Introduction��Pancreatic acinar cell carcinoma (ACC) has several unique characteristics, such as its progression pattern, spreading into\\u000a the pancreatic duct and large blood vessels, and its secretion of pancreatic exocrine enzymes, which induces a paraneoplastic\\u000a syndrome.\\u000a \\u000a \\u000a \\u000a \\u000a Case Report��A 79-year-old Japanese man, with medical history of chronic renal failure, was referred to our institution for the examination\\u000a of his abdominal pain and
Mineo Iwatate; Hiroyuki Matsubayashi; Keiko Sasaki; Naoki Kishida; Shusuke Yoshikawa; Hiroyuki Ono; Anirban Maitra
Anti-Angiogenesis Therapy in Pancreatic Carcinoma
Summary Pancreatic adenocarcinoma is a leading cause of cancer death in the United States and represents a challenging chemotherapeutic problem. The treatment of advanced pancreatic cancer with gemcitabine has only modest activity with a small survival benefit, and toxicity continues to be a major obstacle. New therapeutic strategies that notably lack cross resistance with established treatment regimens are much needed
Muhammad Wasif Saif
Pancreatic carcinoma in fibrocalcific pancreatic diabetes: An eastern India perspective.
Fibrocalcific pancreatic diabetes (FCPD) is a rare cause of diabetes (<1%) of uncertain etiology associated with >100-fold increased risk of pancreatic cancer. We present 3 patients of FCPD with pancreatic cancer who had long duration of diabetes (19 years, 25 years, and 28 years, respectively), all of whom presented with anorexia, weight loss, and worsened glycemic control. Patient-1 in addition presented with deep venous thrombosis. All the 3 patients had evidence of metastasis at the time of diagnosis. Computerized tomography (CT) abdomen revealed atrophic pancreas, dilated pancreatic ducts, and multiple calculi in the head, body, and tail of pancreas in all of them. Patient-1 had 38 mm � 38 mm � 32 mm mass in the tail of pancreas with multiple target lesions were seen in the right lobe of liver. Patient-2 had a mass in the tail of pancreas (46 � 34 � 31 mm) encasing the celiac plexus and superior mesenteric artery infiltrating the splenic hilum and splenic flexure of colon. Patient-3 also had a mass in the tail of pancreas (33 � 31 � 22 mm), with multiple target lesions in the liver, suggestive of metastasis. All patients had elevated serum CA19-9 (828.8, 179.65, and 232 U/L, respectively; normal <40 U/L). Patients of FCPD with anorexia, weight loss, worsening of glycemic control should be evaluated to rule out pancreatic cancer. Studies are warranted to evaluate CA19-9 as a screening tool for diagnosing pancreatic cancer at an earlier stage in FCPD. PMID:23565475
Chakraborty, Partha Pratim; Dutta, Deep; Biswas, Kaushik; Sanyal, Triranjan; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar
Epidermal Growth Factor Receptor Expression in Pancreatic Carcinoma Using Tissue Microarray Technique
Background: The effect of overexpression of epidermal growth factor receptor (EGFR) in pancreatic carcinoma is not clear. Utilizing tissue microarrays, we evaluated EGFR expression in pancreatic cancer to determine the association of EGFR expression with histopathologic characteristics and patient outcome. Methods: 71 cases of pancreatic adenocarcinoma and 18 cases of chronic pancreatitis were retrieved from archival files. Tissue cores from
Mark Bloomston; Atul Bhardwaj; E. Christopher Ellison; Wendy L. Frankel
Androgen receptor signaling in hepatocellular carcinoma and pancreatic cancers
Hepatocellular carcinoma (HCC) and pancreatic cancer remain difficult to treat, and despite the ongoing development of new treatments, the overall survival rate has only modestly improved over the past decade. Liver and pancreatic progenitors commonly develop from endoderm cells in the embryonic foregut. A previous study showed that HCC and pancreatic cancer cell lines variably express androgen receptor (AR), and these cancers and the surrounding tissues also express AR. AR is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily. Androgen response element is present in regulatory elements on the AR-responsive target genes, such as transforming growth factor beta-1 (TGF beta-1) and vascular endothelial growth factor (VEGF). It is well known that the activation of AR is associated with human carcinogenesis in prostate cancer as well as HCC and pancreatic cancer and that GRP78, TGF beta, and VEGF all play important roles in carcinogenesis and cancer development in these cancers. HCC is a male-dominant cancer irrespective of its etiology. Previous work has reported that vertebrae forkhead box A 1/2 are involved in estrogen receptors and/or AR signaling pathways, which may contribute to the gender differences observed with HCC. Our recent work also showed that AR has a critical role in pancreatic cancer development, despite pancreatic cancer not being a male dominant cancer. Aryl hydrocarbon (or dioxin) receptor is also involved in both HCC and pancreatic cancer through the formation of complex with AR. It is possible that AR might be involved in their carcinogenesis through major histocompatibility complex class?I?chain-related gene A/B. This review article describes AR and its role in HCC and pancreatic cancer and suggests that more specific AR signaling-inhibitors may be useful in the treatment of these �difficult to treat� cancers.
Kanda, Tatsuo; Jiang, Xia; Yokosuka, Osamu
Photodynamic therapy for pancreatic and biliary tract carcinoma
NASA Astrophysics Data System (ADS)
Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.
Pereira, Stephen P.
[Histogenetic classification of exocrine pancreatic carcinomas].
The structures of normal ductal and ductular epithelium were compared with cytological peculiarities of pancreas carcinoma. This provided the basis on which to propose histogenetic classification of exocrine pancreas carcinoma. Most of the pancreas carcinomas are adenocarcinomas and originate from small lateral ductules. Preneoplastic ductal alterations, such as proliferation of ductal epithelium, adenomatous dysplasia, and light-cell transformation, may be topographically distinguished from ductular changes, including centroacinic hyperplasia, oncocytic transformation, microglandular metaplasia, ductulo-acinic metaplasia, hepatocellular metaplasia, and peri-insular metaplasia. The close correlations that exist between ductular and acinic cells may be summarised under the cover term of terminal ductulo-acinic intercalated duct complex. Dysplasia is generally accompanied by decline in neutral glycosaminoglycans and occurrence of unsubstituted sialomucin of the embryonic type. PMID:2781881
Schulz, H J
Detection of the pancreas-specific gene in the peripheral blood of patients with pancreatic carcinoma.
The prognosis of patients with pancreatic carcinoma remains very poor. To improve the therapeutic results, the early detection of this cancer is needed. The present study was performed to detect the pancreas-specific gene, chymotrypsinogen, in the peripheral blood from patients with pancreatic carcinoma by using reverse transcription polymerase chain reaction (RT-PCR) in order to evaluate the clinical significance of this gene. Ten patients with pancreatic carcinoma, two with acute pancreatitis, three with chronic pancreatitis and ten control subjects were examined for the presence of chymotrypsinogen using RT-PCR techniques in the peripheral blood. To confirm that the chymotrypsinogen gene was expressed in a pancreas-specific manner, the expression of chymotrypsinogen in various types of human adult tissue was evaluated by RT-PCR. The specific band of the chymotrypsinogen gene was detected in the pancreas. Serial dilution studies demonstrated the chymotrypsinogen gene to be detected at a concentration of one pancreatic cell per 10(6) peripheral blood cells. Seven out of the ten (70%) patients with pancreatic carcinoma were found to be positive based on the RT-PCR findings. In contrast, no pancreas-specific gene was detected in the peripheral blood of any patients with acute pancreatitis, chronic pancreatitis or the control subjects. Our observations show that the detection of the pancreatic specific gene, chymotrypsinogen, is therefore useful as a genetic diagnostic marker in pancreatic carcinoma. PMID:10496364
Kuroki, T; Tomioka, T; Tajima, Y; Inoue, K; Ikematsu, Y; Ichinose, K; Furui, J; Kanematsu, T
Detection of the pancreas-specific gene in the peripheral blood of patients with pancreatic carcinoma
The prognosis of patients with pancreatic carcinoma remains very poor. To improve the therapeutic results, the early detection of this cancer is needed. The present study was performed to detect the pancreas-specific gene, chymotrypsinogen, in the peripheral blood from patients with pancreatic carcinoma by using reverse transcription polymerase chain reaction (RT-PCR) in order to evaluate the clinical significance of this gene. Ten patients with pancreatic carcinoma, two with acute pancreatitis, three with chronic pancreatitis and ten control subjects were examined for the presence of chymotrypsinogen using RT-PCR techniques in the peripheral blood. To confirm that the chymotrypsinogen gene was expressed in a pancreas-specific manner, the expression of chymotrypsinogen in various types of human adult tissue was evaluated by RT-PCR. The specific band of the chymotrypsinogen gene was detected in the pancreas. Serial dilution studies demonstrated the chymotrypsinogen gene to be detected at a concentration of one pancreatic cell per 106 peripheral blood cells. Seven out of the ten (70%) patients with pancreatic carcinoma were found to be positive based on the RT-PCR findings. In contrast, no pancreas-specific gene was detected in the peripheral blood of any patients with acute pancreatitis, chronic pancreatitis or the control subjects. Our observations show that the detection of the pancreatic specific gene, chymotrypsinogen, is therefore useful as a genetic diagnostic marker in pancreatic carcinoma. � 1999 Cancer Research Campaign
Kuroki, T; Tomioka, T; Tajima, Y; Inoue, K; Ikematsu, Y; Ichinose, K; Furui, J; Kanematsu, T
Refractory Gastroesophageal Variceal Bleeding Secondary to Neuroendocrine Carcinoma in the Pancreatic Tail
The main cause of gastroesophageal variceal bleeding (GEVB) is portal hypertension (PH) due to liver cirrhosis. Here, we report a case of regional PH and refractory GEVB secondary to neuroendocrine carcinoma (NC) in the pancreatic tail. This condition was treated using a pancreatic tail resection, splenectomy, and portal azygous devascularization. Regional PH caused by a pancreatic NC is rare and
Huaizhi Wang; Ping Bie; Leida Zhang
Detection of HBs-Ag in the pancreas in cases of pancreatic carcinoma.
Detection of HBs-Ag in the pancreatic juice in acute and chronic hepatic failure caused by hepatitis-B-infection leads to the assumption that parts of that virus are produced by the pancreas. We investigated pancreatic tissue obtained during Whipple's procedure in 51 cases of pancreatic carcinoma. In 5 specimens HBs-Ag was detected, mostly located in acinar cells and inside small ducts. In view of our knowledge of the carcinogenesis of human hepatocellular carcinoma, hepatitis B virus could produce an oncogenic effect in pancreatic carcinoma, too. PMID:6510882
Hohenberger, P
Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma
Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5-overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil.
Hagmann, Wolfgang; Faissner, Ralf; Schnolzer, Martina; Lohr, Matthias; Jesnowski, Ralf
Pancreatic Panniculitis in an 88YearOld Man with Neuroendocrine Carcinoma
Pancreatic panniculitis is a rare complication that occurs in 0.3�3% of patients with pancreatic diseases. Most of the cases reported to date were associated with adenocarcinoma and acute or chronic pancreatitis. We here present an 88-year-old man who was admitted to our institution with a nonfunctional neuroendocrine carcinoma of the pancreas. He subsequently developed pancreatic panniculitis and arthritis. Treatment with
Jan Christian Preiss; Siegbert Faiss; Christoph Loddenkemper; Martin Zeitz; Rainer Duchmann
[Efficacy of neoadjuvant chemotherapy for resectable pancreatic carcinoma].
Surgery followed by adjuvant chemotherapy is standard care for resectable pancreatic carcinoma. The maximum estimated 2-year survival rate associated with this strategy is nearly 50%. The use of neoadjuvant therapy for pancreatic cancer remains controversial, and its efficacy has not been elucidated. To evaluate the efficacy of neoadjuvant chemotherapy for planned pancreatic cancer resection, the oncological outcomes of neoadjuvant gemcitabine plus S-1 combination therapy( GS therapy) and a surgery-first approach were retrospectively compared. Patients with planned pancreatic cancer resection and without major artery abutments were enrolled in this study. There were 39 cases of neoadjuvant GS therapy (N group) and 93 cases of the surgery-first approach( S group). Survival and surrogate markers, including the R0 rate, the "true R0 rate"( R0 with tumor marker normalization after resection), and N0 rate, were compared. The groups did not differ significantly in terms of age, gender, or tumor location. The resection rates of the N and S groups were similar (92% and 86%, respectively). The median survival of the N group (39.4 months) was significantly longer than that of the S group (20.8 months) in intention-to-treat analysis (p=0.0009). The R0, true R0, and N0 rates of the N group (85%, 69%, and 44%, respectively) were higher than those of the S group( 72%, 48%, and 24%, respectively). In conclusion, this retrospective analysis showed that neoadjuvant GS therapy might be more effective than the standard surgery-first strategy in terms of oncological outcomes for resectable pancreatic cancer. A prospective randomized study, Prep-02/JSAP-05, which compares neoadjuvant therapy to the surgery-first approach, is ongoing (UMIN-No. 000009634). PMID:24393872
Motoi, Fuyuhiko; Kawaguchi, Kei; Aoki, Takeshi; Kudo, Katsumasa; Yabuuchi, Shinichi; Fukase, Koji; Mizuma, Masamichi; Sakata, Naoaki; Otsutomo, Shigeru; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Okada, Takaho; Yoshida, Hiroshi; Naitoh, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki
[The diagnosis of pancreatic carcinoma by combined endoscopic retrograde pancreatiography, aspiration cytology and carcinoembryonic antigen determination in the pancreatic secretion (author's transl)].
The reliability of diagnostic procedures in pancreatic disease can be significantly increased by the combination of endoscopic retrograde pancreaticography, determination of carcinoembryonic antigen and cytological examination of the aspirated pancreatic section. In the present study all cases of pancreatic carcinoma were correctly diagnosed by these methods. These combined diagnostic procedures seem to provide the basis for potential progress in the diagnosis of pancreatic carcinoma. PMID:654299
Brandst�ter, G; Kratochvil, P; Wiedner, F; Justich, E; Fladerer, H
A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform
There are a large number of stable pancreatic ductal carcinoma cell lines that are used by researchers worldwide. Detailed data about their differentiation status and growth features are, however, often lacking. We therefore attempted to classify commonly used pancreatic carcinoma cell lines according to defined cell biological criteria. Twelve pancreatic ductal adenocarcinoma cell lines were cultured as monolayers and spheroids
Bence Sipos; Simone M�ser; Holger Kalthoff; Virag T�r�k; Matthias L�hr; G�nter Kl�ppel
Multiple MR imaging techniques in the diagnosis and assessment of resectability in pancreatic carcinoma
Objective: To study the value of multiple MR imaging techniques in the diagnosis of pancreatic carcinoma and the assessment of resectbility\\u000a of the lesion.Methods: MR imaging was performed in 18 patients with surgically and\\/or pathologically proven pancreatic carcinoma. GRE T1WI, TSE\\u000a T2WI, GRE T1W1 with fat suppression, delayed enhancement GRE T1WI, MRCP and 3D DCE MRA were used in MR
Long Yu; Kong Xiangquan; Xu Haibo; Liu Dingxi; Yang Fan; Xiong Yin; Yu Qun; Peng Zhenjun
Characterization and utilization of a monoclonal antibody against pancreatic carcinoma
A monoclonal antibody was produced against a human pancreatic adenocarcinoma line and was found to react with several different human carcinomas by immunoperoxidase staining of fixed tissues. The original cells used to generate the monoclonal antibody were treated with detergent to lyse the cell membrane. A membrane associated protein of molecular weight 35kD was isolated from this detergent lysed preparation and found to be recognized by the monoclonal antibody. The binding constant of the antigen antibody reaction on the cells is 5 x 10{sup {minus}5}. It was further determined that there are 700,000 binding sites per cell. Kinetics of the antigen-antibody reaction under several conditions were also explored.
Kurtzman, S.H.; Sindelar, W.F.; Atcher, R.W.; Mitchell, J.B.; DeGraff, W.G.; Gamson, J.; Russo, A. [National Cancer Institute, Bethesda, MD (United States); Friedman, A.M.; Hines, J.J. [Argonne National Lab., IL (United States)
Early lesions of pancreatic ductal carcinoma in the hamster model.
Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system. PMID:195472
Pour, P; Althoff, J; Takahashi, M
Early lesions of pancreatic ductal carcinoma in the hamster model.
Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22
Pour, P.; Althoff, J.; Takahashi, M.
L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma
AIM: To determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. METHODS: We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody UJ127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendocrine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULTS: L1 was detected in 5 (7.9%) of 63 pancreatic neuroendocrine tumors. Four (44.4%) of 9 poorly-differentiated carcinomas expressed L1. In contrast, only 1 (1.9%) of 54 well-differentiated tumors or carcinomas was positive for L1. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas (P<0.01). CONCLUSION: L1 is specifically expressed in poorly-differentiated pancreatic neuroendocrine carcinomas that are known to have the worst prognosis. L1 might be a marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.
Kaifi, Jussuf T; Zinnkann, Ulrich; Yekebas, Emre F; Schurr, Paulus G; Reichelt, Uta; Wachowiak, Robin; Fiegel, Henning C; Petri, Susann; Schachner, Melitta; Izbicki, Jakob R
A case of necrotizing pancreatitis subsequent to transcatheter arterial chemoembolization in a patient with hepatocellular carcinoma
Necrotizing pancreatitis is one of the rare complications of transcatheter arterial chemoembolization (TACE). Necrotizing pancreatitis after TACE may result from the development of ischemia caused by regurgitation of embolic materials into the vessels supplying the pancreas. We report a case of post-TACE necrotizing pancreatitis with abscess formation in a patient with hepatocellular carcinoma. The patient had suffered hepatic artery injury due to repetitive TACE; during his 25th TACE procedure he had submitted to selective catheterization of the feeding vessel from the dorsal pancreatic artery with a cytotoxic agent and Gelfoam particles. The patient complained of abdominal pain after the TACE procedure, and a CT scan led to a diagnosis of necrotizing pancreatitis with abscess formation. The pancreatic abscess progressed despite general management of the pancreatitis, including antibiotics. Percutaneous catheter drainage was performed, and the symptoms of the patient improved.
Bae, Song-I; Lee, Jong Mee; Kim, Ji Hoon; Lee, Hyun Jung; Lee, Sun Jae; Suh, Sang Jun; Yoon, Eileen L.; Kim, Hae Rim; Byun, Kwan Soo; Seo, Tae-Seok
MicroRNA-20a overexpression inhibited proliferation and metastasis of pancreatic carcinoma cells.
The aim of this study was to investigate the effect of microRNA-20a on pancreatic carcinoma cell proliferation and invasion and to find a new effective treatment strategy for pancreatic carcinoma. MicroRNA-20a expression was determined in 10 matched normal pancreatic tissues and pancreatic carcinoma by in situ hybridization. Quantitative real-time RT-PCR was used to evaluate the expression of microRNA-20a in two pancreatic carcinoma cell lines (BxPC-3 and Panc-1) and immortal human pancreatic duct epithelial cell line H6C7. Proliferation and invasion capacity were analyzed for the cells with lentivirus-mediated overexpression of microRNA-20a both in vitro and in vivo. In addition, the regulation of signal transducer and activator of transcription proteins 3 (Stat3) by microRNA-20a was determined to elucidate the underlying mechanisms. The pancreatic cancer cell lines (Panc-1 and BxPC-3) stably overexpressing microRNA-20a showed reduced proliferation and invasion capacity in vitro and in vivo, compared with parental cells or cells transfected with a control vector. Furthermore, we found that microRNA-20a negatively regulated Stat3 protein expression in a dose-dependent manner without changing the Stat3 mRNA level and decreased the activity of a luciferase reporter construct containing the Stat3 3'-untranslated region. These results show that microRNA-20a regulates Stat3 at the post-transcriptional level, resulting in inhibition of cell proliferation and invasion of pancreatic carcinoma. It may open a new perspective for the development of effective gene therapy for pancreatic carcinoma. PMID:20583868
Yan, Haijiao; Wu, Jiangxue; Liu, Wensong; Zuo, Yufang; Chen, Shupeng; Zhang, Shineng; Zeng, Musheng; Huang, Wenlin
Pancreatic head carcinoma and right hepatic artery: embolization management--A case report
A replaced right hepatic artery (RHA) is the most common anatomical variation in pancreatic surgery. The RHA is frequently encountered and can be problematic in pancreatic carcinoma. The preservation of the RHA is necessary to avoid ischemic complications but can impact margins resection in pancreaticoduodenectomy (PD). We report a case of a 53-year-old man with a head pancreatic carcinoma. There was a close contact between the tumor and the RHA arising from superior mesenteric artery (SMA). Preoperative embolization of the RHA was performed prior to PD.
Leteurtre, Emmanuelle; Sergent, Geraldine; Ernst, Olivier; Maunoury, Vincent; Branche, Julien; Pruvot, Francois-Rene; Truant, Stephanie
Comparison of histopathological features of pancreatic carcinoma and type 1 autoimmune pancreatitis.
Type 1 autoimmune pancreatitis (AIP-1) is an immunoglobulin G (IgG)-4-related disease (IgG4-RD), characterized by elevated serum immunoglobulin G4 (IgG4) and infiltration by IgG4(+) plasma cells. Pancreatic carcinoma (PC) sometimes shows infiltration by IgG4(+) plasma cells, but details have been unclear. We compared pathological findings and expression of IgG4 and IgG in fibroses in 18 PC patients to those from 9 AIP-1 patients. Fibroses were divided into areas of ductal adenocarcinoma (DA) and obstructive pancreatitis (OP). Serum IgG4 levels were lower than the cut-off value in all PC patients with no IgG4-RD. Diffuse lymphoplasmacytic infiltration and eosinophil infiltration were characteristic of fibroses in PC. Though AIP-1 samples often had storiform fibrosis even in biopsies, PC did not show storiform fibrosis. Ratios of IgG4(+) plasma cells/IgG(+) plasma cells (IgG4/IgG ratios) in DA and OP were significantly lower than in AIP-1. However, high-density IgG4(+) plasma cell foci were detected in PC fibroses, particularly around peripheral nerves, vessels, and lymphoid follicles; between lobules and invasion fronts; and within neutrophilic abscesses. In conclusion, the IgG4/IgG ratio is useful in distinguishing PC from AIP-1, and should be evaluated in three or more areas, as PC can show localized high-density IgG4(+) plasma cell areas. PMID:24629172
Uehara, Takeshi; Hamano, Hideaki; Kawa, Shigeyuki; Kobayashi, Yukihiro; Yoshizawa, Akihiko; Oki, Keiko; Nakata, Rie; Kobayashi, Akira; Sano, Kenji; Ota, Hiroyoshi
EGFR-dependent pancreatic carcinoma cell metastasis via Rap1 activation
Tyrosine kinase receptors play an essential role in various aspects of tumor progression. In particular, epidermal growth factor receptor (EGFR) and its ligands have been implicated in the growth and dissemination of a wide array of human carcinomas. Here, we describe an EGFR-mediated signaling pathway that regulates human pancreatic carcinoma cell invasion and metastasis, yet does not influence the growth of primary tumors. In fact, ligation/activation of EGFR induces Src-dependent phosphorylation of two critical tyrosine residues of p130CAS, leading to assembly of a CAS/Nck1 complex that promotes Rap1 signaling. Importantly, GTP loading of Rap1 is specifically required for pancreatic carcinoma cell migration on vitronectin, but not on collagen. Furthermore, Rap1 activation is required for EGFR-mediated metastasis in vivo without impacting primary tumor growth. These findings identify a molecular pathway that promotes the invasive/metastatic properties of human pancreatic carcinomas driven by EGFR.
Huang, Miller; Anand, Sudarshan; Murphy, Eric A.; Desgrosellier, Jay S.; Stupack, Dwayne G.; Shattil, Sanford J.; Schlaepfer, David D.; Cheresh, David A.
Metastases From Nested Variant Urothelial Carcinoma of the Urinary Bladder in Pancreatic Allograft Mimicking Graft Rejection
While not an uncommon tumor, urothelial carcinoma of the urinary bladder is rare in bladders draining pancreatic allografts. A case of urothelial carcinoma directly involving a pancreatic allograft with metastasis that occurred in a 49-year-old pancreas and kidney transplant recipient is described. Her initial clinical presentation and findings of CT scan of the abdomen suggested pancreatitis with features worrisome for rejection. A biopsy of her pancreatic allograft contained poorly differentiated carcinoma and cystoscopic biopsy disclosed an invasive high grade urothelial carcinoma arising in the background of extensive urothelial carcinoma in situ. Exploratory laparotomy revealed that the tumor invaded the right ovary and fallopian tube, cecum, and allograft with extensive retroperitoneal involvement. She underwent en bloc resection of distal ileum and cecum, resection of transplant pancreas, partial cystectomy, ileocolostomy anastomosis, and right salpingo-oophorectomy. Postoperatively, the patient was treated with four cycles of carboplatin and gemcitabine. She ultimately succumbed to her disease approximately 1 year after diagnosis. This case should alert physicians and radiologists to be aware of atypical presentation of urothelial carcinoma in bladder-drained pancreas grafts, the aggressiveness of such lesions, and the need for early biopsy to avoid diagnostic confusion with rejection. Keywords Bladder cancer; Nested variant of urothelial carcinoma; Pancreas and kidney transplantation
Wang, Jue; Talmon, Geoffrey; Kazmi, Syed A. Jaffar; Siref, Larry E.; Morris, Michael C.
Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma
Background Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods. Methods Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells) received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo. Results The cleaved poly ADP ribose polymerase (PARP)-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05) and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05). Conclusion Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single gemcitabine therapy. The combination therapy method is a potential treatment method for pancreatic carcinoma.
Gong, Dao-Jun; Zhang, Jia-Min; Yu, Min; Zhuang, Bo; Guo, Qing-Qu
Perspectives of TGF-? inhibition in pancreatic and hepatocellular carcinomas
Advanced pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) are non-curable diseases with a particularly poor prognosis. Over the last decade, research has increasingly focused on the microenvironment surrounding cancer cells, and its role in tumour development and progression. PDAC and HCC differ markedly regarding their pathological features: PDAC are typically stromal-predominant, desmoplastic, poorly vascularized tumours, whereas HCC are cellular and highly vascularized. Despite these very different settings, PDAC and HCC share transforming growth factor-? (TGF-?) as a common key-signalling mediator, involved in epithelial-to-mesenchymal transition, invasion, and stroma-tumour dialogue. Recently, novel drugs blocking the TGF-? pathway have entered clinical evaluation demonstrating activity in patients with advanced PDAC and HCC. TGF-? signalling is complex and mediates both pro- and anti-tumoural activities in cancer cells depending on their context, in space and time, and their microenvironment. In this review we provide a comprehensive overview of the role of the TGF-? pathway and its deregulation in PDAC and HCC development and progression at the cellular and microenvironment levels. We also summarize key preclinical and clinical data on the role of TGF-? as a target for therapeutic intervention in PDAC and HCC, and explore perspectives to optimize TGF-? inhibition therapy
Tijeras-Raballand, Annemilai; de Mestier, Louis; Cros, Jerome; Faivre, Sandrine; Raymond, Eric
Peripancreatic lymph node enlargement in Hodgkin's disease, non-Hodgkin's lymphoma, and pancreatic carcinoma.
The distribution of enlarged lymph nodes in the upper abdomen and retroperitoneum were classified according to their relationship to the pancreas in 47 patients with non-Hodgkin's lymphoma; in nine patients with Hodgkin's disease; and in 40 patients with pancreatic carcinoma. Four patterns of lymph node enlargement were evident: (1) preaortic retropancreatic lymphadenopathy; (2) pancreaticosplenic lymphadenopathy; (3) isolated celiac and/or portal lymphadenopathy; and (4) diffuse extensive lymphadenopathy. Features differentiating lymphoma from primary pancreatic neoplasm are discussed. PMID:6362986
Costello, P; Duszlak, E J; Kane, R A; Lee, R G; Clouse, M E
The expression and functions of microRNAs in pancreatic adenocarcinoma and hepatocellular carcinoma
Pancreatic adenocarcinoma and hepatocellular carcinoma are devastating human malignancies that are characterized by poor prognosis, late onset, and a lack of known biomarkers. New diagnostic and therapeutic molecular targets are desperately needed to develop novel and effective treatment strategies. MicroRNAs (miRNAs) are an emerging class of molecules with roles in various cellular processes, including growth, survival, and apoptosis. Most importantly, aberrant expression of miRNAs has been implicated in cancer pathogenesis. miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma indicate selective overexpression of oncogenic miRNAs and down-regulation of tumor suppressive miRNAs in these cancers. This review summarizes results from key studies conducted to characterize the miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma and describes the potential mechanisms by which some oncogenic or tumor suppressive miRNAs act. Furthermore, this review outlines novel therapeutic strategies for targeting miRNAs.
Li, Wei; LeBrun, Drake G.; Li, Min
[Genetic anomalies of pancreatic carcinoma and clinical applications].
Pancreatic cancer is a dismal disease. The 5-years overall survival ranges from 1% to 5%. Surgery is the only curative treatment available. Survival of selected patients with small lesion (< 2 cm) confined to the pancreas is improved to 19-41%. Presently the major effort is on studies of the cancer development phenomena to improve detection of patients with early lesions. The analysis of oncogene and tumor-suppressor gene activation may enable us to better define and cure this disease. Molecular genetic new tecnquiques performed on pancreatic juice, duodenal juice and stool, probably are the most promising new approach for early diagnosis of pancreatic cancer. This could be the right path to diagnose pancreatic malignant lesions at a curable stage, and to discriminate patients with a more favourable prognosis candidates to be submitted to adjuvant therapy with a curative intent, and also to discriminate real pancreatic cancer from patients with chronic pancreatitis. PMID:11692539
Pantalone, D; Pelo, E; Minuti, B; Mazza, E; Nesi, G; Falchini, M; Ragionieri, I; Pantalone, F; Torricelli, F
Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib
We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.
Ohn, Jung Hun; Kim, Yeong Gi; Lee, Se-Hoon
Spontaneous rupture of a pancreatic acinar cell carcinoma presenting as an acute abdomen
INTRODUCTION Pancreatic acinar cell carcinoma is a rare malignant pancreatic neoplasm. To the best of our knowledge, there has been no report on spontaneous rupture of acinar cell carcinoma. PRESENTATION OF CASE A 39-year-old Azari male presented with a history of sudden onset, acute epigastric pain of 12-h duration. Eight hours later the patient's general condition rapidly deteriorated, blood pressure was decreased to 90/70�mm/Hg and heart rate was increased to 120�beat/min. Emergent abdominal computed tomography scan showed a well-defined hypo-dense, necrotic mass, measured 12�cm�נ12�cm that was originating from the uncinate process of pancreas with marked free peritoneal fluid and extensive haziness of retroperitoneal and mesenteric fat compatible with marked bleeding. Emergent abdominal operation was performed and histopathology revealed acinar cell carcinoma of the pancreas. DISCUSSION Pancreatic acinar cell carcinoma (ACC) usually presents with abdominal pain, nausea and vomiting. To best of our knowledge, no report has been made of spontaneous rupture of ACC. CONCLUSION Pancreatic carcinoma may present as acute abdomen due to rupture of underlying neoplasm.
Mohammadi, Afshin; Porghasem, Jalal; Esmaeili, Arefeh; Ghasemi-rad, Mohammad
Radioimmunolocalization of human pancreatic carcinoma xenograft by 99m Tc-labeled YPC3 monoclonal antibody
Monoclonal antibodies specific to tumor cells may be a useful tool for the diagnosis and treatment of carcinomas. In this study, YPC3 mAb, a specific monoclonal antibody against the human pancreatic carcinoma cell line Capan-2, was labeled directly with99mTc after being pretreated with 2-mercaptoethanol. The radiolabeling efficiency was found to be high (88%�95%) and the immunoreactivity retained, as assessed by
Qikui Chen; Shizhen Yuan
MicroRNA-301b promotes cell invasiveness through targeting TP63 in pancreatic carcinoma cells.
Recent studies have demonstrated that deregulated microRNA (miR) expression is implicated in the development of human cancers. In the aberrant miR expression, miR-301 is upregulated in cancers, such as pancreatic, colorectal and oral carcinoma. Based on this evidence, we investigated the contribution of miR-301 to pancreatic carcinoma and the novel target genes of miR-301 in pancreatic carcinoma. In this study, we analyzed the effects of enforced and inhibited expression of miR-301b expression in the Panc-1 and BxPC-3 cell lines. MiR-301b expression levels were associated with cell invasiveness in both cell lines. Additional experiments indicated that miR-301b influences invasiveness through CDH1. Moreover microRNA target search algorithms and experimental strategies suggested that miR-301b suppressed TP63 expression as a novel target of miR-301b. Remarkably, miR-301b was also found to be associated with NF-?B activity in both cell lines. In summary, overexpressed miR-301b may suppress TP63 expression and contributes to promote cell invasiveness and to enhance gemcitabine resistance in pancreatic carcinoma cells. Thus, miR-301b may have potential as a novel therapeutic target for cancer treatment due to its stimulatory effects on cell invasiveness. PMID:24398967
Funamizu, Naotake; Lacy, Curtis Ray; Parpart, Sonya T; Takai, Atsushi; Hiyoshi, Yukiharu; Yanaga, Katsuhiko
Solitary Pancreatic Metastasis from Renal Cell Carcinoma 6 Years after Nephrectomy
Metastatic cancer to the pancreas is rare and accounts for less than 2% of all pancreatic malignancies. Renal cell cancer, malignant melanoma, lung, colon and breast carcinoma are among the few tumors known to metastasize to the pancreas. The pancreas is a rare site of solitary metastasis, but it is often involved in diffuse metastatic disease. We report a case of a female patient with a solitary mass in the neck of the pancreas following right nephrectomy performed 6 years previously for renal cell carcinoma (RCC). An endoscopic ultrasound (EUS) revealed a well-defined lesion in the neck of the pancreas. Patient underwent EUS-guided fine-needle aspiration and cytopathology confirmed the diagnosis of a metastatic RCC. Solitary pancreatic metachronous metastasis from RCC may rarely occur. The interval between nephrectomy and pancreatic metastasis may be long.
Okasha, Hussein Hassan; Al-Gemeie, Emad Hamza; Mahdy, Reem Ezzat
Immunoelectron study of pancreatic carcinomas using antibodies to gastrointestinal hormones.
The aim of this study was to investigate the ultrastructural appearance of pancreatic adenocarcinoma combined with glucagon and gastrin/cholecystokinin (CCK) expression. The authors investigated the ultrastructure and the immunocytochemistry of 12 human pancreatic cancer specimens and used 3 chronic pancreatitis samples and 6 adjacent histological normal pancreatic tissues (away from the tumor) as controls. The ultrastructural study revealed that chronic pancreatitis tissues were characterized by alterations of the secretory cells. The enzymic and secretory changes were confirmed by electron immunogold results. Glucagon appeared to be located not only in islet alpha cells but also in intermediate alpha acinar cells. The changes were more significant in adenocarcinoma cases. Abnormality in the immunoreaction of the peptides was indicated not only in the tumor area but also in the islets near the cancer. Cells immunoreactive with antibodies were found in all 12 adenocarcinoma cases. Abnormal co-location of both hormones in the same type of endocrine cell was also found. Moderately to poorly differentiated adenocarcinomas were poorly granulated compared with differentiated tumors. Increased and ectopic gastrin/CCK expression was correlated with pancreatic adenocarcinomas exhibiting poor histological grade and neoplastic endocrine cells, providing a potential marker for pancreatic adenocarcinomas with aggressive behavior. PMID:17786831
Seretis, E C; Gavriil, A N; Golematis, V C; Voloudakis-Baltatzis, I E
Antiproliferative effects of interferon alpha on human pancreatic carcinoma cell lines are associated with differential regulation of protein kinase C isoenzymes
BACKGROUND: The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood. AIM: To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines. METHODS: The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. Anchorage
S Rosewicz; M Weder; A Kaiser; E O Riecken
Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography.
OBJECTIVE: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region. SUMMARY BACKGROUND DATA: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy. METHODS: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region). RESULTS: "Occult" metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively). CONCLUSIONS: Staging laparoscopy is indispensable in the detection of "occult" intra-abdominal metastases. Laparoscopic ultrasonography improves the accuracy of laparoscopic staging in patients with potentially resectable pancreatic and periampullary carcinomas. Images Figure 1. Figure 2. Figure 3. Figure 4.
John, T G; Greig, J D; Carter, D C; Garden, O J
[Concomitant gastric and pancreatic metastases from renal cell carcinoma: case study].
This report describes the case of a patient who underwent total gastrectomy, splenectomy and pancreatomy corporo-postero as a consequence of gastric and pancreatic metastasis from carcinoma to clear cells, five years after having undergone radical nephrectomy. Upper digestive bleeding was the first symptom, and pancreatic lesion was detected in previous CT scans. There are many documented cases of pancreatic metastasis, but only eight gastric metastasis in the last 15 years, although we did not find reports about surgical treatment for concomitant gastric and pancreatic injury. Surgical treatment which in some reports include highly complex surgeries such as gastrectomies with combined resections of invaded organs and pancreatoduodenectomy, are good options for select cases, because good survival rates have been reported. PMID:16622491
Portanova, Michel; Yabar, Alejandro; Lombardi, Emilio; Vargas, Fernando; Mena, V�ctor; Carbajal, Ramiro; Palacios, N�stor; Orrego, Jorge
Pancreatic tuberculosis mimicking pancreatic head carcinoma: A case report and review of the literature
Summary A 24-year-old man presented with vague abdominal fullness and a mild epigastric dull pain for about 3 months was found to have a pancreatic head tumor at a medical center 2 months ago. He came to our hospital for further treatment. Ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP) and abdominal computed tomography (CT) all revealede a pancreatic head tumor. Laparotomy was
C. S. Wu; S. H. Wang; T. T. Kuo
[Histological grading of ductal pancreatic carcinomas. Relationship to silver staining of NOR-associated proteins and to p53 immunoreactivity].
The histological grading of 29 ductal pancreatic carcinomas was compared with that of silver stained NOR-associated proteins and with p53 immunoreactivity. The AgNOR number (NZ) and AgNOR areas (NF) of 10 grade I carcinomas, 13 grade II carcinomas and 6 grade III carcinomas were investigated by image analysis. Furthermore, the protein expression of the p53 gene was examined by immunohistochemistry. A significant difference was found in both AgNOR parameters between grade I, grade II and grade III carcinomas (NZ: p < 0.01; NF: p < 0.05; grade I carcinomas: NZ 5.1/NF 8.2 microns 2; grade II carcinomas: NZ 6.0/NF 11.3 microns 2 grade III carcinomas: NZ 8.4/NF 15.2 microns 2). By contrast no relation was found between histological grading and p53 immunoreactivity. In 56% of all carcinomas positive evidence was found of the p53 gene product. (6 grade I carcinomas, 7 grade II carcinomas, 3 grade III carcinomas). 44% of the cases were p53-negative (4 grade I carcinomas, 6 grade II carcinomas, 3 grade III carcinomas). This study demonstrates that the AgNOR technique is useful in the grading of ductal pancreatic carcinomas, whereas the expression of the p53 gene product is not. PMID:7515673
Reich, O; Heinisch, G; Justus, J
Pancreatic metastases from renal cell carcinoma: a case report and literature review of the clinical and radiological characteristics
Metastatic pancreatic cancer is rare, accounting for approximately 2% of all pancreatic malignancies, and most cases arise from renal cell carcinoma. We report the case of a 63-year-old woman, who presented with a pancreatic tumor detected during her annual health examination. She had undergone left nephrectomy 13 years previously for renal cell carcinoma. Computed tomography (CT) revealed two tumors in the head and body of the pancreas, a hypervascular tumor and a hypovascular tumor with an enhanced rim, respectively. She underwent pylorus-preserving pancreaticoduodenectomy, and metastatic pancreatic tumors arising from the kidney with clustered clear cell carcinoma immunohistochemically positive for CD10 were diagnosed. This report presents the different enhancement features of different lesions on CT scans. Because the enhancement features of lesions have been reported to vary according to the size of the metastatic tumor, a knowledge of the history of renal cell carcinoma is crucial for diagnosis.
Percutaneous ethanol ablation of hepatocellular carcinoma: periprocedural onset alcohol toxicity and pancreatitis following conventional percutaneous ethanol ablation treatment.
A novel case of acute pancreatitis in a patient treated with percutaneous ethanol injection (PEI) ablation for hepatocellular carcinoma is described. The most commonly reported adverse effects of PEI are hepatic or peritoneal hemorrhage, hepatic insufficiency or infarction. There are no previous reports of fatal acute pancreatitis as a result of conventional PEI. PMID:19668800
Burton, Kirsteen Rennie; O'Dwyer, Helena; Scudamore, Charles
Percutaneous ethanol ablation of hepatocellular carcinoma: Periprocedural onset alcohol toxicity and pancreatitis following conventional percutaneous ethanol ablation treatment
A novel case of acute pancreatitis in a patient treated with percutaneous ethanol injection (PEI) ablation for hepatocellular carcinoma is described. The most commonly reported adverse effects of PEI are hepatic or peritoneal hemorrhage, hepatic insufficiency or infarction. There are no previous reports of fatal acute pancreatitis as a result of conventional PEI.
Burton, Kirsteen Rennie; O'Dwyer, Helena; Scudamore, Charles
Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma
Little information is currently available concerning the uptake of porphyrins by pancreatic tumors, or the effect of photodynamic therapy (PDT) on pancreatic cancer. In Syrian golden hamsters (n = 33), the organ distribution of /sup 125/I-labeled dihematoporphyrin ether (DHE) was studied in a pancreatic cancer model. In the same animal model the effect of PDT was studied using a gold vapor laser for energy delivery 3 hr after the injection of DHE (n = 7). DHE was 2.4 times more concentrated in the pancreatic tumor than in the nontumorous pancreas at 3 hr. Simultaneously there was a considerable accumulation of DHE in the surrounding gastrointestinal tract, causing perforation of the duodenum and jejunum with resultant death in four (57%) animals after PDT. Photodynamic therapy caused extensive tumor necrosis without any obvious effect on the nontumor-bearing pancreas. Damage to the surrounding tissue in the hamster indicates that precautions should be taken if PDT is to be used clinically in pancreatic cancer. Intratumoral injection of DHE may give higher drug concentrations with greater specificity for tumor treatment.
Schroder, T.; Chen, I.W.; Sperling, M.; Bell, R.H. Jr.; Brackett, K.; Joffe, S.N.
Effectiveness and security of CT-guided percutaneous implantation of (125)I seeds in pancreatic carcinoma.
Objective: To assess the effectiveness and security of CT-guided percutaneous implantation of iodine-125 ((125)I)-labelled seeds in pancreatic carcinoma. Methods: A total of 36 patients (25 males and 11 females) with an average age of 57 years (range, 39-84 years) were enrolled and categorized into Stage III (27 cases) and Stage IV (9 cases) of pancreatic cancer. There were 3 tumours in the pancreatic head and 33 tumours in the pancreatic body or tail. The average diameter of the tumours was 37.1?mm (range, 15-65?mm). The implantation of (125)I seeds was performed by using 18-G needles (length, 150-200?mm) through the anterior, lateral and posterior approaches. Then, (125)I seeds were loaded and released into the lesions. Results: Implantations were performed via the anterior (23 patients), lateral (9 patients) and posterior (4 patients) approaches. During implantation, 3-14 punctures were performed for each patient, and a total of 164 punctures were recorded. Meanwhile, a total of 657 seeds were implanted with an average of 25.27 (range, 12-50) seeds per patient, and the success rate was 100%. The activity of each seed ranged from 0.55 to 0.65?mCi. A main adverse event occurred in one puncture and minor events in seven punctures. No significant relationship between the punctures or adverse events was identified. No serious complication was detected after the implantations during follow-up visits. Conclusion: This study suggested that CT-guided percutaneous implantation of (125)I seeds in a pancreatic carcinoma was relatively safe and effective for treating unresectable pancreatic cancer. Advances in knowledge: The CT-guided percutaneous implantation of (125)I seeds in unresectable pancreatic cancer showed highly successful rates without serious complications. PMID:24734936
Yu, Y-P; Yu, Q; Guo, J-M; Jiang, H-T; Di, X-Y; Zhu, Y
EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation.
Tyrosine kinase receptors have an essential role in various aspects of tumor progression. In particular, epidermal growth factor receptor (EGFR) and its ligands have been implicated in the growth and dissemination of a wide array of human carcinomas. Here, we describe an EGFR-mediated signaling pathway that regulates human pancreatic carcinoma cell invasion and metastasis, yet does not influence the growth of primary tumors. In fact, ligation/activation of EGFR induces Src-dependent phosphorylation of two critical tyrosine residues of p130CAS, leading to the assembly of a Crk-associated substrate (CAS)/Nck1 complex that promotes Ras-associated protein-1 (Rap1) signaling. Importantly, GTP loading of Rap1 is specifically required for pancreatic carcinoma cell migration on vitronectin but not on collagen. Furthermore, Rap1 activation is required for EGFR-mediated metastasis in vivo without impacting primary tumor growth. These findings identify a molecular pathway that promotes the invasive/metastatic properties of human pancreatic carcinomas driven by EGFR. PMID:21963850
Huang, M; Anand, S; Murphy, E A; Desgrosellier, J S; Stupack, D G; Shattil, S J; Schlaepfer, D D; Cheresh, D A
Pancreatic mass lesion mimicking carcinoma: initial presentation of retroperitoneal fibrosis.
A 63-year-old woman with upper abdominal pain radiating to her back was admitted to the hospital, and a mass lesion was identified involving pancreatic body and tail, with peripancreatic lymph node enlargement. The patient had normal tumor marker levels, a very high erythrocyte sedimentation rate (104) and negative malignant cells in fine needle aspiration cytology. The patient underwent laparotomy and histological findings of mass were consistent with retroperitoneal fibrosis. She has been in remission after long-term steroid treatment. In the differential diagnosis of cases with pancreatic mass lesion, retroperitoneal fibrosis should also be considered. PMID:16245228
Kaya, Muhsin; Aydin, Fatih
Advanced pancreatic carcinoma: current treatment and future challenges
Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth leading cause of cancer-related death in North America. Most patients present with locally advanced or metastatic disease that precludes curative resection. These patients have an extremely poor prognosis. In the absence of effective screening methods, considerable efforts have been made during the past decade to identify better
Anastasios Stathis; Malcolm J. Moore
Postmortem examination of 22 pancreatic carcinoma patients treated with helium ion irradiation
Postmortem findings are available in this report in 22 patients with pancreatic carcinoma treated with helium ions at Lawrence Berkeley Laboratory; California. This represents the largest group evaluated histologically in the literature and is the first report evaluating effects of particle radiation in pancreatic tissue. Patient survival after therapy averaged 9 months. Most died of infection and/or pulmonary emboli. Local control was achieved in 27%. The pancreatic tumors had histologically more severe radiation changes than nontumor bearing pancreas. Irradiated bone marrow was severely hypocellular, and irradiated skin was atrophic. Five patients had radiation injury in the gastrointestinal tract. The spinal cord, liver, and kidneys showed no damage. This study demonstrates the safety of helium particle irradiation with present therapeutic planning. Injury to tumor was seen without excessive damage to adjacent tissues.
Woodruff, K.H.; Castro, J.R.; Quivey, J.M.; Saunders, W.M.; Chen, G.T.; Lyman, J.T.; Pitluck, S.; Tobias, C.A.; Walton, R.E.; Peters, T.C.
Incidence and pathology of pancreatic carcinoma among atomic bomb survivors, 1950-1982
There is little evidence that pancreatic carcinoma is radiogenic in humans. To further investigate this possibility, all follow-up sources at the Radiation Effects Research Foundation were utilized to identify 378 incident cases of pancreatic cancer which occurred between October 1, 1950 and December 31, 1982 among 91,231 members of the cohort of atomic bomb survivors in Hiroshima and Nagasaki, Japan. An independent pathology review was conducted for all eligible cases, and pathology reports and slides were sought for those having a tissue diagnosis. The incidence of pancreatic carcinoma in this cohort was evaluated with respect to city, sex, age at exposure, time since exposure, radiation dose, and selected pathologic characteristics. Radiation dose effects, as well as spontaneous (background) incidence rates, were estimated using generalized Poisson regression models. Allowing for natural variations in background incidence, a significantly increased risk of pancreatic cancer was found to be associated with atomic bomb radiation exposure (relative risks = 1.3,95% confidence interval = 1.1-1.6). This relationship was much stronger in Nagasaki than Hiroshima, and among males than females. Age at exposure and time since exposure had little effect on radiation risk estimates. The interpretation of these findings in relation to their biologic plausibility is stressed, and the implications of using Radiation Effects Research Foundation incidence data in this regard are discussed.
Davis, S.; Yamamoto, T.
Contrast-enhanced sonography of pancreatic carcinoma: correlations with pathological findings
Background. We examined contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma in relation to the pathological findings in resected specimens to evaluate correlations between observations made by this modality and the pathological findings. Methods. The pathological findings of surgical specimens obtained from 16 patients were examined in relation to the contrast-enhanced harmonic gray-scale sonography findings. Lesion vascularity was examined by
Kazushi Numata; Yutaka Ozawa; Noritoshi Kobayashi; Toru Kubota; Hiroshi Shimada; Akinori Nozawa; Yukio Nakatani; Kazuya Sugimori; Kenichi Matsuo; Toshio Imada; Katsuaki Tanaka
Surgical selection for late pancreatic head carcinoma without gastric outlet obstruction.
The effects of different surgical procedures for late pancreatic head carcinoma without gastric outlet obstruction were explored in order to provide theoretical basis to select a suitable operation for these patients. The clinical data of 441 cases of late pancreatic head carcinoma without gastric outlet obstruction were retrospectively analyzed. All patients were divided into 4 groups based on different surgical procedures: group A (101 cases) subjected to Roux-en-Y cholecystojejunostomy; group B (133 cases) undergoing Roux-en-Y choledochojejunostomy; group C (83 cases) given Roux-en-Y cholecystojejunostomy combined with gastrojejunostomy; group D (124 cases) receiving Roux-en-Y choledochojejunostomy combined with gastrojejunostomy. Therapeutic efficacy in each group was evaluated comparatively. Both groups B and D had a lower rate of postoperative obstructive jaundice than groups A and C separately (P<0.05 for all). The data of mean life span showed that both groups B and D had a lower survival rate than groups A and C separately (P<0.05 for all). The incidence of postoperative gastric outlet obstruction in groups A and B was higher than that in groups C and D separately (P<0.05 for all). The gastrojejunostomy had no impacts on the mean life span, and there was no statistically significant difference in complications, average hospital stay (days) and median survival among four groups (P>0.05). For the late pancreatic head carcinoma without gastric outlet obstruction, Roux-en-Y choledochojejunostomy is effective for the reduction of icteric index and the incidence of recurrent jaundice, also offers an opportunity for prolonged survival. Combined use of prophylactic Roux-en-Y gastrojejunostomy during surgical biliary drainage is safe for advanced pancreatic carcinoma with obstructive jaundice, which can decrease the incidence of postoperative gastric outlet obstruction, and has important implications for improving outcomes. PMID:24337850
Zhang, Shu-hua; Wang, Juan; Yang, Chong; Wang, Bo; Wu, He-shui; Wang, Chun-you
Photodynamic therapy for pancreatic and biliary tract carcinoma
The prognosis of patients with pancreatic and biliary tract cancer treated with conventional therapies such as stent insertion\\u000a or chemotherapy is often poor, and new approaches are urgently needed. Surgery is the only curative treatment but is appropriate\\u000a in less than 20% of cases, and even then it is associated with a 5-yr survival of less than 30% in selected
Lakshmana Ayaru; Stephen G. Bown; Stephen P. Pereira
A novel antiangiogenic approach for adjuvant therapy of pancreatic carcinoma
Introduction��Surgical therapy remains the only curative option for pancreatic ductal adenocarcinoma. But even after complete resection,\\u000a almost all patients suffer from local tumor recurrence. Current standard adjuvant therapy with gemcitabine does not impressively\\u000a affect the recurrence rate. The aim of this study was to evaluate a novel anti-angiogenic adjuvant treatment strategy by targeting\\u000a the vascular endothelial growth factor receptor (VEGFR).
Peer Joensson; Birgit Hotz; Heinz Johannes Buhr; Hubert G. Hotz
Comparison of pancreatic acinar cell carcinoma and adenocarcinoma using multidetector-row computed tomography
AIM: To distinguish acinar cell carcinoma (ACC) from pancreatic adenocarcinoma (AC) by comparing their computed tomography findings. METHODS: Patients with ACC and AC were identified on the basis of results obtained using surgically resected pancreatectomy specimens. The preoperative computer tomographic images of 6 acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4 phases (non-contrast, arterial, portal venous, and delayed phase) were compared. The scan delay times were 40, 70, and 120 s for each contrast-enhanced phase. The visual pattern, tomographic attenuation value, and time attenuation curve were assessed and compared between AC and ACC cases using the ?2 test, Wilcoxon signed-rank test, and Mann Whitney U test. RESULTS: The adenocarcinomas tended to be hypodense in all 4 phases. The acinar cell carcinomas also tended to be hypodense in the 3 contrast-enhanced phases, although their computed tomographic attenuation values were higher. Further, 5 of the 6 acinar cell carcinomas (83%) were isodense in the non-contrast phase. The time attenuation curve of the adenocarcinomas showed a gradual increase through the 4 phases, and all adenocarcinomas showed peak enhancement during the delayed phase. The time attenuation curve of the acinar cell carcinomas showed peak enhancement during the portal venous phase in 4 cases and during the arterial phase in 2 cases. None of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase. CONCLUSION: The tumor density in the non-contrast phase and time attenuation curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas, and multidetector-row computed tomography can thus distinguish these tumors.
Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Kozuki, Akihito; Nakamura, Toshio
Pancreatic Fibrosis Correlates with Exocrine Pancreatic Insufficiency after Pancreatoduodenectomy
Background: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic
T. C. K. Tran; G. van �t Hof; G. Kazemier; W. C. J. Hop; C. J. Pek; A. W. van Toorenenbergen; H. van Dekken; C. H. J. van Eijck
Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells1
Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU) alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5) influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days) did not alter the messenger RNA (mRNA) expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1), whereas high dosages of the drug (20 �M for 1 hour) elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine), the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1) or MRP5-silenced (PANC1/shMRP5) cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.
Hagmann, Wolfgang; Jesnowski, Ralf; Lohr, Johannes Matthias
Indirect antiproliferative effect of the somatostatin analog octreotide on MIA PaCa-2 human pancreatic carcinoma in nude mice.
Analogs of somatostatin (SRIF) such as octreotide exert antiproliferative effects that are mediated directly by tumoral SRIF receptors or indirectly by down-modulation of factors that stimulate tumor growth. Direct and indirect antiproliferative effects have been demonstrated in certain SRIF receptor-positive and -negative human breast cancer models in nude mice, respectively. These antiproliferative mechanisms are also being explored in other cancer types including pancreatic cancer. While clinical pilot studies have indicated that a fraction of pancreatic adenocarcinomas respond to high-dose octreotide treatment, it is known from receptor autoradiographic and scintigraphic studies that human pancreatic carcinomas fail to express SRIF receptors, in contrast to rat pancreatic carcinomas or human endocrine pancreatic cancer. Studies on the potential anticancer effect of octreotide on the growth of experimental human pancreatic cancer and its SRIF receptor status have been controversial. Therefore, we investigated in vivo the effects of octreotide on the growth of MIA PaCa-2 human pancreatic carcinomas raised from cultured cells with a low passage number after receipt from the American Type Culture Collection. Nude mice bearing MIA PaCa-2 tumors were treated with a single injection of the recently developed octreotide long-acting release formulation, "SMS pa LAR." This treatment was well tolerated and resulted in a highly significant inhibition of tumor growth during weeks three and eight after administration. MIA PaCa-2 tumors were removed after eight weeks and processed for RT-PCR analysis using probes specific for each of the five somatostatin receptor subtypes sst1-sst5. This analysis revealed that MIA PaCa-2 tumors, like human pancreatic adenocarcinomas, do not express any of the five SRIF receptor subtypes, suggesting an indirect mode of tumor growth inhibition. In summary, the depot formulation SMS pa LAR exerted long-lasting antiproliferative effects in SRIF receptor-negative human pancreatic carcinomas in nude mice. Images Figure 3
Weckbecker, G.; Raulf, F.; Bodmer, D.; Bruns, C.
... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...
Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families.
Families with both melanoma and pancreatic cancer are extremely rare and some are affected with the autosomal dominant inherited familial atypical multiple mole melanoma-pancreatic cancer (FAMMM-PC) syndrome. The phenotypic and genotypic expressions of such pancreatic cancer-melanoma prone families are not well defined. The National Case Collection of Familial Pancreatic Cancer of the Deutsche Krebshilfe includes 110 pancreatic cancer families, 18 of which (16%) show an association of pancreatic cancer and melanoma. These 18 families were analysed regarding their phenotype and the prevalence of germline mutations in the candidate genes CDKN2A, BRCA2, CHEK2, NOD2, ARL11 and Palladin (PALLD). There were two types of families: five families with the FAMMM-PC phenotype and 13 PC/melanoma families without the multiple mole phenotypes (PCMS). The prevalences of PC and melanoma in the two types of families were similar. The prevalence of other tumour types, especially breast carcinoma, was higher (11%) in PCMS- than in FAMMM-PC families (2.4%, p = 0.02). CDKN2A mutations were identified in 2 of 18 (11%) PCMS families. A cosegregating BRCA2 mutation was detected in one PCMS family without breast cancer. None of the reported germline mutations in the NOD2, Palladin, ARL11 or CHEK2 genes were detected in either type of family. In conclusion, families with an accumulation of PC and melanoma show a large variety of phenotypic expression, which is not always consistent with the FAMMM-PC phenotype. More PC/melanoma-prone families need to be analysed to clarify whether such families represent variations of the FAMMM-PC syndrome or two distinct hereditary cancer syndromes. PMID:20041885
Bartsch, D K; Langer, P; Habbe, N; Matth�i, E; Chaloupka, B; Sina, M; Hahn, S A; Slater, E P
Palmar fasciitis and polyarthritis syndrome in pancreatic carcinoma.
Palmar fasciitis and polyarthritis syndrome is a rare paraneoplastic condition that may portend a diagnosis of malignancy. We describe the case of a 73-year-old man who presented with progressive palmar swelling, erythema, pain, and contractures of both hands, This presentation and associated weight loss eventually led to the diagnosis of metastatic pancreatic adenocarcinoma. This case highlights the often delayed, but important diagnosis of this unusual paraneoplastic phenomenon which can mimic arthropathy, Dupuytren contracture, and scleroderma. Our case is also the first documentation of the extensive inflammatory magnetic resonance imaging changes in palmar fasciitis and polyarthritis syndrome, which affects all tissue planes including the synovium and explains its confusing clinical manifestations. PMID:23669802
Veitch, David; Tsai, Ted; Joshua, Fredrick
Fluorine18 fluorodeoxyglucose positron emission tomography in the differential diagnosis of pancreatic carcinoma: a report of 106 cases
The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as a tool for the differential diagnosis of pancreatic carcinoma while taking into account serum glucose level. A group of 106 patients with unclear pancreatic masses were recruited for the study. PET was performed following intravenous administration of an average of 190 MBq [18F]FDG. Focally
Michael Zimny; Roland Bares; J�rgen Fa�; Gerhard Adam; Uwe Cremerius; Bernhard Dohmen; Peter Klever; Osama Sabri; Volker Schumpelick; Udalrich Buell
Endosonography and cytology in diagnosing and staging pancreatic body and tail carcinoma: Preliminary results of endosonographic guided puncture
Endosonography was performed in diagnosing and staging pancreatic body and tail carcinoma in two patients. In the first case endoscopy, abdominal ultrasound, and computed tomography were nondiagnostic in diagnosing the origin of submucosal gastric abnormalities. Endosonography diagnosed a pancreatic tail carcinoma with submucosal gastric involvement, and this was confirmed by endosonographic-guided cytology. Fundus varices due to segmented splenic vein involvement were found. Surgery was not recommended due to the advanced disease. In the second case pancreatic body carcinoma was diagnosed by ERCP and computed tomography. Transcutaneous ultrasonographic-guided cytological puncture confirmed the diagnosis. Endosonography revealed additional information of segmental portal hypertension with fundic varices due to splenic vein involvement. Autopsy confirmed the endosonographic diagnosis. 18 refs., 5 figs.
Tio, T.L.; Sie, L.H.; Tytgat, G.N.J. (Georgetown Univ. Medical Center, Washington, DC (United States) Academic Medical Center, Amsterdam (Netherlands))
[Prognostic value of molecular biologogy and immunologic parameters in human pancreatic carcinoma].
In the present study we investigated the prognostic relevance of molecular and immunological changes in pancreatic carcinoma. 82 tissue specimens of adenocarcinoma of the pancreas were stained immunohistochemically with following factors: p53, p21WAF1, Cyklin D, EGF, EGF-R, cERB-B2, CD95, BCL-2 and Cathepsin D. We further determined the serum levels of sCD44, sCD44v6, neopterin and IL-2R. Except Cyclin D none of the immunohistochemically determined factors had prognostic significance. Interestingly all of the immunological serum parameters were of high prognostic significance. These data demonstrate the prognostic relevance of immunological parameters in human adenocarcinoma of the pancreas and could raise the possibility of an early immunological intervention in pancreatic cancer. PMID:14518215
Gansauge, F; Gansauge, S; M�ller, J; Schmid, E; Beger, H G
Solitary pancreatic lymph node metastasis from carcinoma of the breast: case report
Background We report the first case of isolated pancreatic lymph node recurrence in a locally advanced breast cancer patient. Case A 41-year old woman underwent radical mastectomy according to Madden and removal of axillary lymph nodes for multicentric infiltrating ductal carcinoma pathologically staged as pT2N2M0. After six years from primary diagnosis, and four years from the diagnosis of lung recurrence, she developed an isolated metastatic lesion to pancreatic lymph node. After surgical excision of metastasis, hormone therapy with Exemestane was begun. At 16 months of follow-up, the patient appears free of disease. Conclusion Because metastatization to visceral organ carries a very unfavorable prognosis, we think that the clinical significance of the elevation of CA 15.3 serum levels in the early detection of recurrence and in monitoring metastatic disease during follow-up, should be not underestimated.
Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome
CD4+CD25+FoxP3+ regulatory T cells (Tregs) are understood to maintain peripheral tolerance to self-antigens and inhibit antitumor immune responses. However, compelling evidence suggests that, Tregs provide no anti-inflammatory protection in the tumor microenvironment, but rather contribute to a T helper 17 (Th17)-driven pro-carcinogenic process. Using three-color flow cytometry, we evaluated the percentage of circulating CD4+CD25+FoxP3+ Tregs in the peripheral blood of pancreatic carcinoma patients prior to and after chemotherapy [gemcitabine (GEM) alone, or GEM+oxaliplatin (GEMOX) or bevacizumab+capecitabine+radiotherapy (BEV+CAPE+RT)]. Correlations were sought between Treg counts and plasma levels of cytokines relevant to controlling the Treg/Th17 balance, i.e., interleukin (IL)-23, IL-17A, IL-6 and transforming growth factor ? 1 (TGF-?1), as measured by ELISA and the clinical features of pancreatic cancer. Treg, IL-6 and TGF-?1 levels were higher in locally advanced and metastatic pancreatic carcinoma patients compared to controls. No parameter was correlated with disease stage except IL-6. IL-17A and TGF-?1 were significantly associated with increased risk of poor prognosis. IL-17A was positively correlated with IL-23. Treg and IL-6 levels decreased following GEM monochemotherapy, IL-17A levels decreased after GEMOX, and IL-6 levels were reduced subsequent to BEV+CAPE+RT treatment. IL-23, IL-17A and TGF-?1 levels were significantly lower in patients responding to chemotherapy (partial remission/stable disease) than in nonresponders to chemotherapy (progressive disease). These results suggest an impact of the Treg/Th17-balance in pancreatic carcinoma, highlighting the significance of TGF-?1 and IL-17A as potential prognostic and predictive indicators. Immunological changes induced by mono and/or combined chemotherapy indicate specific windows of opportunity for introducing integrative interventions on a new target in pancreatic cancer, i.e. IL-17A, possibly improving survival in this highly lethal disease.
Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts
Background Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-EGF receptor and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. Materials and Methods Nude mice, bearing human pancreatic carcinoma, xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab), or gemcitabine and tumor growth were observed. Results and Conclusion In first-line therapy, mice survival was significantly longer in 2mAbs groups compared to gemcitabine (p<0.0001: BxPC-3; p=0.0679: MiaPaCa-2; p=0.0019: Capan-1) and to controls (p<0.0001). In second-line therapy tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival, compared with mice receiving continuous gemcitabine injections (p=0.008, BxPC-3; p=0.05; MiaPaCa-2; p<0.001, Capan-1). Therapeutic benefit of 2mAbs was observed, despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab)?2 fragments from 2mAbs induced significant tumor growth inhibition, compared to controls (p=0.001), indicating that the 2mAbs had an, Fc-independent, direct action on tumor cells. This pre-clinical study demonstrated a significant improvement of survival and tumour regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first and second-line treatments, compared to gemcitabine, independently of the K-Ras status.
Larbouret, Christelle; Robert, Bruno; Bascoul-Mollevi, Caroline; Penault-Llorca, Frederique; Ho-Pun-Cheung, Alexandre; Morisseau, Sebastien; Navarro-Teulon, Isabelle; Mach, Jean-Pierre; Pelegrin, Andre; Azria, David
Prognostic significance of molecular alterations in human pancreatic carcinoma � an immunohistological study
Background: During the last decade, many molecular alterations have been described for pancreatic carcinomas. However, the clinical and\\u000a prognostic value of these alterations has been discussed and is controversial. Methods: An immunhistochemical study was performed in 82 cases of adenocarcinoma of the pancreas. Using specific antibodies, expression\\u000a of EGF, EGF-receptor, cERB-B2, p53, p21CIP1, cyclin-D1, BCL-2, CD95 and KI67 was evaluated.
Frank Gansauge; Susanne Gansauge; Erika Schmidt; J�rg M�ller; Hans G. Beger
Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival
Cytokine shedding by tumor cells into the local microenvironment modulates host immune response, tumor growth, and metastasis.\\u000a The study aimed to verify the hypothesis that the immunological microenvironment of pancreatic carcinoma exists in a prevalently\\u000a immunosuppressive state, influencing survival. We analyzed expression profiles of pro-inflammatory (IL-1?, IL-2, IL-6, IL-8,\\u000a IL-12 p40, IL-18 and IFN-?) and anti-inflammatory (IL-10, IL-11, IL-13 and
Graziella Bellone; Carlo Smirne; Francesco Angelo Mauri; Elena Tonel; Anna Carbone; Alessandra Buffolino; Luca Dughera; Antonio Robecchi; Mario Pirisi; Giorgio Emanuelli
CD44 in normal human pancreas and pancreatic carcinoma cell lines.
CD44 is an integral cell-surface glycoprotein. Overexpression of the CD44 standard (CD44st) and its variants (CD44v) has been implicated in transformation and progression of many cancer types. Here, we investigated expression of CD44st, CD44v3-7, CD44v7/8, and v10 in five human pancreatic tumor cell lines and normal human pancreatic duct cells transfected with the SV40 large T antigen. CD44st and its variant proteins were quantified using immunocytochemistry and flow cytometry. CD44v7 was expressed at low levels, whereas CD44st, CD44v3, CD44 v4, CD44v, and CD44v6 were expressed at moderate levels in all pancreatic tumor cell lines. In contrast, CD44v7/8 and CD44v10 were expressed at very low levels in two out of the five pancreatic tumor cell lines. Overall, staining of CD44st and CD44 variants was significantly weaker compared to another surface molecule, ICAM-1, reported to be overexpressed in pancreatic cancer cells. Furthermore, the SV40 large T transfected duct cells showed only a weak staining for CD44st, CD44v5, and CD44v6. To determine a possible mechanism for the regulation of surface expression of CD44st, v5 and v6, we incubated Panc-1 cells with bFGF, TGF-beta1, EGF, TNFalpha, and IFNgamma. Only IFNgamma affected the CD44 expression by down-regulation of CD44v6. The constitutive expression of CD44 variants seems to be associated with the malignant state of invasive carcinoma. PMID:11135324
Ringel, J; Jesnowski, R; Schmidt, C; Ringel, J; K�hler, H J; Rychly, J; Batra, S K; L�hr, M
APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM.
Despite intensive multimodal therapies, the overall survival rate of patients with ductal adenocarcinoma of the pancreas is still poor. The chemo- and radioresistance mechanisms of this tumor entity remain to be determined in order to develop novel treatment strategies. In cancer, endocytosis and membrane trafficking proteins are known to be utilized and they also critically regulate essential cell functions like survival and proliferation. On the basis of these data, we evaluated the role of the endosomal proteins adaptor proteins containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif (APPL)1 and 2 for the radioresistance of pancreatic carcinoma cells. Here, we show that APPL2 expression in pancreatic cancer cells is upregulated after irradiation and that depletion of APPL proteins by small interfering RNA (siRNA) significantly reduced radiation survival in parallel to impairing DNA double strand break (DSB) repair. In addition, APPL knockdown diminished radiogenic hyperphosphorylation of ataxia telangiectasia mutated (ATM). Activated ATM and APPL1 were also shown to interact after irradiation, suggesting that APPL has a more direct role in the phosphorylation of ATM. Double targeting of APPL proteins and ATM caused similar radiosensitization and concomitant DSB repair perturbation to that observed after depletion of single proteins, indicating that ATM is the central modulator of APPL-mediated effects on radiosensitivity and DNA repair. These data strongly suggest that endosomal APPL proteins contribute to the DNA damage response. Whether targeting of APPL proteins is beneficial for the survival of patients with pancreatic adenocarcinoma remains to be elucidated. PMID:24763056
Hennig, J; McShane, M P; Cordes, N; Eke, I
APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM
Despite intensive multimodal therapies, the overall survival rate of patients with ductal adenocarcinoma of the pancreas is still poor. The chemo- and radioresistance mechanisms of this tumor entity remain to be determined in order to develop novel treatment strategies. In cancer, endocytosis and membrane trafficking proteins are known to be utilized and they also critically regulate essential cell functions like survival and proliferation. On the basis of these data, we evaluated the role of the endosomal proteins adaptor proteins containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif (APPL)1 and 2 for the radioresistance of pancreatic carcinoma cells. Here, we show that APPL2 expression in pancreatic cancer cells is upregulated after irradiation and that depletion of APPL proteins by small interfering RNA (siRNA) significantly reduced radiation survival in parallel to impairing DNA double strand break (DSB) repair. In addition, APPL knockdown diminished radiogenic hyperphosphorylation of ataxia telangiectasia mutated (ATM). Activated ATM and APPL1 were also shown to interact after irradiation, suggesting that APPL has a more direct role in the phosphorylation of ATM. Double targeting of APPL proteins and ATM caused similar radiosensitization and concomitant DSB repair perturbation to that observed after depletion of single proteins, indicating that ATM is the central modulator of APPL-mediated effects on radiosensitivity and DNA repair. These data strongly suggest that endosomal APPL proteins contribute to the DNA damage response. Whether targeting of APPL proteins is beneficial for the survival of patients with pancreatic adenocarcinoma remains to be elucidated.
Hennig, J; McShane, M P; Cordes, N; Eke, I
Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells
The mammalian target of rapamycin (mTOR) is a protein kinase that regulates protein translation, cell growth, and apoptosis. Rapamycin (RPM), a specific inhibitor of mTOR, exhibits potent and broad in vitro and in vivo antitumor activity against leukemia, breast cancer, and melanoma. Recent studies showing that RPM sensitizes cancers to chemotherapy and radiation therapy have attracted considerable attention. This study aimed to examine the radiosensitizing effect of RPM in vitro, as well as its mechanism of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay showed that 10 nmol/L to 15 nmol/L of RPM had a radiosensitizing effects on pancreatic carcinoma cells in vitro. Furthermore, a low dose of RPM induced autophagy and reduced the number of S-phase cells. When radiation treatment was combined with RPM, the PC-2 cell cycle arrested in the G2/M phase of the cell cycle. Complementary DNA (cDNA) microarray and reverse transcription polymerase chain reaction (RT-PCR) revealed that the expression of DDB1, RAD51, and XRCC5 were downregulated, whereas the expression of PCNA and ABCC4 were upregulated in PC-2 cells. The results demonstrated that RPM effectively enhanced the radiosensitivity of pancreatic carcinoma cells.
Dai, Zhi-Jun; Gao, Jie; Kang, Hua-Feng; Ma, Yu-Guang; Ma, Xiao-Bin; Lu, Wang-Feng; Lin, Shuai; Ma, Hong-Bing; Wang, Xi-Jing; Wu, Wen-Ying
Nanoelectroablation of Human Pancreatic Carcinoma in a Murine Xenograft Model without Recurrence
We have identified an effective nanoelectroablation therapy for treating pancreatic carcinoma in a murine xenograft model. This therapy initiates apoptosis in a nonthermal manner by applying low energy electric pulses 100 ns long and 30 kV/cm in amplitude to the tumor. We first identified the minimum pulse number required for complete ablation by treating 30 tumors. We found that the minimum number of pulses required to ablate the tumor with a single treatment is between 250 and 500 pulses. We settled on a single application of either 500 or 1000 pulses to treat pancreatic carcinomas in 19 NIH-III mice. Seventeen of the 19 treated tumors exhibited complete regression without recurrence. Three mice died of unknown causes within 3 months after treatment but 16 lived for 270�302 days at which time we sacrificed them for histological analysis. In the 17 untreated controls, the tumor grew so large that we had to sacrifice all of them within 4 months.
Nuccitelli, Richard; Huynh, Joanne; Lui, Kaying; Wood, Ryan; Kreis, Mark; Athos, Brian; Nuccitelli, Pamela
Antagonistic interactions between gemcitabine and 5-fluorouracil in the human pancreatic carcinoma cell line Capan-2.
Although the recently-developed Gemcitabine (GEM) has renewed interest in clinical research in pancreatic carcinoma, it offers modest improvement of tumor-related symptoms and marginal survival advantage, even when combined with other currently-available chemotherapeutic agents such as 5-Fluorouracil (5-FU). We hypothesized that this disappointing result could be due to an interaction between the two drugs affecting cytotoxic activity. We measured in-vitro growth inhibition, cell cycle distribution, gene and protein expression of apoptosis regulators bcl-2, bcl-x and survivin, NFkappaB and telomerase activities of human pancreatic carcinoma cell line Capan-2 following exposure to GEM and 5-FU singly or combined, by MTT assay and median effect analysis, flow cytometry, real-time RT-PCR, Western blotting, electrophoretic mobility shift assay (EMSA) and telomeric repeat amplification protocol (TRAP) assay, respectively. We found cell growth to be inhibited by both drugs, decreasing the percentage of cells in S and G2/M phases and inducing apoptosis, dependent on the levels of bcl-2, bcl-xL and survivin expression in the case of 5-FU, but not for GEM. Moreover, while telomerase activity was reduced equally by both drugs, 5-FU but not GEM effectively downregulated NFkappaB binding activity. Intriguingly, a substantial antagonistic effect was noticed when GEM was combined with 5-FU in the concentration range tested, with the exception of the TRAP assay. These indications of an antagonistic interaction between GEM and 5-FU in some pancreatic cancer context urge further investigation of both genetic and non-genetic differences to identify the variables most relevant for optimal selection and dosing of treatment for the individual patient. PMID:16929163
Bellone, Graziella; Carbone, Anna; Busso, Valeria; Scirelli, Tiziana; Buffolino, Alessandra; Smirne, Carlo; Novarino, Anna; Bertetto, Oscar; Tosetti, Luciano; Emanuelli, Giorgio
Thickening of the celiac axis and/or superior mesenteric artery: a sign of pancreatic carcinoma on computed tomography
Of 53 patients with carcinoma of the pancreas studied by computed tomography, 20 (37.7%) had apparent thickening of either the celiac axis or superior mesenteric artery. In 6 of them, the pancreatic mass was poorly defined. The frequency of this sign, correlation with angiographic findings, and pathogenesis are discussed.
Megibow, A.J.; Bosniak, M.A.; Ambos, M.A.; Beranbaum, E.R.
CD44v/CD44s expression patterns are associated with the survival of pancreatic carcinoma patients
Background and purpose CD44 variants have been associated with tumor invasion and metastasis, but CD44 expression patterns have not been systematically investigated in pancreatic carcinoma. This study systematically investigated whether CD44 expression patterns are involved in pancreatic carcinoma metastasis and prognosis. Methods We applied primers specific for all CD44 variants and CD44s to analyze the expression patterns of CD44 (CD44v2-CD44v10 and CD44s) using quantitative real-time PCR (qRT-PCR). We then further evaluated their roles in pancreatic carcinoma metastasis and prognosis using clinical survival analysis. Results Increased CD44v expression and decreased CD44s expression were found in metastatic pancreatic carcinoma in three different cell lines and in human tumor tissue. Clinical analysis showed that CD44v6+ and CD44v9+ were correlated with lymph node metastasis, liver metastasis and TNM stage. However, CD44s? was associated with liver metastasis, tumor differentiation and TNM stage. Survival analysis showed that patients with CD44v6+/CD44s? or CD44v6+/CD44s? had lower overall survival (OS) rates, although the individual expression of CD44v6, CD44v9 and CD44s was also related to decreased OS rates. Univariate analysis showed that lymph node metastasis; vessel invasion; hepatic metastases; TNM stage; and individual or co-expression of CD44v6, CD44v9 and CD44s were risk factors affecting survival. Multivariate analysis showed that CD44v6+/CD44s? was an independent predictor of survival. Conclusions We found that CD44v6+, CD44v9+ and CD44s? were associated with pancreatic carcinoma metastasis and progression and that CD44v6+/CD44s? was an independent risk factor affecting survival in pancreatic carcinoma. Therefore, the different expression patterns of CD44v/CD44s may determine pancreatic carcinoma prognosis. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1579257224116287.
Repeated Pancreatectomy for Metachronous Duodenal and Pancreatic Metastases of Renal Cell Carcinoma
A 50-year-old woman had undergone left nephrectomy for renal cell carcinoma 13 years previously. Ten years later, a solitary metastatic tumor had been detected in the pancreatic tail and she had undergone subsequent resection of the pancreatic tail and spleen. Three years after surgery, she was admitted to our hospital for severe anemia resulting from gastrointestinal tract bleeding. Esophagogastroduodenoscopy revealed a 3-cm solid tumor at the oral side of the papilla of Vater. Histology of the bioptic duodenal tissue revealed inflammatory granulation without malignancy. Computed tomography showed a well-contrasted hypervascular tumor in the descending portion of the duodenum. We diagnosed the patient with metachronous duodenal metastasis of renal cell carcinoma and performed a pancreaticoduodenectomy. An ulcerated polypoid mass was detected at the oral side of the papilla of Vater. Histology revealed clear cell carcinoma coated by granulation tissue across the surface of the tumor. Immunohistology demonstrated that the cells were positive for vimentin, CD10 and epithelial membrane antigen and negative for CK7. After a repeated pancreatectomy, the patient had no symptoms of gastrointestinal bleeding and maintained good glucose tolerance without insulin therapy because the remnant pancreas functioned well. In conclusion, for the diagnosis of patients who have previously undergone nephrectomy and present with gastrointestinal bleeding, the possibility of metastasis to the gastrointestinal tract, including the duodenum, should be considered. With respect to surgical treatment, the pancreas should be minimally resected to maintain a free surgical margin during the first surgery taking into account further metachronous metastasis to the duodenum and pancreas.
Hata, Tatsuo; Sakata, Naoaki; Aoki, Takeshi; Yoshida, Hiroshi; Kanno, Atsushi; Fujishima, Fumiyoshi; Motoi, Fuyuhiko; Masamune, Atsushi; Shimosegawa, Tooru; Unno, Michiaki
[A comparison of the diagnostic accuracy of ultrasound, computer tomography and ERPC in chronic pancreatitis and carcinoma of the pancreas (author's transl)].
A comparison of the diagnostic accuracy of ultrasound, computer tomography and ERPC in chronic or recurrent pancreatitis and pancreatic carcinoma has shown that ERPC is the most precise of the three methods. This was particularly important in the demonstration of the small, still operable, carcinomas of the pancreas. Sonography is most useful for serial observations of pancreatic pseudocysts due to chronic recurrent pancreatitis. In this situation, ERPC should only be used if sonography and computer tomography cannot localise the lesion. Where the computer tomogram has shown evidence of enlargement of the pancreas, sonography may show an area devoid of echos within the enlarged organ, suggesting the presence of a carcinoma. Computer tomography superior to ultrasonography in delineating the extent of extensive pancreatic disease and in showing the anatomical structures surrounding the pancreas. PMID:6452353
Gmelin, E; Weiss, H D; Fuchs, H D; Reiser, M
Expansion of Anti-Mesothelin Specific CD4+ and CD8+ T Cell Responses in Patients with Pancreatic Carcinoma
We aimed to assess the status of naturally occurring CD4+ and CD8+ T cell responses to a tumour associated antigen, Mesothelin, in patients with pancreatic carcinoma and study the effects of elevated IL-10 on Mesothelin-specific T cell responses. For that sake, short term T cell lines were generated from PBMCs of 16 healthy controls, 15 patients with benign pancreatic diseases and 25 patients with pancreatic carcinoma and Mesothelin-specific CD4+ and CD8+ T cell responses were analysed using intracellular cytokine assays for IFN-?. Plasma levels of IL-10 and Mesothelin were measured using cytometric bead array and ELISA assay, respectively. The blocking assays were performed to assess the effects of IL-10 on Mesothelin-specific T cell responses. Here, we demonstrate that the plasma levels of Mesothelin and IL-10 are significantly increased in patients with pancreatic carcinoma. Additionally, we found that (a) Mesothelin-specific T cell responses are significantly expanded in cancer patients (p?=?0.0053), (b) the multifunctional CD4+ T cell response is directed toward a broad repertoire of epitopes within the Mesothelin protein. (c) Mesothelin-specific CD4+ T cell response is directly inhibited by elevated IL-10 in cancer patients. These data provides evidence for the use of Mesothelin as an immunogen for tumour-specific T cell response.
Chen, Yuan; Ayaru, Lakshmana; Mathew, Sanju; Morris, Emma
Acute pancreatitis and obstructive jaundice as initial complaints of hepatocellular carcinoma: case report
Background Patients with cirrhosis-associated hepatocellular carcinoma (HCC) rarely present with acute pancreatitis (AP) and obstructive jaundice as the main clinical features. AP with obstructive jaundice caused by common bile duct embolism (CBDE) is very rare. Case presentation A 54-year-old man with CBDE was misdiagnosed with common bile duct stones three times over a 7-month period. Investigations during this time did not identify CBDE. Surgical exploration was performed because of AP, obstructive jaundice, and a tumor in the left lobe of the liver. CBDE from the hepatic tumor was diagnosed by intraoperative biopsy and frozen section examination. The patient underwent left hemihepatectomy, cholecystectomy, and bile duct exploration. Conclusion Preoperative diagnosis of CBDE is difficult because of the rarity of the condition, lack of physician awareness, and easy misdiagnosis on imaging examinations. Early and accurate diagnosis of this condition is important.
High-dose lanreotide in the treatment of poorly differentiated pancreatic neuroendocrine carcinoma: a case report.
Pancreatic neuroendocrine tumors (NETs), including poorly differentiated carcinomas (NECs), are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs) have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel(�). In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0). Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days) contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs. PMID:24707264
Van Fraeyenhove, Frank; Meireson, Nathalie; Terriere, Luc; Willemsen, Paul; Kunnen, Jan; Mattelaer, Caroline; Van Acker, Frank; Schrijvers, Dirk
Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma
Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.
Ikeda, O., E-mail: firstname.lastname@example.com; Kusunoki, S.; Kudoh, K. [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Diagnostic Radiology (Japan); Takamori, H.; Tsuji, T.; Kanemitsu, K. [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Gastroenterological Surgery (Japan); Yamashita, Y. [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Diagnostic Radiology (Japan)
Bioengineered Human Arginase I with Enhanced Activity and Stability Controls Hepatocellular and Pancreatic Carcinoma Xenografts1
Hepatocellular carcinoma (HCC) and pancreatic carcinoma (PC) cells often have inherent urea cycle defects rendering them auxotrophic for the amino acid l-arginine (l-arg). Most HCC and PC require extracellular sources of l-arg and undergo cell cycle arrest and apoptosis when l-arg is restricted. Systemic, enzyme-mediated depletion of l-arg has been investigated in mouse models and human trials. Non-human enzymes elicit neutralizing antibodies, whereas human arginases display poor pharmacological properties in serum. Co2+ substitution of the Mn2+ metal cofactor in human arginase I (Co-hArgI) was shown to confer more than 10-fold higher catalytic activity (kcat/Km) and 5-fold greater stability. We hypothesized that the Co-hArgI enzyme would decrease tumor burden by systemic elimination of l-arg in a murine model. Co-hArgI was conjugated to 5-kDa PEG (Co-hArgI-PEG) to enhance circulation persistence. It was used as monotherapy for HCC and PC in vitro and in vivo murine xenografts. The mechanism of cell death was also investigated. Weekly treatment of 8 mg/kg Co-hArgI-PEG effectively controlled human HepG2 (HCC) and Panc-1 (PC) tumor xenografts (P = .001 and P = .03, respectively). Both cell lines underwent apoptosis in vitro with significant increased expression of activated caspase-3 (P < .001). Furthermore, there was evidence of autophagy in vitro and in vivo. We have demonstrated that Co-hArgI-PEG is effective at controlling two types of l-arg-dependent carcinomas. Being a nonessential amino acid, arginine deprivation therapy through Co-hArgI-PEG holds promise as a new therapy in the treatment of HCC and PC.
Glazer, Evan S; Stone, Everett M; Zhu, Cihui; Massey, Katherine L; Hamir, Amir N; Curley, Steven A
Requirement of nuclear factor ?B for Smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis.
Defects in apoptosis contribute to treatment resistance and poor outcome of pancreatic cancer, calling for novel therapeutic strategies. Here, we provide the first evidence that nuclear factor (NF) ?B is required for Smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis. The Smac mimetic BV6 cooperates with gemcitabine to reduce cell viability and to induce apoptosis. In addition, BV6 significantly enhances the cytotoxicity of several anticancer drugs against pancreatic carcinoma cells, including doxorubicin, cisplatin, and 5-fluorouracil. Molecular studies reveal that BV6 stimulates NF-?B activation, which is further increased in the presence of gemcitabine. Importantly, inhibition of NF-?B by overexpression of the dominant-negative I?B? superrepressor significantly decreases BV6- and gemcitabine-induced apoptosis, demonstrating that NF-?B exerts a proapoptotic function in this model of apoptosis. In support of this notion, inhibition of tumor necrosis factor ? (TNF?) by the TNF? blocking antibody Enbrel reduces BV6- and gemcitabine-induced activation of caspase 8 and 3, loss of mitochondrial membrane potential, and apoptosis. By demonstrating that BV6 and gemcitabine trigger a NF-?B-dependent, TNF?-mediated loop to activate apoptosis signaling pathways and caspase-dependent apoptotic cell death, our findings have important implications for the development of Smac mimetic-based combination protocols in the treatment of pancreatic cancer. PMID:22241962
Stadel, Dominic; Cristofanon, Silvia; Abhari, Behnaz Ahangarian; Deshayes, Kurt; Zobel, Kerry; Vucic, Domagoj; Debatin, Klaus-Michael; Fulda, Simone
Pancreatic tuberculosis or autoimmune pancreatitis.
Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis. PMID:24839445
Salahuddin, Ayesha; Saif, Muhammad Wasif
Pancreatic Tuberculosis or Autoimmune Pancreatitis
Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.
Saif, Muhammad Wasif
Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane.
We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta 1 and alpha 3 integrin subunits and laminin alpha 3 chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha 6 integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due to an abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha 3 beta 1 integrin receptor recognizing laminin-5. Images Figure 1 Figure 2 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10
Tani, T.; Lumme, A.; Linnala, A.; Kivilaakso, E.; Kiviluoto, T.; Burgeson, R. E.; Kangas, L.; Leivo, I.; Virtanen, I.
Depression and pancreatic cancer
Although pancreatic carcinoma and depression have been linked for years, the prevalence and relationship of these often coexisting diseases are still poorly understood. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. If the definition of depression is broadened
A. D. Boyd; M. Riba
Identification and Characterization of Poorly Differentiated Invasive Carcinomas in a Mouse Model of Pancreatic Neuroendocrine Tumorigenesis
Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understood. In this study we have identified and characterized a previously undescribed class of poorly differentiated PanNETs in the RIP1-Tag2 mouse model. We found that while the majority of tumors in the RIP1-Tag2 model are well-differentiated insulinomas, a subset of tumors had lost multiple markers of beta-cell differentiation and were highly invasive, leading us to term them poorly differentiated invasive carcinomas (PDICs). In addition, we found that these tumors exhibited a high mitotic index, resembling poorly differentiated (PD)-PanNETs in human patients. Interestingly, we identified expression of Id1, an inhibitor of DNA binding gene, and a regulator of differentiation, specifically in PDIC tumor cells by histological analysis. The identification of PDICs in this mouse model provides a unique opportunity to study the pathology and molecular characteristics of PD-PanNETs.
Hunter, Karen E.; Quick, Marsha L.; Sadanandam, Anguraj; Hanahan, Douglas; Joyce, Johanna A.
Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells.
Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2-5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2 and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 �l water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness. PMID:23475945
Kaur, Manjinder; Deep, Gagan; Jain, Anil K; Raina, Komal; Agarwal, Chapla; Wempe, Michael F; Agarwal, Rajesh
Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells
Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2�5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2 and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 �l water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness.
Agarwal, Rajesh
Metaplastic breast carcinoma: clinical�pathologic characteristics and HER2\\/neu expression
Background. Metaplastic breast carcinomas (MBC) are rare primary breast malignancies characterized by the co-existence of carcinoma with non-epithelial cellular elements. They can be classified as monophasic spindle cell (sarcomatoid) carcinoma, biphasic carcinosarcoma, adenocarcinoma with divergent stromal differentiation (osseous, chondroid and rarely rhabdoid) as well as adenosquamous and pure squamous cell carcinomas. There is a paucity of information on clinically relevant
P. J. Barnes; R. Boutilier; D. Chiasson; D. Rayson
Co-expression of CD133, CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.
The metastasis-related molecules CD133, CD44v6 and human tissue factor (TF) have been shown to be associated with tumor invasion and metastasis. This study aimed to determine whether co-expression of these three molecules was associated with metastasis and overall prognosis in pancreatic carcinoma. We analyzed the expression profiles of these three molecules by immunohistochemistry and evaluated the relationship of their expression profiles with metastasis and prognosis in 109 pancreatic carcinomas. The results showed that the expression levels of CD133, CD44v6 and TF were increased in pancreatic carcinoma. Co-expression of CD133, CD44v6 and TF (tri-expression) was also detected in pancreatic carcinoma. Clinical analysis showed that individual expression of CD133, CD44v6 or TF was associated with vessel invasion, lymph node metastasis and liver metastasis, while tri-expression was associated with lymph node metastasis. Survival analysis showed that patients with co-expression of CD133 and TF or tri-expression had lower and the lowest overall survival rates, respectively. Univariate analysis showed that T-factor, lymph node metastasis, TNM stage, and individual levels or tri-expression of CD133, CD44v6 and TF were survival risk factors. Multivariate analysis showed that tri-expression of CD133, CD44v6 and TF was an independent predictor of survival. These results suggest that overexpression of CD133, CD44v6 and TF is associated with pancreatic carcinoma metastasis. Tri-expression of these three molecules may be a useful predictor for pancreatic carcinoma prognosis. PMID:24920554
Chen, Kai; Li, Zhonghu; Jiang, Peng; Zhang, Xi; Zhang, Yujun; Jiang, Yan; He, Yu; Li, Xiaowu
FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: A meta-analysis
AIM: To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC). METHODS: A systematic review of relevant literatures in PubMed, Embase and Cochrane Library was performed. The sensitivity and specificity of diagnostic and staging studies, and HRs for prognosis predicting studies were pooled. The bivariate model was used for diagnostic studies and the random-effect model for prognostic studies. Heterogeneity between included studies was tested using ?2 test, and subgroup analysis was performed to explain the heterogeneities. All of the calculations were performed using Stata version 11.0. RESULTS: A total of 39 studies were included. The pooled sensitivity of PET in diagnosing PC (30 studies, 1582 patients), evaluating N stating (4 studies, 101 patients) and liver metastasis (7 studies, 316 patients) were 0.91 (95%CI: 0.88-0.93), 0.64 (95%CI: 0.50-0.76), and 0.67 (95%CI: 0.52-0.79), respectively; and the corresponding specificity was 0.81 (95%CI: 0.75-0.85), 0.81 (95%CI: 0.25-0.85), and 0.96 (95%CI: 0.89-0.98), respectively. In prognosis analysis (6 studies, 198 patients), significant difference of overall survival was observed between high and low standardized uptake value groups (HR = 2.39, 95%CI: 1.57-3.63). Subgroup analysis showed that PET/CT was more sensitive than PET alone in evaluating liver metastasis of PC, 0.82 (95%CI: 0.48-0.98) and 0.67 (95%CI: 0.52-0.79), respectively. CONCLUSION: PET can be used as a valuable diagnostic and predictive tool for PC, but its effect in the staging of PC remains indeterminate.
Wang, Zhen; Chen, Jun-Qiang; Liu, Jin-Lu; Qin, Xin-Gan; Huang, Yuan
Magnetic resonance imaging with magnetic resonance cholangiopancreatography accurately predicts resectability of pancreatic carcinoma
Accurate preoperative staging of pancreatic malignancy aids in directing appropriate therapy and avoids unnecessary invasive\\u000a procedures. We evaluated the accuracy of magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography\\u000a (MRCP) in determining resectability of pancreatic malignancy. Twenty-one patients with suspected pancreatic malignancy underwent\\u000a dynamic, contrast-en-hanced breath-hold MRI with MRCP prior to surgical evaluation. Results of this study were correlated\\u000a with
Steven N. Hochwald; Neil M. Rofsky; Michael Dobryansky; Peter Shamamian; Stuart G. Marais
Gene Expression Profiling of Microdissected Pancreatic Ductal Carcinomas Using High-Density DNA Microarrays
Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy-related death and is the eighth most common cancer with the lowest overall 5-year relative survival rate. To identify new molecular markers and candidates for new therapeutic regimens, we investigated the gene expression profile of microdissected cells from 11 normal pancreatic ducts, 14 samples of PDAC, and 4 well-characterized pancreatic cancer
Robert Gr�tzmann; Christian Pilarsky; Ole Ammerpohl; Jutta L�ttges; Armin B�hme; Bence Sipos; Melanie Foerder; Ingo Alldinger; Beatrix Jahnke; Hans Konrad Schackert; Holger Kalthoff; Bernd Kremer; G�nter Kl�ppel; Hans Detlev Saeger
Influence of MRE11, RAD50 and NIBRIN protein expression on survival in pancreatic carcinoma after curative resection.
The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand breaks, could serve as an early marker for new lesions in pancreatic cancer. We determined the expression of MRE11, RAD50 and NIBRIN, and their possible prognostic value regarding survival. Forty-one patients with ductal adenocarcinoma of the pancreas were included. All underwent curative surgery. Immunohistochemistry was performed for MRE11, RAD50 and NIBRIN. Subsequent analyses were based on a modified immunoreactive score. Statistical analysis was conducted using the statistics program "R". The mean follow-up period was 509 days. The mean age of the patients was 67�8 years, male=56%, female=44%. Eighty-seven percent underwent a Kausch-Whipple procedure, whereas a left side resection was performed in 22% of patients. Positive lymph nodes were found in 80% of cases, and patients were staged UICC IIa (12%), IIb (56%) and IV (29%). Overall significant results were found for MRE11 (p=0.02) and NIBRIN (p=0.01) expression and postoperative survival. We found a significant relation between the expression of MRE11, NIBRIN and the postoperative survival of patients with ductal adenocarcinoma. The link between the expression of the MRN complex, ATM and pancreatic cancer can be used to develop new treatment options for pancreatic carcinoma. PMID:23954013
Horst, Klemens; Ganzera, Silke; Kaisers, Wolfgang; Munding, Johanna; Flott-Rahmel, Berenike; Tannapfel, Andrea; Zirngibl, Hubert
Successful management of metachronous liver metastasis after pancreaticoduodectomy for pancreatic ductal carcinoma using hepatectomy and chemotherapy: a case report.
A 63-year-old woman was admitted to our Hospital for treatment of pancreatic head ductal carcinoma, and underwent pancreaticoduodedectomy (PD) in October 2007. At one month after surgery, she received systemic adjuvant chemotherapy using S-1 for three months. Because the serum carbohydrate antigen 19-9 (CA19-9) value was elevated at 23 months after surgery, the patient underwent systemic chemotherapy using gemcitabine. The serum CA19-9 decreased, but abdominal Computed Tomography (CT) revealed a hepatic metastasis in the ventrolateral segment of left hepatic lobe at 28 months after surgery. The chemotherapy was changed to oral S-1. At 35 months after surgery, abdominal CT revealed reduction of liver metastasis and that the serum CA19-9 was normalized, but chemotherapy had to be withdrawn because of severe myelosuppression. Because of her good general condition, the patient underwent partial hepatectomy for the liver metastasis. Histopathological examination demonstrated a complete response. Thirty six months after hepatectomy and 6 years after PD, the patient remains well without recurrence. We herein report a case of successful treatment for metachronous liver metastasis from pancreatic ductal carcinoma after PD by chemotherapy and hepatectomy and review the current literature. PMID:24778053
Iida, Tomonori; Nakabayashi, Yukio; Okui, Norimitsu; Shiba, Hiroaki; Otsuka, Masahiko; Yanaga, Katsuhiko
Adenoviral p53 gene transfer and gemcitabine in three patients with liver metastases due to advanced pancreatic carcinoma
Background. Current therapies for adenocarcinoma of the pancreas do not improve the life expectancy of patients. Methods. In a non-randomized pilot trail we tested whether a local therapy based upon an adenoviral gene transfer of wild type p53 in combination with gemcitabine administration would be safe in patients with liver metastases due to pancreatic carcinoma. We report on the clinical course of three patients with respect to safety, tolerability and tumor response. Results. Transient grade III toxicities occurred with fever, leucopenia, elevation of AP, ALT, AST, GGT, while grade IV toxicity occurred for bilirubin only. Laboratory tests suggested disseminated intravascular coagulation in all three patients, but fine needle biopsies of liver did not show any histological evidence of thrombus or clot formation. Progression of liver metastases was documented in one and stable disease in another patient two months after treatment. However, a major improvement with regression of the indexed lesion by 80% occurred in a third patient after a single administration of 7.5�1012 viral particles, and time to progression was extended to six months. Conclusion. The combination therapy of viral gene transfer and chemotherapy temporarily controls and diminishes tumor burden. Improvement of the toxicity profile is necessary. Further trials are warranted to improve treatment and life expectancy of patients suffering from fatal diseases such as pancreatic carcinoma.
Thiede, Christian; Fischer, Rainer; Ehninger, Gerhard; Haag, Cornelie
Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma
Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median {+-} SD, 16.0 {+-} 3.7 vs. 8.0 {+-} 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced pancreatic cancer, CTAI with systemic chemotherapy appeared to be effective and may prolong their survival. The development of a reservoir port system allowing for the homogeneous distribution of anticancer drugs is necessary to improve the prognosis of patients with advanced pancreatic cancer.
Ikeda, Osama, E-mail: firstname.lastname@example.com; Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Diagnostic Radiology (Japan); Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Gastroenterological Surgery (Japan)
Adjuvant Chemoradiotherapy After Pancreatic Resection for Invasive Carcinoma Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas
Purpose: Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. Methods and Materials: Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. Results: The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. Conclusion: Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.
Swartz, Michael J.; Hsu, Charles C. [Department of Radiation Oncology and Molecular Radiation Sciences, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Pawlik, Timothy M.; Winter, Jordan [Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Hruban, Ralph H.; Guler, Mehmet [Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Schulick, Richard D.; Cameron, John L. [Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Laheru, Daniel A. [Department of Medical Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Wolfgang, Christopher L. [Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Herman, Joseph M., E-mail: email@example.com [Department of Radiation Oncology and Molecular Radiation Sciences, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States)
Individual in-vitro sensitivities of human pancreatic carcinoma cell lines to photodynamic therapy
NASA Astrophysics Data System (ADS)
Photodynamic therapy (PDT) is a promising alternative in the treatment of pancreatic cancer in man, due to the low sensitivity of the normal pancreas to PDT as shown in preclinical studies. Investigations on four human pancreatic cancer lines (MIA PaCa-2, PaCa 1, PaCa 3, and CAPAN 2) in vitro demonstrated a considerable variety in PDT-sensitivity proportional to the degree of differentiation, which was related to photosensitizer-uptake (PhotofrinTM). The well differentiated pancreatic tumor line Capan 2 showed a close relationship between high cell density and increased PDT-resistance. The Photofrin uptake of Capan 2 at high cell densities could be increased by short trypsinization prior to photosensitizer exposure. The data supports the hypothesis that a complex intercellular organization reduces the cell surface available for photosensitizer uptake and may cause the relative PDT resistance of normal pancreatic tissues and highly differentiated tumors.
Moesta, K. Thomas; Dmytrijuk, Andrew; Schlag, Peter M.; Mang, Thomas S.
Endocrine-responsive Pancreatic Carcinoma: Steroid Binding and Cytotoxicity Studies in Human Tumor Cell Lines1
We have begun to investígate the steroid responsiveness of pancreatic cancer by comparing human (MiaPaCa, Colo-357, RWP-1, RWP-2) and rodent (AR42J) pancreatic tumor cell lines with cultured estrogen recep tor-positive breast cancer cells (MCF-7, T47-D). The four human pan creatic tumors contain measurable levels of specific estradio! binding sites with dissociation constants (A\\
Chris Benz; Charlene Hollander; Becky Miller
An Epithelial Cell Adhesion Molecule- and CD3-Bispecific Antibody Plus Activated T-Cells Can Eradicate Chemoresistant Cancer Stem-like Pancreatic Carcinoma Cells In Vitro.
Cancer stem-like properties of various types of cancer, including pancreatic cancer, one of the most aggressive types, correlate with metastasis, invasion, and therapeutic resistance. More importantly, chemoresistance in cancer stem-like cells (CSLCs) is a critical problem for eradication of pancreatic cancer. Several cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM), are molecular targets on CSLCs of pancreatic carcinoma. In this study, we investigated whether catumaxomab, a clinical-grade bi-specific antibody that binds to both EpCAM on tumor cells and CD3 on T-cells, combined with activated T-cells can eliminate chemoresistant pancreatic CSLCs in vitro. Firstly, we established a CSLC line (MU-PK1) from human pancreatic carcinoma cells derived from a patient with chemoresistant and disseminated pancreatic cancer. These CSLCs were almost completely resistant to gemcitabine-mediated cytotoxicity up to a concentration of 10 ?g/ml. The cells expressed high levels of CSLC markers (CD44 and EpCAM) and had significantly higher capacities for sphere formation, invasion, and aldehyde dehydrogenase-1 expression, which are associated with cancer stemness properties. We found that pre-treatment with catumaxomab and subsequent addition of interleukin-2/OKT3 activated autologous T-cells eliminated CSLCs during a short incubation period. Moreover, when MU-PK1 cells were cultured under hypoxic conditions, the CSLCs became more aggressive. However, the combination of cytokine-activated killer T-cells with catumaxomab successfully lysed almost all these cells. In conclusion, catumaxomab combined with activated T-cells may be a potent therapeutic modality to eradicate chemoresistant pancreatic CSLCs. PMID:25075094
Umebayashi, Masayo; Kiyota, Akifumi; Koya, Norihiro; Tanaka, Hiroto; Onishi, Hideya; Katano, Mitsuo; Morisaki, Takashi
Depletion of RhoGDI2 expression inhibits the ability of invasion and migration in pancreatic carcinoma.
Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of tumor metastasis, although its role in tumor progression remains controversial. In this study, we examined the expression of RhoGDI2 in PC tissues and cell lines. To investigate the function of RhoGDI2 in PC cells, RhoGDI2 expression was depleted in PANC-1 and Patu8988 cells by small interfering RNA (siRNA). RhoGDI2 was found to be overexpressed in pancreatic carcinoma (PC) tissues and PC cell lines. Additionally, the results showed that depletion of RhoGDI2 significantly inhibited cell motility and invasion in vitro, but did not affect cell proliferation. The clinical study together with the experimental data confirmed that RhoGDI2 modulated the expression of matrix metalloproteinase 2 (MMP2). Taken together, findings of the present study indicated that RhoGDI2 is involved in pancreatic tumor malignancy and metastasis. Thus, RhoGDI2 is a potential target for the gene therapy of PC. PMID:24788627
Yi, Bin; Hu, You; Qin, Gongzhao; Gu, Wen; Zhu, Xinguo; He, Songbing; Zhou, Jian; Li, Dechun
Evaluation of new anticancer agents against the MIA PaCa-2 and PANC-1 human pancreatic carcinoma xenografts.
Human pancreatic carcinoma xenograft models were developed from established MIA PaCa-2 and PANC-1 cell lines (ATCC, Rockville, MD). Tumors were maintained by serial trocar implantation in CD1 nu/nu mice, and attempts were made to test all drugs under optimal schedules at maximum tolerated doses. In both models, adriamycin, cisplatin, and 5-fluorouracil were inactive (< 60% inhibition of tumor weight), whereas gemcitabine (LY188011] produced modest activity (69% inhibition in MIA PaCa-2 and 76% inhibition in PANC-1. Major differences in tumor sensitivity were noted with diarylsulfonylureas (DSU) and taxol. The DSU (Sulofenur [LY186641] and LY295501) produced complete inhibition in the MIA PaCa-2 xenograft, but were inactive in PANC-1. Conversely, taxol produced 80% inhibition of PANC-1 tumor growth, but was inactive against MIA PaCa-2. In general, in vivo antitumor activity roughly correlated with in vitro tumor cytotoxicity with the exception of DSU. We have previously shown that DSU are extensively bound to albumin and that in vitro cytotoxic activity in serum-containing medium is not predictive of in vivo antitumor activity. The MIA PaCa-2 and PANC-1 xenograft models may be useful for selecting potential candidates for therapy of human pancreatic cancer. PMID:8123942
Schultz, R M; Merriman, R L; Toth, J E; Zimmermann, J E; Hertel, L W; Andis, S L; Dudley, D E; Rutherford, P G; Tanzer, L R; Grindey, G B
Adjuvant Treatment of Pancreatic Carcinoma in a Clinically Adapted Mouse Resection Model
Background: The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model. Methods: Subtotal pancreatectomy in mice was performed after
Juergen Tepel; Marie-Luise Kruse; Matthias Kapischke; Sieglinde Haye; Bence Sipos; Bernd Kremer; Holger Kalthoff
[Interstitial radiotherapy with 125I in non-resectable pancreatic carcinoma].
The authors analyze results of 220 patients suffering from pancreatic cancer treated in their department from 1982 to 1992. Among these patients 24 of them underwent surgical operation for positioning of radioactive pills. The discussion is on indication and results of this technique, considering also what's reported in scientific literature on the argument. PMID:7617264
Arcuri, V; Tommasi, G V; Casolino, V; Ceppa, P; Colacino, R; Valente, U
RhoC Interacts with Integrin ?5?1 and Enhances Its Trafficking in Migrating Pancreatic Carcinoma Cells
Human pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic dissemination. Although RhoC has been implicated in cancer cell migration, the relevant underlying molecular mechanisms remain unknown. RhoC has been implicated in the enhancement of cancer cell migration and invasion, with actions which are distinct from RhoA (84% homology), and are possibly attributed to the divergent C-terminus domain. Here, we confirm that RhoC significantly enhances the migratory and invasive properties of pancreatic carcinoma cells. In addition, we show that RhoC over-expression decreases cancer cell adhesion and, in turn, accelerates cellular body movement and focal adhesion turnover, especially, on fibronectin-coated surfaces. Whilst RhoC over-expression did not alter integrin expression patterns, we show that it enhanced integrin ?5?1 internalization and re-cycling (trafficking), an effect that was dependent specifically on the C-terminus (180-193 amino acids) of RhoC protein. We also report that RhoC and integrin ?5?1 co-localize within the peri-nuclear region of pancreatic tumor cells, and by masking the CAAX motif at the C-terminal of RhoC protein, we were able to abolish this interaction in vitro and in vivo. Co-localization of integrin ?5?1 and RhoC was demonstrable in invading cancer cells in 3D-organotypic cultures, and further mimicked in vivo analyses of, spontaneous human, (two distinct sources: operated patients and rapid autopsy programme) and transgenic murine (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), pancreatic cancers. In both cases, co-localization of integrin ?5?1 and RhoC correlated with poor differentiation status and metastatic potential. We propose that RhoC facilitates tumor cell invasion and promotes subsequent metastasis, in part, by enhancing integrin ?5?1 trafficking. Thus, RhoC may serve as a biomarker and a therapeutic target.
Davies, Derek; Yu, Yongwei; Frese, Kristopher; Froeling, Fieke E. M.; Woolf, Adam K.; Feakins, Roger M.; Naito, Yoshiki; Iacobuzio-Donahue, Christine; Tuveson, David A.; Hart, Ian R.; Kocher, Hemant M.
Pancreatic carcinoma cells are susceptible to non-invasive radiofrequency fields after treatment with targeted gold nanoparticles
Background Gold and carbon nanoparticles absorb non-ionizing radiofrequency (RF) energy and release heat. Solid gold nanoparticles are delivered to cancer cells via conjugation with targeting antibodies. Here, 20 nm gold particles were conjugated to cetuximab, an epidermal growth factor recpetor-1 (EGFR-1) antibody. Methods A pancreatic carcinoma cell line that highly expresses EGFR-1, Panc-1, and a breast carcinoma cell line that minimally expresses EGFR-1, Cama-1, were treated with 100 nM cetuximab-conjugated gold nanoparticles for 3 hours (n = 4). Thirty-six hours later, the dishes were placed in an RF field with a generator power of 200 W for 5 minutes. After another 36 hours, cell injury and death were evaluated with flow cytometry. Results The targeted cell line, Panc-1, had a viability of 45.5% � 11.7% while Cama-1 cell had a viability of 91.7% � 1.6% after RF field exposure (p < 0.008). Transmission electron microscopy showed gold nanoparticle uptake in Panc-1 cells, but negligible uptake by Cama-1 cells. Non-targeted cells do not internalize a sufficient amount of antibody-conjugated gold nanoparticles to induce injury in a noninvasive RF field. Conclusion This technique could be useful in cancer treatment provided a cancer-specific antibody is utilized to localize gold nanoparticles to malignant cells.
Glazer, E. S.; Massey, K. L.; Zhu, C.; Curley, S. A.
Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma.
Urokinase plasminogen activator (uPA) is a serine proteinase that has been suggested to play an important role in cancer invasion and metastasis. It binds to a specific membrane receptor denominated uPA receptor (uPAR). uPA activates plasminogen to form plasmin, which participates in tissue degradation and proteolysis. Binding of uPA to its receptor accelerates UPA's own activation from pro-uPA, enhancing the activity of the uPA/uPAR cascade. Using immunohistochemistry and Northern blot analysis, we analysed the role of uPA and uPAR in 30 human pancreatic cancers. Immunohistochemical analysis demonstrated moderate to strong immunostaining of both factors in most pancreatic cancers. Cancer lesions with signs of invasion exhibited the strongest immunohistochemical signals for both factors. In addition, in desmoplastic areas adjacent to the cancer cells, moderate uPA and uPAR immunoreactivity was detectable. Northern blot analysis revealed a sixfold and a fourfold increase in uPA and uPAR mRNA levels in pancreatic cancer, respectively, in comparison with normal controls (P<0.01). Correlation of the Northern blot data with the clinical parameters of the patients indicated that patients with concomitant overexpression of uPA and uPAR had a shorter post-operative survival (median 9 months; mean+/-s.d. 10.2+/-3.6 months) than patients in whom only one or none of these factors were overexpressed (median 18 months; mean+/-s.d. 20.3+/-8.7 months) (P<0.002). Our data suggest that uPA and uPAR may serve as prognostic markers in human pancreatic cancer and that the marked overexpression of both factors may create an environment that enables pancreatic cancer cells to invade surrounding tissues. Images Figure 1 Figure 2 Figure 3 Figure 4
Cantero, D.; Friess, H.; Deflorin, J.; Zimmermann, A.; Brundler, M. A.; Riesle, E.; Korc, M.; Buchler, M. W.
Late presentation of a mucinous ovarian adenocarcinoma which was initially diagnosed as a primary pancreatic carcinoma: a case report and review of the literature
Introduction Adenocarcinoma of the ovary is an aggressive neoplasm which often metastasizes to the lung or liver. Metastases rarely occur to the pancreas, but a tissue diagnosis is required to confirm this event. Although most tumors of the pancreas are primary pancreatic neoplasms, metastatic lesions have been reported most commonly as arising from renal cell carcinoma. Case presentation We report the case of a 51-year-old Caucasian woman with ovarian mucinous adenocarcinoma with metastasis to the head of the pancreas that was originally misdiagnosed as a pancreatic primary tumor. Conclusion Mucinous ovarian adenocarcinomas rarely metastasize to the pancreas. New pancreatic lesions should be investigated through tissue biopsy and tumor markers, while keeping an open-minded differential diagnosis to avoid a misdiagnosis or a delay in treatment.
Metastatic hepatocellular carcinoma presenting as a pancreatic mass by computed tomography scan and mimicking a primary neuroendocrine tumor: a potential pitfall in aspiration cytology.
Hepatocellular carcinoma (HCC) is a highly malignant neoplasm, often presenting at late stage and portending a poor prognosis for the patient. The peripancreatic fat is a rare site of extrahepatic metastasis, and metastatic HCC can mimic primary pancreatic neoplasms, even in this location. It is crucial to be aware of this pitfall in the evaluation of aspiration cytology of pancreatic neoplasms and to develop a strategy to reach the correct diagnosis. We present an endoscopic ultrasound fine-needle aspiration diagnosis of metastatic HCC presenting as a pancreatic mass radiologically that had neuroendocrine features on various cytological and histological preparations. The metastatic lesions were located surgically in the peripancreatic adipose tissue with involvement of one peripancreatic lymph node. This case illustrates the utility of FNA for diagnosing uncommon presentations of HCC and the importance of clinical history, cell block, and an immunocytochemical panel in determining the origin of the tumor. PMID:19582809
Fitzhugh, Valerie A; Kim, Stacey A; Borcich, Anthony; Zhu, Hongfa; Wu, Maoxin; Szporn, Arnold H; Chen, Hua
Requirement of Nuclear Factor ?B for Smac Mimetic-Mediated Sensitization of Pancreatic Carcinoma Cells for Gemcitabine-Induced Apoptosis12
Defects in apoptosis contribute to treatment resistance and poor outcome of pancreatic cancer, calling for novel therapeutic strategies. Here, we provide the first evidence that nuclear factor (NF) ?B is required for Smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis. The Smac mimetic BV6 cooperates with gemcitabine to reduce cell viability and to induce apoptosis. In addition, BV6 significantly enhances the cytotoxicity of several anticancer drugs against pancreatic carcinoma cells, including doxorubicin, cisplatin, and 5-fluorouracil. Molecular studies reveal that BV6 stimulates NF-?B activation, which is further increased in the presence of gemcitabine. Importantly, inhibition of NF-?B by overexpression of the dominant-negative I?B? superrepressor significantly decreases BV6- and gemcitabine-induced apoptosis, demonstrating that NF-?B exerts a proapoptotic function in this model of apoptosis. In support of this notion, inhibition of tumor necrosis factor ? (TNF?) by the TNF? blocking antibody Enbrel reduces BV6- and gemcitabine-induced activation of caspase 8 and 3, loss of mitochondrial membrane potential, and apoptosis. By demonstrating that BV6 and gemcitabine trigger a NF-?B-dependent, TNF?-mediated loop to activate apoptosis signaling pathways and caspase-dependent apoptotic cell death, our findings have important implications for the development of Smac mimetic-based combination protocols in the treatment of pancreatic cancer.
Stadel, Dominic; Cristofanon, Silvia; Abhari, Behnaz Ahangarian; Deshayes, Kurt; Zobel, Kerry; Vucic, Domagoj; Debatin, Klaus-Michael; Fulda, Simone
Effects of a Non Thermal Plasma Treatment Alone or in Combination with Gemcitabine in a MIA PaCa2-luc Orthotopic Pancreatic Carcinoma Model
Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.
Brulle, Laura; Vandamme, Marc; Ries, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stephanie; Trichet, Valerie; Richard, Serge; Pouvesle, Jean-Michel; Le Pape, Alain
Multidisciplinary treatment with chemotherapy, targeted drug, and high-intensity focused ultrasound in advanced pancreatic carcinoma
This study reports a case of an advanced pancreatic cancer patient with liver metastasis who was treated with a combination\\u000a of chemotherapy, targeted drugs, and high-intensity focused ultrasound (HIFU). The abdominal pain was successfully relieved\\u000a after the HIFU therapy. The patient had an 18-month survival with satisfactory quality of life. Large-scale randomized clinical\\u000a trials are necessary to evaluate the long-term
Ying YuanHong; Hong Shen; Xiao-Ye Hu; Fei-Ying Gu; Mo-Dan Li; Xian Zhong
Therapeutic strategies for advanced neuroendocrine carcinomas of jejunum\\/ileum and pancreatic origin
Multimodal treatment options for advanced gastroenteropancreatic neuroendocrine tumours (NET) of jejunum\\/ileum and of pancreatic origin are reviewed. Current topics being discussed are: European Neuroendocrine Tumour Society 2006\\/7, American Joint Cancer Committee\\/Union Internationale Contre le Cancer 2009 and WHO 2010 recommendations for grading and staging of NET; surgery of the primary tumour in distant metastasised disease; surgery of metastatic liver disease
Christoph J Auernhammer; Burkhard G�ke
VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma.
Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31(+) vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis. PMID:18665180
Beckermann, B M; Kallifatidis, G; Groth, A; Frommhold, D; Apel, A; Mattern, J; Salnikov, A V; Moldenhauer, G; Wagner, W; Diehlmann, A; Saffrich, R; Schubert, M; Ho, A D; Giese, N; B�chler, M W; Friess, H; B�chler, P; Herr, I
VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma
Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31+ vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis.
Beckermann, B M; Kallifatidis, G; Groth, A; Frommhold, D; Apel, A; Mattern, J; Salnikov, A V; Moldenhauer, G; Wagner, W; Diehlmann, A; Saffrich, R; Schubert, M; Ho, A D; Giese, N; Buchler, M W; Friess, H; Buchler, P; Herr, I
Role of myofibroblasts in innate chemoresistance of pancreatic carcinoma--epigenetic downregulation of caspases.
We recently reported on continuous tumor-stroma interactions essentially contributing to chemoresistance of pancreatic ductal adenocarcinoma (PDAC) cells. As demonstrated here, long-term coculture with pancreatic myofibroblasts representing the main stromal compartment of PDAC resulted in a chemoresistant phenotype in the pancreatic ductal epithelial cell line H6c7 as well as in the chemosensitive PDAC cell line T3M4. This involved a reduced expression of caspases and the caspase inducing transcription factor STAT1, both caused by diminished gene transcription. The DNA-methylation inhibitor 5-azadeoxycytidine enhanced caspase and STAT1 expression in cocultured H6c7 and T3M4 cells along with an increased chemosensitivity, indicating a role for CpG DNA-hypermethylation in the downregulation of these crucial apoptosis mediators. Cocultured H6c7 and T3M4 cells exhibited elevated nuclear levels of DNA-methyltransferase-1 (DNMT1). Silencing of DNMT1 expression by siRNA increased expression of caspases and STAT1 and restored chemosensitivity. In SCID mice, tumors arising from coinoculated T3M4 cells and myofibroblasts (co-tumors) responded less towards chemotherapy than mono-tumors, exhibiting decreased apoptosis, no remission and reduced expression of caspases and STAT1. These data underscore the role of myofibroblasts in chemoresistance of PDAC and point to the importance of caspases as central target structures of epigenetic regulation in this scenario. Furthermore, an activated microenvironment might apparently promote the manifestation of chemoresistance already in premalignant precursor cells at early stages of PDAC tumorigenesis. PMID:18649362
M�erk�ster, Susanne Sebens; Werbing, Veronika; Koch, Dorothee; Sipos, Bence; Ammerpohl, Ole; Kalthoff, Holger; Tsao, Ming-Sound; F�lsch, Ulrich R; Sch�fer, Heiner
Intraoperative Radiation Therapy in Resected Pancreatic Carcinoma: Long-Term Analysis
Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative 'flash' RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT ({approx}50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT)
Valentini, Vincenzo [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Morganti, Alessio G. [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Department of Radiotherapy, 'John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy); Macchia, Gabriella [Department of Radiotherapy, 'John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy)], E-mail: firstname.lastname@example.com; Mantini, Giovanna; Mattiucci, Gian C. [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Brizi, M. Gabriella [Department of Radiology, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Alfieri, Sergio; Bossola, Maurizio; Pacelli, Fabio [Department of Surgery, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Sofo, Luigi [Department of Surgery, 'John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy); Doglietto, Giovanbattista [Department of Surgery, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Cellini, Numa [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy)
Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood, bone marrow and peritoneal lavage of pancreatic carcinoma patients
AIM: To evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas. METHODS: Sixty-eight patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non-pancreatic benign surgical diseases (n = 15, control group) were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR. RESULTS: CK-19 mRNA expression was increased in 24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the patients with pancreatic cancer. In 15 (40%) of the patients with pancreatic cancer, disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3). Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancer patients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis. CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocar-cinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.
Hoffmann, Katrin; Kerner, Christiane; Wilfert, Wolfgang; Mueller, Marc; Thiery, Joachim; Hauss, Johann; Witzigmann, Helmut
Early experience of laparoscopic ultrasonography in the management of pancreatic carcinoma
A 7.5-MHz linear array ultrasound probe has been developed for the evaluation of solid organs at laparoscopy. Twelve patients with suspected carcinoma of the head of the pancreas, considered at initial investigation to have resectable disease, were submitted to laparoscopy. In 4 patients, diagnostic laparoscopy revealed hepatic metastases (4 patients), peritoneal dissemination of tumor (2), and malignant ascites (1). Laparoscopic
Mahadaven Murugiah; Simon Paterson-Brown; John A. Windsor; W. F. Anthony Miles; O. James Garden
An in vitro model of pancreatic carcinoma. Morphology and in vivo growth.
Pancreas rudiments from 13-day rat embryos were cultured in the presence of dimethylnitrosamine (DMN) for up to 10 weeks. Pancreas morphogenesis and differentiation occurred during the first week of culture. Acinar cell degeneration and necrosis began on the fifth day of culture and resulted in almost complete loss of acinar cells, islet cells, and fibroblasts by the end of the third week. This was associated with proliferation of cells without zymogen granules (centroacinar, ductal, or undifferentiated?). Theses cells formed glandular structures which extended to the surface of the explant. By the end of the fourth week, explants resembled ductal hyperplasia with foci of carcinoma in situ. The distribution pattern of neoplasia in 343 explants examined after 10 weeks of DMN treatment was as follows: 79% resembled ductal cell carcinoma; 9%, ductal hyperplasia; and 3%, acinar cell carcinoma. Nude mice injected with cell suspensions prepared from 10-week-old culture developed subcutaneous nodules. These nodules resembled duct cell carcinoma with desmoplastic reaction. Images Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 1 Figure 2 Figure 3
Parsa, I.; Marsh, W. H.
KRAS mutant allele-specific imbalance is associated with worse prognosis in pancreatic cancer and progression to undifferentiated carcinoma of the pancreas.
KRAS codon 12 mutations are present in about 90% of ductal adenocarcinomas and in undifferentiated carcinomas of the pancreas. The role of KRAS copy number changes and resulting KRAS mutant allele-specific imbalance (MASI) in ductal adenocarcinoma (n=94), and its progression into undifferentiated carcinoma of the pancreas (n=25) was studied by direct sequencing and KRAS fluorescence in situ hybridization (FISH). Semi-quantitative evaluation of sequencing electropherograms showed KRAS MASI (ie, mutant allele peak higher than or equal to the wild-type allele peak) in 22 (18.4%) cases. KRAS FISH (performed on 45 cases) revealed a trend for more frequent KRAS amplification among cases with KRAS MASI (7/20, 35% vs 3/25, 12%, P=0.08). KRAS amplification by FISH was seen only in undifferentiated carcinomas (10/24, 42% vs 0/21 pancreatic ductal adenocarcinoma, 0%, P=0.0007). In 6 of 11 cases with both undifferentiated and well-differentiated components, transition to undifferentiated carcinoma was associated with an increase in KRAS copy number, due to amplification and/or chromosome 12 hyperploidy. Pancreatic carcinomas with KRAS MASI (compared to those without MASI) were predominantly undifferentiated (16/22, 73% vs 9/97, 9%, P<0.001), more likely to present at clinical stage IV (5/22, 23% vs 7/97, 7%, P=0.009), and were associated with shorter overall survival (9 months, 95% confidence interval, 5-13, vs 22 months, 95% confidence interval, 17-27; P=0.015) and shorter disease-free survival (5 months, 95% confidence interval, 2-8 vs 13 months, 95% confidence interval, 10-16; P=0.02). Our findings suggest that in a subset of ductal adenocarcinomas, KRAS MASI correlates with the progression to undifferentiated carcinoma of the pancreas. PMID:23599154
Krasinskas, Alyssa M; Moser, A James; Saka, Burcu; Adsay, N Volkan; Chiosea, Simion I
Liver metastases of pancreatic acinar cell carcinoma with marked nuclear atypia and pleomorphism diagnosed by EUS FNA cytology: a case report with emphasis on FNA cytological findings
Background Acinar cell carcinoma of the pancreas is a rare neoplasm. Although this tumor has been well characterized histologically, the morphological patterns in Fine Needle Aspiration Cytology have not been well defined. Unlike ductal adenocarcinomas, endocrine tumors, and solid pseudopapillary tumors of the pancreas with their characteristic FNA cytological features, acinar cell carcinomas pose a particular diagnostic challenge by sharing many cytomorphologic features with endocrine tumors of the pancreas. Case presentation A 37-year-old man presented with lower chest and left upper quadrant abdominal pain. Computed tomography revealed a 7.8 � 7.3 cm irregular, partially cystic mass in the body and tail of the pancreas, and two lesions in the liver compatible with metastases. Subsequently, the patient underwent endoscopic ultrasound-guided fine needle aspiration on one of the two metastatic liver masses. FNA cytology revealed abundant, loosely cohesive clusters of malignant epithelial cells with vaguely acinar and trabecular formations. The pleomorphic nuclei had fine granular chromatin and occasionally small nucleoli. There were scant to moderate amounts of cytoplasm. Scattered, strikingly large tumor cells with giant nuclei, prominent mitoses and associated necrosis were evident. A pancreatic endocrine tumor was suspected initially, but acinar cell carcinoma of the pancreas was confirmed by immunohistochemistry, cytochemical and ultrastructural studies. Conclusion We describe a case of pancreatic acinar cell carcinoma with unusual cytomorphologic features mimicking an endocrine tumor of pancreas, encountered in endoscopic ultrasound-guided fine needle aspiration of a metastatic liver mass and discuss the diagnostic approach for this unusual pancreatic tumor in fine needle aspiration cytology.
Peng, Hong Q; Darwin, Peter; Papadimitriou, John C; Drachenberg, Cinthia B
Imaging Findings Associated with Childhood Primary Intracranial Squamous Cell Carcinoma
Summary: A 5-year-old girl with no preexisting systemic or CNS neoplasm presented with a large right temporal mass lesion, the histopathology of which proved to be a poorly differentiated adenosquamous carcinoma, a highly unusual primary intracranial tumor. The tumor recurred despite radical resection, chemotherapy, and radiation therapy. Malignant transformation of benign intracranial dysembryogenetic tumors is known to occur infre- quently.
Rajan Jain; Sachin Gujar; Paul McKeever; Patricia Robertson; Suresh Mukherji
CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans
Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.
Beatty, Gregory L.; Chiorean, Elena G.; Fishman, Matthew P.; Saboury, Babak; Teitelbaum, Ursina R.; Sun, Weijing; Huhn, Richard D.; Song, Wenru; Li, Dongguang; Sharp, Leslie L.; Torigian, Drew A.; O'Dwyer, Peter J.; Vonderheide, Robert H.
Synchronous occurrence of carcinoid, signet-ring cell carcinoma and heterotopic pancreatic tissue in stomach: A case report and literature review.
We presented an unusual case with coexistence of carcinoid, signet-ring cell carcinoma (SRC) and heterotopic pancreatic tissue in stomach. Gastroscopic examination of this 63-year-old male patient showed multiple protrusions in gastric corpus near the greater curvature, identified by subsequent biopsy as carcinoid. Distal subtotal gastrectomy was performed. Histological and immunohistochemical examinations showed a carcinoid tumor in gastric corpus near the greater curvature, an intramucosal SRC at the lesser curvature of corpus and heterotopic pancreatic tissue in muscularis propria of the antrum at the lesser curvature with hyperplasia of peripheral endocrine cells producing multiple pancreatic hormones. We reviewed the literatures on clinicopathological characteristics and the differential diagnosis of the above three abnormalities, and concluded that the carcinoid in corpus near the greater curvature and SRC in the lesser curvature are independent lesions; the foci of endocrine cells in the muscularis propria and serosa are hyperplastic lesions from the heterotopic pancreatic tissue, rather than dissemination of carcinoid in corpus. PMID:17131492
Yang, Lin; Zhang, Hong-Tu; Zhang, Xun; Sun, Yun-Tian; Cao, Zhi; Su, Qin
Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma.
Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. Most drugs that pass preclinical tests fail in these patients, emphasizing the need of improved preclinical models to test novel anticancer strategies. Here, we developed four orthotopic mouse models using primary human PDAC cells genetically engineered to express firefly- and Gaussia luciferase, simplifying the ability to monitor tumor growth and metastasis longitudinally in individual animals with MRI and high-frequency ultrasound. In these models, we conducted detailed histopathologic and immunohistochemical analyses on paraffin-embedded pancreatic tissues and metastatic lesions in liver, lungs, and lymph nodes. Genetic characteristics were compared with the originator tumor and primary tumor cells using array-based comparative genomic hybridization, using frozen specimens obtained by laser microdissection. Notably, the orthotopic human xenografts in these models recapitulated the phenotype of human PDACs, including hypovascular and hypoxic areas. Pursuing genomic and immunohistochemical evidence revealed an increased copy number and overexpression of c-Met in one of the models; we examined the preclinical efficacy of c-Met inhibitors in vitro and in vivo. In particular, we found that crizotinib decreased tumor dimension, prolonged survival, and increased blood and tissue concentrations of gemcitabine, synergizing with a cytidine deaminase-mediated mechanism of action. Together, these more readily imaged orthotopic PDAC models displayed genetic, histopathologic, and metastatic features similar to their human tumors of origin. Moreover, their use pointed to c-Met as a candidate therapeutic target in PDAC and highlighted crizotinib and gemcitabine as a synergistic combination of drugs warranting clinical evaluation for PDAC treatment. PMID:24085787
Avan, Amir; Caretti, Viola; Funel, Niccola; Galvani, Elena; Maftouh, Mina; Honeywell, Richard J; Lagerweij, Tonny; Van Tellingen, Olaf; Campani, Daniela; Fuchs, Dieter; Verheul, Henk M; Schuurhuis, Gerrit-Jan; Boggi, Ugo; Peters, Godefridus J; W�rdinger, Thomas; Giovannetti, Elisa
Survivin and pancreatic cancer
Pancreatic cancer is estimated to be the fourth most common cancer in men and fifth in women in the world and has poor prognosis. In recent years, more and more effort has been put on the relationship between pancreatic cancer and apoptosis. As a newly discovered inhibitor of apoptosis, survivin has drawn more attention. Strong evidence has shown that survivin is expressed in pancreatic cancer cells on frozen sections. Survivin increases in the development of pancreatic ductal adenocarcinoma and its expression can be a marker in evaluating the prognosis of pancreatic cancer patients. Survivin itself may be a new target in the treatment of pancreatic cancer and a survivin DNA vaccine could generate specific antitumor effects in pancreatic carcinoma models.
Liu, Bin-Bin; Wang, Wei-Hong
Prolonged Clinical Benefit of Everolimus Therapy in the Management of High-Grade Pancreatic Neuroendocrine Carcinoma
Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.
Fonseca, Paula J.; Uriol, Esther; Galvan, Jose A.; Alvarez, Carlos; Perez, Quionia; Villanueva, Noemi; Berros, Jose P.; Izquierdo, Marta; Vieitez, Jose M.
Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010
Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.
Sharma, Chakshu; Eltawil, Karim M; Renfrew, Paul D; Walsh, Mark J; Molinari, Michele
Influence of interferon-? on the expression of the cancer stem cell markers in pancreatic carcinoma cells.
The cytokine interferon-? (IFN?) belongs to the group of type I interferons already used in cancer therapy. This drug possesses radio- and chemo-sensitizing, and shows anti-angiogenic properties. Cancer stem cells (CSC) are a unique population of tumor cells that initiate secondary tumors, and are responsible for metastasis formation. Patients with pancreatic ductal adenocarcinoma (PDAC) have an especially poor prognosis, with 5-year survival rates of only ~1% and median survival of 4-6 months. PDAC is characterized by the presence of CSC. In this work we demonstrate for the first time that IFN? up-regulates the expression of the CSC markers CD24, CD44 and CD133 in in vitro and in vivo models of PDAC. We showed the IFN? effects on the migration and invasion of PDAC cells, which is associated with the level of the CSC marker expression. In vivo, this drug inhibits tumor growth but promotes metastasis formation in the early stage of tumor growth. We propose that IFN? may enhance the enrichment of CSC in PDAC tumors. Additionally we also suggest that in combination therapy of solid tumors with IFN?, this drug should be given to patients prior to chemotherapy to achieve the CSC activation. PMID:24726912
Zhu, Yifan; Karakhanova, Svetlana; Huang, Xiaolun; Deng, Shao Ping; Werner, Jens; Bazhin, Alexandr V
Successful resection of pancreatic carcinoma recurrence in the remnant pancreas after a pancreaticoduodenectomy.
We present a rare case in which a pancreatectomy was performed for a recurrent tumor in the remnant pancreas after a pancreaticoduodenectomy, and we review the associated literature. A 67-year old man underwent pancreaticoduodenectomy for pancreatic cancer on April 9, 2003. The tumor was composed of well differentiated adenocarcinoma and diagnosed as R0, pT2, pN1, pM0, pStage III according to UICC TNM classification. Five years and eight months later, his serum level of carcinoembryonic antigen was found to be elevated, and a computed tomography showed a low-density mass near the site of the pancreaticojejunostomy and dilatation of the jejunal stump. We conducted a total resection of the remnant pancreas including pancreaticojejunostomy, splenectomy and peripancreatic lymph node dissection without any residual macroscopic tumor. Histologically, it was diagnosed as a well differentiated adenocarcinoma, similar to the initial tumor. It is difficult to assess whether this tumor developing in the remnant pancreas was a local recurrence or a second primary cancer. However, we believe this tumor was a second primary tumor because of the long interval period and the absence of a neoplastic invasion in the resection margins of the initial specimens. PMID:21937417
Kinoshita, Hiroyuki; Yamade, Naohisa; Nakai, Hiroaki; Sasaya, Takahiro; Matsumura, Shuichi; Kimura, Arishige; Shima, Koichi
Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group.
The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease. PMID:1657839
Tepper, J E; Noyes, D; Krall, J M; Sause, W T; Wolkov, H B; Dobelbower, R R; Thomson, J; Owens, J; Hanks, G E
Effective combination gene therapy using CEACAM6-shRNA and the fusion suicide gene yCDglyTK for pancreatic carcinoma in vitro.
The incidence of pancreatic carcinoma, a gastrointestinal malignancy, is on the increase and effective therapeutic strategies are therefore required. This study aimed to construct a recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK from CEACAM6 targeting shRNA and the fusion suicide gene yCDglyTK for inhibition of SW1990 human pancreatic carcinoma cell growth and invasion. A plasmid containing hU6 promoter and CEACAM6 targeting short hairpin RNA (CEACAM6-shRNA) frame was constructed. It was subcloned to a CEA promoter-driven fusion suicide gene pcDNA3.1(-)yCDglyTK. The recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK was identified by restriction endonuclease analysis and DNA sequencing. The recombinant plasmid was delivered into SW1990 human pancreatic carcinoma cells, the mRNA and protein expression of yCDglyTK and CEACAM6 was examined by RT-PCR, western blot analysis and immunofluorescence. SW1990 cells were treated with the prodrug 5-fluorocytosine (5-FC), and the cell viability was evaluated using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The invasiveness and migration of SW1990 cells were evaluated by transwell migration assays. The restriction endonuclease analysis and DNA sequencing confirmed the construction of the recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis outcomes showed that yCDglyTK was expressed in SW1990 cells and expression of CEACAM6 in SW1990 cells was significantly knocked down. MTT assay showed that the mean viability of SW1990 cells was significantly reduced after administration of the prodrug 5-FC in vitro. Transwell migration assays showed that invasion and migration action of SW1990 cells was significantly inhibited. In conclusion, recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK was successfully constructed. The recombinant plasmid may therefore serve as a novel gene therapy approach for pancreatic carcinoma. PMID:23251258
Long, Hongyu; Li, Qingfu; Wang, Yuan; Li, Qian; Liu, Ting; Peng, Jie
Expression of the CXCR6 on polymorphonuclear neutrophils in pancreatic carcinoma and in acute, localized bacterial infections
The chemokine receptor CXCR6 has been described on lymphoid cells and is thought to participate in the homing of activated T-cells to non-lymphoid tissue. We now provide evidence that the chemokine receptor CXCR6 is also expressed by activated polymorphonuclear neutrophils (PMN) in vivo: Examination of biopsies derived from patients with pancreatic carcinoma by confocal laser scan microscopy revealed a massive infiltration of PMN that expressed CXCR6, while PMN of the peripheral blood of these patients did not. To answer the question whether CXCR6 expression is a property of infiltrated and activated PMN, leucocytes were collected from patients with localized soft tissue infections in the course of the wound debridement. By cytofluorometry, the majority of these cells were identified as PMN. Up to 50% of these PMN were also positive for CXCR6. Again, PMN from the peripheral blood of these patients were nearly negative for CXCR6, as were PMN of healthy donors. In a series of in vitro experiments, up-regulation of CXCR6 on PMN of healthy donors by a variety of cytokines was tested. So far, a minor, although reproducible, effect of tumour necrosis factor (TNF?) was seen: brief exposure with low-dose TNF? induced expression of CXCR6 on the surface of PMN. Furthermore, we could show an increased migration of PMN induced by the axis CXCL16 and CXCR6. In summary, our data provide evidence that CXCR6 is not constitutively expressed on PMN, but is up-regulated under inflammatory conditions and mediates migration of CXCR6-positive PMN.
Gaida, M M; Gunther, F; Wagner, C; Friess, H; Giese, N A; Schmidt, J; Hansch, G M; Wente, M N
A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma
Purpose: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. Methods and Materials: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. Results: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). Conclusions: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs.
Brown, Michael W. [Radiation Oncology Branch, CCR, National Institutes of Health, Bethesda, MD (United States); Ning, Holly [Radiation Oncology Branch, CCR, National Institutes of Health, Bethesda, MD (United States); Arora, Barbara [Radiation Oncology Branch, CCR, National Institutes of Health, Bethesda, MD (United States); Albert, Paul S. [Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Institutes of Health, Bethesda, MD (United States); Poggi, Matthew [Radiation Oncology, National Naval Medical Center, Bethesda, MD (United States); Camphausen, Kevin [Radiation Oncology Branch, CCR, National Institutes of Health, Bethesda, MD (United States); Citrin, Deborah [Radiation Oncology Branch, CCR, National Institutes of Health, Bethesda, MD (United States)]. E-mail: firstname.lastname@example.com
Ultrasonically guided percutaneous implantation of iodine-125 seeds in pancreatic carcinoma
Cancer of the pancreas is most often not diagnosed before it has reached unresectable stages. The development of effective palliative treatment for these patients and for those with recurrence after resection is clearly needed. The present study reports the results of ultrasonically guided percutaneous implantation of {sup 125}I seeds in 19 patients with cancer of the pancreas. Twelve patients had further adjuvant external radiation. Despite satisfactory seed placement and delivery of the planned radiation dose in most cases, clinical improvement was lacking or only slight and short-lived. No difference in survival or palliation was observed between patients treated with seeds alone compared with patients treated with seeds and external radiation. Survival after seed implantation was short (median 140 days, range 7-401 days). Ultrasonically guided percutaneous implantation of {sup 125}I seeds cannot be recommended in the treatment of unresectable carcinoma of the pancreas.
Joyce, F.; Burcharth, F.; Holm, H.H.; Stroyer, I. (Univ. of Copenhagen (Denmark))
Laparoscopy with laparoscopic ultrasonography in the TNM staging of pancreatic carcinoma.
A prospective study was performed comparing laparoscopy with laparoscopic ultrasonography (LapUS), transabdominal ultrasonography (USS), computed tomography (CT), and selective visceral angiography with portal phase venography (SVA) for the assessment of resectability in 50 patients with pancreatic or periampullary cancer. The results were stratified by TNM stages. Tumor unresectability was demonstrated in 36 patients (72%). The sensitivity of LapUS for demonstrating the index lesion was 96%. Laparoscopic ultrasonography failed to predict factors precluding resection by T stage in six patients, and there were no significant differences in the ability of any modality to predict local resectability (predictive value 58-73%). Laparoscopic ultrasonography did not overestimate T stage and was significantly more specific for assessing unresectability compared with USS (100% vs. 64%, p<0.05) and CT (100% vs. 47%, p<0.005). No imaging investigation was able to assess the N stage accurately. Metastases were confirmed in 16 patients (32%), with LapUS proving significantly more sensitive than USS (94% vs. 29%, p<0.001) and CT (94% vs. 33%, p<0.005). The addition of LapUS to the laparoscopic examination did not change the M stage in any patient, as all metastases were superficially located. Laparoscopy with LapUS was the most reliable method for assessing overall tumour resectability and was significantly more predictive than CT (97% vs. 79%, p<0.005). These results confirm that laparoscopy is indispensable for detecting occult intraabdominal metastases. LapUS reliably predicts tumor unresectability, offsetting the tendency of USS and CT to overestimate T stage. Methods of accurate N staging remain elusive, and the use of routine SVA is not justified. PMID:10449813
John, T G; Wright, A; Allan, P L; Redhead, D N; Paterson-Brown, S; Carter, D C; Garden, O J
The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer.
Heparan sulfate proteoglycans (HSPGs) play diverse roles in cell recognition, growth, and adhesion. In vitro studies suggest that cell-surface HSPGs act as coreceptors for heparin-binding mitogenic growth factors. Here we show that the glycosylphosphatidylinositol- (GPI-) anchored HSPG glypican-1 is strongly expressed in human pancreatic cancer, both by the cancer cells and the adjacent fibroblasts, whereas expression of glypican-1 is low in the normal pancreas and in chronic pancreatitis. Treatment of two pancreatic cancer cell lines, which express glypican-1, with the enzyme phosphoinositide-specific phospholipase-C (PI-PLC) abrogated their mitogenic responses to two heparin-binding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor 2 (FGF2) and heparin-binding EGF-like growth factor (HB-EGF). PI-PLC did not alter the response to the non-heparin-binding growth factors EGF and IGF-1. Stable expression of a form of glypican-1 engineered to possess a transmembrane domain instead of a GPI anchor conferred resistance to the inhibitory effects of PI-PLC on growth factor responsiveness. Furthermore, transfection of a glypican-1 antisense construct attenuated glypican-1 protein levels and the mitogenic response to FGF2 and HB-EGF. We propose that glypican-1 plays an essential role in the responses of pancreatic cancer cells to certain mitogenic stimuli, that it is relatively unique in relation to other HSPGs, and that its expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder.
Kleeff, J; Ishiwata, T; Kumbasar, A; Friess, H; Buchler, M W; Lander, A D; Korc, M
EGFR inhibitor gefitinib prevents progression of pancreatic lesions to carcinoma in a conditional LSL-KrasG12D/+ transgenic mice model
Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy with a dismal prognosis. Developing novel strategies to prevent/delay pancreatic cancer is currently of intense interest. The chemopreventive efficacy of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, was evaluated on the progression of pancreatic intraepithelial neoplasms (PanINs) to PDAC in conditional LSL-KrasG12D/+ transgenic mice. LSL-KrasG12D/+ and p48Cre/+ mice were bred and off-spring of activated KrasG12D/+ were generated. Six-week old male KrasG12D/+ (20/group) and C57BL/6 wild-type (12/group) mice were fed (AIN-76A) diets containing 0, 100, and 200 ppm gefitinib for 35 weeks. At termination, pancreases were evaluated histopathologically for PanINs and PDAC, and various biomarkers were measured by IHC, immunofluorescence, immunoblotting and/or RT-PCR. Dietary gefitinib at 100 and 200 ppm significantly suppressed PDAC incidence by 77 and 100%, respectively, (p<0.0001) when compared to control diet. Importantly, significant inhibition of carcinoma and a dose-dependent suppression of PanINs (PanIN1 37 � 62%,p<0.002, PanIN2 38�41,p<0.001, and PanIN3 7�34%, p<0.0141) was observed in mice treated with gefitinib. Furthermore, 100 and 200 ppm gefitinib treated mice exhibited 67.6�77.3% of the pancreas to be free from ductal lesions. Also, gefitinib reduced EGFR, PCNA, Cyclin D1, C2GNT, RhoA, ?-catenin, p38, pERK, caveolin-1, and mucin, and increased cyclin B1 in the pancreatic lesions/PDAC. In summary, these results demonstrate that gefitinib can prevent pancreatic cancer precursor lesions progression to PDAC in a preclinical model. The present study highlights the promise of chemoprevention and the potential usefulness of EGFR inhibitors in high-risk individuals for pancreatic cancer.
Mohammed, Altaf; Janakiram, Naveena B; Li, Qian; Madka, Venkateshwar; Ely, Misty; Lightfoot, Stan; Crawford, Howard; Steele, Vernon E.; Rao, Chinthalapally V.
[The biological behavior of exocrine pancreatic carcinoma from a pathological-anatomical viewpoint. A contribution to the problems of surgical therapy].
The general biologic behaviour of exocrine pancreatic cancer was examined retrospectively in a total of 840 autopsies (382 males, aged 31-86 [average 66.5] and 458 females, aged 2-90 [average 72]). 95 % of autopsies showed definable tumours (caput 64%, corpus 17%, cauda 14%), in 5% the gland was diffusely permeated by cancer tissue. 19.5% had no metastases, whereas in 80.5% carcinomatosis was diagnosed. In 7% only locoregional metastases of the lymph nodes could be found. Tumour sizes were observed in the range of 0.3 to 14 cm. All carcinomas below the size of 1 cm were free of metastases. In tumours larger than 2 cm, the formation of metastases increased sharply. In sizes more than 3 cm complications were important for the prognosis. Carcinomatosis proceeds cascade-fashion with high first rate metastatic spread into the liver. 6% of liver metastases were solitary ones, 94% were multiple. In 171 cases malignancy grading was performed. Free of metastases were 50% of the decreased with grade-I-carcinomas, 21% with grade-II-carcinomas and 7% with grade-III-carcinomas. These data comment on the possibilities and limitations of curative cancer resection from a morphological view. PMID:1776373
Reich, O; Justus, J
Restoration of receptor-type protein tyrosine phosphatase eta function inhibits human pancreatic carcinoma cell growth in vitro and in vivo.
DEP-1/HPTPeta, a receptor-type protein tyrosine phosphatase, is a candidate tumor suppressor gene because its expression was blocked in rat and human thyroid transformed cells, and its restoration reverted their neoplastic phenotype. In addition, loss of DEP-1/HPTPeta heterozygosity has been described in mammary, lung and colon primary tumors. We now show that DEP-1/HPTPeta is drastically reduced in several cell lines originating from human epithelial pancreatic carcinomas compared with normal pancreatic tissue. We also show that the infection of AsPC1 and PSN1 cells with a recombinant adenovirus carrying r-PTPeta cDNA (the rat homolog of DEP-1/HPTPeta) inhibits their proliferation. Flow cytometric analysis of the infected cells demonstrated that restoration of r-PTPeta activity disrupts their cell cycle and leads to apoptosis. Finally, the growth of PSN1 xenograft tumors was blocked by the intratumoral injection of a recombinant adeno-associated virus carrying r-PTPeta. The data suggest that restoration of DEP-1/HPTPeta expression could be a useful tool for the gene therapy of human pancreatic cancers. PMID:15231692
Trapasso, Francesco; Yendamuri, Sai; Dumon, Kristoffel R; Iuliano, Rodolfo; Cesari, Rossano; Feig, Byron; Seto, Robin; Infante, Luisa; Ishii, Hideshi; Vecchione, Andrea; During, Matthew J; Croce, Carlo M; Fusco, Alfredo
Neuroendocrine carcinoma arising in a hepatitis C virus-infected liver: mechanism of the tumor development may be similar to that of development of pancreatic neuroendocrine cells.
We experienced a case of neuroendocrine carcinoma (NC). The tumor developed in the cirrhotic liver of a 62-year-old Japanese man who had been infected with hepatitis C virus. The tumor cells showed high N/C ratio, formed many rosettes, and expressed CD56, synaptophysin, HepPar1 and pancreatic and duodenal homeobox 1. MIB1 expression was 65%. Because both liver and pancreas are derived from a common endodermal layer during fetal development, we speculated that the tumor may have formed via the interaction of neurogenin 3, insulinoma-associated 1 gene and NeuroD/beta2, which are involved in the stage at which some pancreatic cells commit to becoming endocrine cells. Molecular analysis revealed that the NC had higher relative expression levels of mRNA of the three molecules than did the nontumorous liver. The results indicate that the NC in this patient may have formed via the same mechanism that acts in the development of pancreatic neuroendocrine cells. PMID:24629176
Masunaga, Atsuko; Inoue, Kazuaki; Mizukami, Hiroki; Hayashi, Takaki; Mitsuya, Toshiyuki
Growth Factor Mediated Signaling in Pancreatic Pathogenesis
Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.
Nandy, Debashis; Mukhopadhyay, Debabrata
Significance of K- ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer
:�� The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients\\u000a with suspected pancreatic diseases were examined to investigate the value of K-ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), and cytology of pancreatic\\u000a juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without
Noriaki Futakawa; Wataru Kimura; Seiichi Yamagata; Bin Zhao; Han Ilsoo; Tomomi Inoue; Naohiro Sata; Yoneei Kawaguchi; Yoshiro Kubota; Tetsuichiro Muto
Elderly patients with pancreatic cancer.
Pancreatic cancer marked significant increase of incidence during the last decades in the elderly population. Despite the certain increase of incidence there are no international guidelines for elderly patients who are suffering from pancreatic cancer. During the ASCO Annual Meeting 2014, two abstracts focusing on elderly patients suffering from different histological types of pancreatic cancer were presented. The first retrospective study (Abstract #4119) showed the benefit of the systemic treatment on overall survival for elderly patients with stage IV pancreatic adenocarcinoma. The second retrospective study (Abstract #4112) demonstrates the positive effect of somatostatin analogue (octreotide-LAR) treatment on overall survival for elderly patients with neuroendocrine pancreatic carcinoma. PMID:25076333
Kougioumtzopoulou, Andromachi S; Syrigos, Kostas N; Saif, Muhammad Wasif
Anterior approach to the superior mesenteric artery by using nerve plexus hanging maneuver for borderline resectable pancreatic head carcinoma.
To achieve R0 resection for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head, complete resection of the retropancreatic nerve plexus around the superior mesenteric artery (SMA) is thought to be required. Twenty-five patients with borderline resectable right-sided PDAC were divided into two groups after neoadjuvant chemoradiotherapy: those with portal vein (PV) invasion alone (n?=?12), and those with invasion of both PV and SMA (n?=?13). A tape for guidance was passed in a space ventral to the SMA and behind the pancreatic parenchyma, followed by resection of the pancreatic parenchyma with the splenic vein. Another tape was passed behind the nerve plexus lateral to the hepatic artery and the SMA ventral to the inferior vena cava and the nerve plexus was dissected, resulting in complete resection of the nerve plexus around the SMA. Pathological findings revealed that the rates of R0, R01 (a margin less than 1�mm) and R1 were 58.3�%, 41.7�% and 0�% in PV group, and 53.8�%, 30.8�% and 15.4�% in PV/A group, respectively. The median survival time was 23.3 and 22.8�months in PV and PV/A groups, respectively. The plexus hanging maneuver for PDAC of the pancreatic head achieved complete resection of the retropancreatic nerve plexus around the SMA, helping to secure a negative surgical margin. PMID:24664421
Mizuno, Shugo; Isaji, Shuji; Tanemura, Akihiro; Kishiwada, Masashi; Murata, Yasuhiro; Azumi, Yoshinori; Kuriyama, Naohisa; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami
Depression and Pancreatic Cancer: A Poorly Understood Link
Summary Although pancreatic carcinoma and depression have been linked for many years, the prevalence and relationship of these two entities are still poorly understood. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. If the definition of depression is
Nektaria Makrilia; Bonnie Indeck; Kostas Syrigos; Muhammad Wasif Saif
Adenosquamous cell lung cancer successfully treated with gefitinib: A case report
Although adenosquamous cell lung cancer (ASCLC) is included in the non-small-cell lung cancers (NSCLCs), the number of currently available studies on the response of this type of cancer to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is limited. This is the case report of a 66-year-old female who was referred to the Mito Medical Center (Mito, Japan) with hemoptysis and the chest computed tomography (CT) scan revealed a large cavitary mass in the lower lobe of the left lung. The patient underwent surgical resection of the lesion and the final pathological diagnosis was ASCLC staged as pT2bN2M0. Notably, an EGFR exon 19 deletion was identified in the adenocarcinomatous as well as the squamous cell carcinomatous components of the tumor. Despite adjuvant chemotherapy, the patient developed small cavitary metastases in the lungs bilaterally. Therefore, treatment with gefitinib was initiated. The chest CT scan revealed substantial regression of the metastatic cavitary tumors in both lungs, with thinning of the walls. The patient remains alive and recurrence-free 19 months following the initiation of gefitinib therapy. This case demonstrated an optimal clinical response to gefitinib treatment for EGFR mutation-positive ASCLC, suggesting that gefitinib is a therapeutic option for such a subset of patients with ASCLC.
Differential Expression of Human Spasmolytic Polypeptide (Trefoil Factor Family2) in Pancreatic Carcinomas, Ampullary Carcinomas, and Mucin-Producing Tumors of the Pancreas
Human spasmolytic polypeptide (hSP) is a member of the trefoil peptide group, thought to be involved in mucin production and cell growth. It has been reported that hSP protein is expressed in digestive cancers but not in normal pancreas. The expression of hSP in pancreatic neoplasms has not been investigated in detail. The immunohistochemical expression of hSP protein was investigated
Gakuji Ohshio; Hirofumi Suwa; Yoshiya Kawaguchi; Masayuki Imamura; Yoshio Yamaoka; Hirohiko Yamabe; Masao Matsumoto; Hideyuki Yoshioka; Yosuke Hashimoto; Hiroshi Takeda
Epithelial markers in pancreatic carcinoma: immunoperoxidase localisation of DD9, CEA, EMA and CAM 5.2
Paraffin wax embedded, formalin fixed sections of 22 adenocarcinomas of the exocrine pancreas were stained with four mouse monoclonal antibodies: DD9-E7, an antibody raised against a human pancreatic tumour xenograft; carcino-embryonic antigen (CEA); epithelial membrane antigen (EMA); and cytokeratin (CAM 5.2). An indirect immunoperoxidase technique without enzyme pre-digestion and an affinity-purified sheep anti-mouse peroxidase conjugate were used. All of the
E Heyderman; S E Larkin; P J ODonnell; A M Haines; P J Warren; A G Grant
Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial
Purpose Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results 111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%�52% tumor diameter shrinkage). Conclusion 90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer.
Gulec, Seza A.; Cohen, Steven J.; Pennington, Kenneth L.; Zuckier, Lionel S.; Hauke, Ralph J.; Horne, Heather; Wegener, William A.; Teoh, Nick; Gold, David V.; Sharkey, Robert M.; Goldenberg, David M.
Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model
Survivin is overexpressed by 70�80% of pancreatic cancers, and is associated with resistance to chemotherapy and a poor prognosis. Gemcitabine has been a standard treatment for patients with advanced pancreatic cancer for a decade. Recent reports have demonstrated that gemcitabine treatment attenuates the tumor-suppressive environment by eliminating CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs). We hypothesize that a cancer vaccine targeting survivin can achieve enhanced efficacy when combined with gemcitabine. In this study, we tested this hypothesis using modified vaccinia Ankara (MVA) expressing full-length murine survivin. The poorly immunogenic mouse pancreas adenocarcinoma cell line, Pan02, which expresses murine survivin and is syngeneic to C57BL/6, was used for this study. Immunization with MVA-survivin resulted in a modest therapeutic antitumor effect on established Pan02 tumors. When administered with gemcitabine, MVA-survivin immunization resulted in significant tumor regression and prolonged survival. The enhanced vaccine efficacy was associated with decreased CD11b+/Gr-1+ MDSCs. To analyze the survivin-specific immune response to MVA-survivin immunization, we utilized a peptide library of 15mers with 11 residues overlapping from full-length murine survivin. Splenocytes from mice immunized with MVA-survivin produced intracellular ?-interferon in response to in vitro stimulation with the overlapping peptide library. Increased survivin-specific CD8+ T cells that specifically recognized the Pan02 tumor line were seen in mice treated with MVA-survivin and gemcitabine. These data suggest that vaccination with MVA-survivin in combination with gemcitabine represents an attractive strategy to overcome tumor-induced peripheral immune tolerance, and this effect has potential for clinical benefit in pancreatic cancer.
Ishizaki, Hidenobu; Manuel, Edwin R.; Song, Guang-Yun; Srivastava, Tumul; Sun, Sabrina; Diamond, Don J.; Ellenhorn, Joshua D. I.
... Information Animated Pancreas Patient About the Pancreas Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Children/Pediatric Other Pancreas Ailments Patient/Family Information Clinical Trials Financial Assistance Research Research ...
Hedgehog-EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells
Inhibition of Hedgehog (HH)/GLI signalling in cancer is a promising therapeutic approach. Interactions between HH/GLI and other oncogenic pathways affect the strength and tumourigenicity of HH/GLI. Cooperation of HH/GLI with epidermal growth factor receptor (EGFR) signalling promotes transformation and cancer cell proliferation in vitro. However, the in vivo relevance of HH-EGFR signal integration and the critical downstream mediators are largely undefined. In this report we show that genetic and pharmacologic inhibition of EGFR signalling reduces tumour growth in mouse models of HH/GLI driven basal cell carcinoma (BCC). We describe HH-EGFR cooperation response genes including SOX2, SOX9, JUN, CXCR4 and FGF19 that are synergistically activated by HH-EGFR signal integration and required for in vivo growth of BCC cells and tumour-initiating pancreatic cancer cells. The data validate EGFR signalling as drug target in HH/GLI driven cancers and shed light on the molecular processes controlled by HH-EGFR signal cooperation, providing new therapeutic strategies based on combined targeting of HH-EGFR signalling and selected downstream target genes.
Eberl, Markus; Klingler, Stefan; Mangelberger, Doris; Loipetzberger, Andrea; Damhofer, Helene; Zoidl, Kerstin; Schnidar, Harald; Hache, Hendrik; Bauer, Hans-Christian; Solca, Flavio; Hauser-Kronberger, Cornelia; Ermilov, Alexandre N; Verhaegen, Monique E; Bichakjian, Christopher K; Dlugosz, Andrzej A; Nietfeld, Wilfried; Sibilia, Maria; Lehrach, Hans; Wierling, Christoph; Aberger, Fritz
Neuroendocrine pancreatic carcinoma after initial diagnosis of acute postpartal coeliac disease in a 37-year old woman - fatal coincidence or result of a neglected disease?
An acute presentation after pregnancy of coeliac disease (CD) in the puerperium is a rare condition which has been described mostly in primigravidae in patients highly suspicious of latent CD. We report the case of a 37-year-old woman who was referred to our Hospital because of refractory watery diarrhea and malnutrition syndrome. Endoscopy of the upper gastrointestinal tract revealed the classic visual features of CD and in addition, some duodenal ulcers negative for Helicobacter pylori, which seems to be another clinical feature in patients with CD. The diagnosis of acute onset of fulminant postpartal CD (Marsh score stage 3c) was confirmed histologically. Remarkably, simultaneous well-differentiated neuroendocrine non-functioning pancreatic neuroendocrine carcinoma (PNET) was diagnosed on radiological abdominal imaging which was performed since serum gastrin was remarkably high, treated by distal pancreatectomy and splenectomy. This report is, to our knowledge, the first description of the two entities, CD and PNET occurring together. Since results of antral histological studies showed diffuse hyperplasia of G-cells, probably in response to hypergastrinaemia, enterochromaffin cell carcinogenesis might have served as a possible link between both diseases. PMID:24778059
Gundling, Felix; Nerlich, Andreas; Heitland, Wolf; Schepp, Wolfgang
Identification of Hepatocarcinoma-Intestine-Pancreas\\/Pancreatitis-associated Protein I as a Biomarker for Pancreatic Ductal Adenocarcinoma by Protein Biochip Technology1
New biomarkers of pancreatic adenocarcinoma are needed to improve the early detection of this deadly disease. We performed surface enhanced laser desorption ionization (SELDI) mass spectrometry using ProteinChip technology (Ciphergen Biosystems, Fremont, CA) to screen for differen- tially expressed proteins in pancreatic juice. Pancreatic juice samples obtained from patients undergoing pancreatectomy for pancreatic adeno- carcinoma were compared with juice samples
Christophe Rosty; Laurence Christa; Scott Kuzdzal; William M. Baldwin; Marianna L. Zahurak; Francoise Carnot; Daniel W. Chan; Marcia Canto; Keith D. Lillemoe; John L. Cameron; Charles J. Yeo; Ralph H. Hruban; Michael Goggins
[Biological aspects of pancreatic cancer].
Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. These molecular alterations, including overexpression of receptor-ligand systems, oncogene activation and loss of tumour suppressor genes, leads to a profound disturbance in cell cycle regulation and continuous growth. The molecular findings are now integrated in a pancreatic tumour progression model, with genetically and morphological defined precursor lesions. However, it remains unclear whether the initial target cells of this cancer develop from ductal or acinar cells. This review will present recent emerging questions on the biology of pancreatic cancer with particular emphasis on the cell origin and tumour microenvironment. PMID:16172578
Tonel, E; Carbone, A; Scirelli, T; Bellone, G; Emanuelli, G
Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy
Background We aimed to study the predictive value of combined 18F-fluoro-deoxy-D-glucose positron emission tomography and computerized tomography (FDG-PET-CT), on outcomes in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT). Methods Thirty-two unresectable LAPC patients received 50.4 Gy (1.8 Gy/fr) of RT and concurrent 5-FU followed by 4 to 6 cycles of gemcitabine consolidation. Response was evaluated by FDG-PET-CT at post-C-CRT 12-week. Patients were stratified into two groups according to the median difference between pre- and post-treatment maximum standard uptake values (SUVmax) as an indicator of response for comparative analysis. Results At a median follow-up of 16.1 months, 16 (50.0%) patients experienced local/regional failures, 6 of which were detected on the first follow-up FDG-PET-CT. There were no marginal or isolated regional failures. Median pre- and post-treatment SUVmax and median difference were 14.5, 3.9, and -63.7%, respectively. Median overall survival (OS), progression-free survival (PFS), and local-regional progression-free survival (LRPFS) were 14.5, 7.3, and 10.3 months, respectively. Median OS, PFS, and LRPFS for those with greater (N = 16) versus lesser (N = 16) SUVmax change were 17.0 versus 9.8 (p = 0.001), 8.4 versus 3.8 (p = 0.005), and 12.3 versus 6.9 months (p = 0.02), respectively. On multivariate analysis, SUVmax difference was predictive of OS, PFS, and LRPFS, independent of existing covariates. Conclusions Significantly higher OS, PFS, and LRPFS in patients with greater SUVmax difference suggest that FDG-PET-CT-based metabolic response assessment is an independent predictor of clinical outcomes in LAPC patients treated with definitive C-CRT.
A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.
Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).
Rigg, A.; Cunningham, D.; Gore, M.; Hill, M.; O'Brien, M.; Nicolson, M.; Chang, J.; Watson, M.; Norman, A.; Hill, A.; Oates, J.; Moore, H.; Ross, P.
FDG-PET/CT-based restaging may alter initial management decisions and clinical outcomes in patients with locally advanced pancreatic carcinoma planned to undergo chemoradiotherapy
Abstract The impact of [18F]fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) restaging on management decisions and outcomes in patients with locally advanced pancreatic carcinoma (LAPC) scheduled for concurrent chemoradiotherapy (CRT) is examined. Seventy-one consecutive patients with conventionally staged LAPC were restaged with PET/CT before CRT, and were categorized into non-metastatic (M0) and metastatic (M1) groups. M0 patients received 50.4?Gy CRT with 5-fluorouracil followed by maintenance gemcitabine, whereas M1 patients received chemotherapy immediately or after palliative radiotherapy. In 19 patients (26.8%), PET/CT restaging showed distant metastases not detected by conventional staging. PET/CT restaging of M0 patients showed additional regional lymph nodes in 3 patients and tumors larger than CT-defined borders in 4. PET/CT therefore altered or revised initial management decisions in 26 (36.6%) patients. At median follow-up times of 11.3, 14.5, and 6.2 months for the entire cohort and the M0 and M1 cohorts, respectively, median overall survival was 16.1, 11.4, and 6.2 months, respectively; median locoregional progression-free survival was 9.9, 7.8, and 3.4 months, respectively; and median progression-free survival was 7.4, 5.1, and 2.5 months, respectively (P?0.05 each). These findings suggest that PET/CT-based restaging may help select patients suitable for CRT, sparing those with metastases from futile radical protocols, and increasing the accuracy of estimated survival.
Parlak, Cem; Yapar, Ali Fuat
A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer
Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.
Ikeda, Masafumi, E-mail: email@example.com [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan)] [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan)] [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)] [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan)] [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan)] [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan)] [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan)] [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan)] [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan)] [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children's Study, Kyoto University Graduate School of Medicine, Kyoto (Japan)] [Kyoto Unit Center, Japan Environment and Children's Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan)] [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)] [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)
OBJECTIVE: The authors examined the prevalence and complications of pancreatitis in severely burned patients. Factors predictive for the development of pancreatitis after burns are considered. SUMMARY BACKGROUND DATA: Pancreatitis has been documented at necropsy after burns; however, it is not clinically recognized as a common complication of burn injury. Recent improvements in survival rates could yield previously unrecognized complications, such as pancreatitis, particularly in those patients who previously would have not survived. The hypothesis is that pancreatitis is a frequent complication after major burn injury and causes significant morbidity for patients with large burns. METHODS: This retrospective review of adult patients with large burns examines postburn pancreatitis using stepwise logistic regression analysis. RESULTS: Forty-nine of 121 (40%) patients developed hyperamylasemia or hyperlipasemia well after the admission period (23 +/- 3 days), and all enzyme abnormalities were temporally associated with emerging infections. Most of these patients (40/49, 82%) had symptoms of pancreatitis. Three patients (6%) had pancreatic pseudocysts or abscesses. Inhalation injury (p = 0.0001), associated trauma (p = 0.0311), and escharotomy (p = 0.0415) were risk factors for pancreatitis. Using Fischer's exact test, patients with pancreatitis had increased mortality and length of stay. Patients with high enzyme elevations and > or = 50% body surface area burned were at severe risk of pancreatic pseudocyst or abscess development (43%; 90% confidence interval of 23-77%). CONCLUSIONS: Pancreatitis is a frequent complication after large burn injuries. Patients at high risk for pancreatitis complications should receive surveillance examinations during their acute hospitalization.
Ryan, C M; Sheridan, R L; Schoenfeld, D A; Warshaw, A L; Tompkins, R G
Sann-Joong-Kuey-Jian-Tang decreases the protein expression of Mcl?1 and TCTP and increases that of TNF-? and Bax in BxPC?3 pancreatic carcinoma cells.
Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicinal prescription, has been used for the treatment of lymphadenopathy and solid tumors, and has shown therapeutic potential in several human malignant tumor cell lines. However, the efficacy and molecular mechanisms of action of SJKJT in human pancreatic cancer have not yet been elucidated. In the present study, we evaluated the cytotoxic effects of SJKJT on BxPC-3 human pancreatic carcinoma cells by MTT assay. The protein expression levels of myeloid cell leukemia 1 protein (Mcl-1), translationally controlled tumor protein (TCTP), tumor necrosis factor-? (TNF??), caspase-8, caspase-3, Bax and Bcl-2 family in the BxPC-3 cells were measured by western blot analysis. The cell cycle was analyzed by flow cytometry. The protein expression of caspase-3 was also detected by immunocytochemistry (ICC). The results revealed that SJKJT inhibited the proliferation of BxPC-3 cells in a time- and dose-dependent manner. The protein expression levels of TNF-?, caspase-8, caspase-3 and Bax increased in the BxPC-3 cells treated with SJKJT; however, the levels of Mcl-1, TCTP and Bcl-xL decreased. The results also demonstrated that SJKJT increased the percentage of BxPC-3 cells in the sub-G1 phase. In addition, ICC staining indicated that the protein expression of caspase-3 was upregulated in the BxPC-3 cells treated with SJKJT. These findings indicate that SJKJT inhibits the proliferation of BxPC-3 cells through the extrinsic and intrinsic pathway, inducing apoptosis in vitro. Our study, using BxPC-3 human pancreatic cancer cells, demonstrates that SJKJT has potential as a chemotherapeutic agent for the treatment of pancreatic cancer. Further sutdies are warranted to fully elucidate its mechanisms of action. PMID:23652631
Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren; Su, Chin-Cheng
Pancreatic carcinogenesis: apoptosis and angiogenesis.
Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future. PMID:15084979
Onizuka, Shinya; Kawakami, Shunsuke; Taniguchi, Ken; Fujioka, Hikaru; Miyashita, Kosei
Prognostic criteria in nonfunctioning pancreatic endocrine tumours
To identify prognostic subgroups among nonfunctioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion
Stefano La Rosa; C. Capella; F. Sessa; C. Riva; B. E. Leone; C. Klersy; G. Rindi; E. Solcia
The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies.
Maitra, Anirban; Hruban, Ralph H.
Acute Pancreatitis and Pregnancy
Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation of the pancreas manifested ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...
In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption.
We previously demonstrated the synergistic therapeutic effect of the cetuximab (anti-epidermal growth factor receptor [EGFR] monoclonal antibody, mAb)-trastuzumab (anti-HER2 mAb) combination (2mAbs therapy) in HER2(low) human pancreatic carcinoma xenografts. Here, we compared the 2mAbs therapy, the erlotinib (EGFR tyrosine kinase inhibitor [TKI])-trastuzumab combination and lapatinib alone (dual HER2/EGFR TKI) and explored their possible mechanisms of action. The effects on tumor growth and animal survival of the three therapies were assessed in nude mice xenografted with the human pancreatic carcinoma cell lines Capan-1 and BxPC-3. After therapy, EGFR and HER2 expression and AKT phosphorylation in tumor cells were analyzed by Western blot analysis. EGFR/HER2 heterodimerization was quantified in BxPC-3 cells by time-resolved FRET. In K-ras-mutated Capan-1 xenografts, the 2mAbs therapy gave significantly higher inhibition of tumor growth than the erlotinib/trastuzumab combination, whereas in BxPC-3 (wild-type K-ras) xenografts, the erlotinib/trastuzumab combination showed similar growth inhibition but fewer tumor-free mice. Lapatinib showed no antitumor effect in both types of xenografts. The efficacy of the 2mAbs therapy was partly Fc-independent because F(ab')(2) fragments of the two mAbs significantly inhibited BxPC-3 growth, although with a time-limited therapeutic effect. The 2mAbs therapy was associated with a reduction of EGFR and HER2 expression and AKT phosphorylation. BxPC-3 cells preincubated with the two mAbs showed 50% less EGFR/HER2 heterodimers than controls. In pancreatic carcinoma xenografts, the 2mAbs therapy is more effective than treatments involving dual EGFR/HER2 TKIs. The mechanism of action may involve decreased AKT phosphorylation and/or disruption of EGFR/HER2 heterodimerization. PMID:22431920
Larbouret, Christel; Gaborit, Nad�ge; Chard�s, Thierry; Coelho, Micka�l; Campigna, Emmanuelle; Bascoul-Mollevi, Caroline; Mach, Jean-Pierre; Azria, David; Robert, Bruno; P�legrin, Andr�
Orbital Cellulitis: A Rare Presentation of Metastatic Bronchial Carcinoma
Objective. We report a rare and unusual case of bronchial carcinoma presenting with symptoms of complications of sinonasal disease. Case Report. A 66-year-old lady was referred with a 1-week history of progressive ocular pain, chemosis, and visual disturbance. Computed tomography of the paranasal sinuses revealed frontal and ethmoidal sinus opacification with orbital involvement consistent with a diagnosis of orbital cellulitis secondary to sinusitis. Surgical exploration revealed that the sinuses and right orbit were filled with soft tissue and subsequent histopathological examination of the biopsies indicating metastases from an adenosquamous bronchial carcinoma. Further imaging revealed a large, asymptomatic, bronchial primary with deposits in the brain and liver. The advanced presentation of the disease limited treatment to best supportive care. Conclusion. Orbital cellulitis and sinonasal malignancies have a similar pattern of clinical presentation, posing a potential diagnostic pitfall. There are only two previously reported cases of metastatic lung carcinoma in the frontal sinus with 15 cases of sinonasal tract involvement reported overall. There are no reported cases of adenosquamous carcinoma in the sinonasal tract.
Kumar, Rohit; Issing, Wolfgang
Opinion statement��External and internal pancreatic fistulas have a different etiology and natural history. Approximately 50% of internal and\\u000a 70% to 90% of external pancreatic fistulas can be expected to heal with nonoperative management. Nonclosure is predicted by\\u000a anatomic factors, which may be defined at endoscopic retrograde cholangiopancreatography or by CT if disconnected pancreatic\\u000a segments are seen. Enteral nutrition beyond the
Miranda Voss; Theodore Pappas
Diagnosing pancreatic cancer using methylation specific PCR analysis of pancreatic juice.
The aim of this study was to determine the utility of detecting methylated ppENK and pi6 in pancreatic juice by methylation specific PCR as a marker of pancreatic adeno-carcinoma. Pancreatic juice samples were collected either intraoperatively, from 92 patients undergoing pancreaticoduodenectomy for benign (n=20) and malignant periampullary disease (n = 72) or endoscopically (by duodenal aspiration after secretin infusion), from 13 patients undergoing investigation for pancreatic disease. Methylated ppENK was detected in the pancreatic juice of 30 (66.7%) of 45 patients with pancreatic ductal adenocarcinoma, in 4 (44.4%) of 9 patients with intraductal papillary-mucinous adenocarcinoma, and in 7 (41.2%) of 17 patients with other periampullary carcinomas, using methylation specific PCR. Methylated pi6 was detected in a lower percentage of these patients (11.1%, 11.1% and 23.5%, respectively). In contrast, methylated ppENK and pi6 were not detected in 20 patients with non-malignant periampullary disease including 12 patients with chronic pancreatitis. Methylated ppENK was detected in 30 of 33 (90.9%) primary pancreatic adenocarcinoma and methylated pi6 was in 6/33 (1 8.2%). Despite the absence of ppENKand pi6 methylation in normal pancreas, methylated ppENK and pi6 was present in the duodenum of 90.5% and 28.6%, respectively of patients without cancer. Further, methylated ppENK and pi6 was seen in 88.9% and 11.1%, respectively of pancreatic juice samples obtained by duodenal aspiration from patients without cancer. We conclude that since ppENK and pi6 are not normally methylated in pancreatic secretions, detection of methylated ppENK and pi6 in pure pancreatic juice obtained by direct cannulation of the pancreatic duct to avoid duodenal secretions may suggest the presence of pancreatic adenocarcinoma PMID:12673124
Fukushima, Noriyoshi; Walter, Kimberly M; Uek, Takashi; Sato, Norihiro; Matsubayashi, Hiroyuki; Cameron, John L; Hruban, Ralph H; Canto, Marcia; Yeo, Charles J; Goggins, Michael
Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer
AIM: To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels. METHODS: In 86 patients with suspected chronic pancreatitis (age: 62?�?12 years; sex: f/m 38/48), pancreatic lesions were examined by conventional endoscopic B-mode, power Doppler ultrasound and contrast-enhanced power mode (Hitachi EUB 525, SonoVue�, 2.4 mL, Bracco) using the following criteria for malignant lesions: no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue� contrast-enhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound (EUS)-guided fine needle aspiration cytology, operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue�, regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue� and detection of arterial and venous vessels. RESULTS: The sensitivity and specificity of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3% in 28 of 30 patients with chronic inflammatory pancreatic disease. CONCLUSION: Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.
Hocke, Michael; Schulze, Ewald; Gottschalk, Peter; Topalidis, Theodor; Dietrich, Christoph F
Pancreatic enzyme therapy for pancreatic exocrine insufficiency
Pancreatic exocrine insufficiency with steatorrhea is a major consequence of pancreatic diseases (eg, chronic pancreatitis,\\u000a cystic fibrosis, severe acute necrotizing pancreatitis, pancreatic cancer), extrapancreatic diseases such as celiac disease\\u000a and Crohn�s disease, and gastrointestinal and pancreatic surgical resection. Recognition of this entity is highly relevant\\u000a to avoid malnutrition-related morbidity and mortality. Therapy for pancreatic exocrine insufficiency is based on the
J. Enrique Dom�nguez-Mu�oz
Melatonin influences pancreatic cancerogenesis.
Pancreatic cancer has fatal prognosis because of the absence of early symptoms, late diagnosis and the resistance to radio- and chemotherapy. Melatonin, an indoleamine discovered in the pineal gland, has also been detected in the gastrointestinal system and its specific receptors have been identified in the pancreas. Some evidence indicates that melatonin could modulate the process of pancreatic oncogenesis: 1) Melatonin, as direct scavenger of radical oxygen and nitrogen species (ROS and RNS) and activator of antioxidant enzymes effectively protects the pancreatic tissue against oxidative stress and inflammatory damage. 2) In pancreatic carcinoma cell line (PANC-1) melatonin used at high doses affects the Bax/Bcl protein balance, and stimulates the expressions of caspase-9 and caspase-3, thus activating the mitochondrial pathway of apoptosis. On the contrary, low concentrations of melatonin turn on the production of anti-apoptotic heat shock proteins: HSP27, HSP70, and HSP90, which prevents the activation of caspase-3. 3) Melatonin reduces angiogenesis and decreases proliferation of endothelial cells through inhibition of vascular endothelial factor (VEGF). 4) Melatonin strengthens the immune defense of the organism via activation of peripheral effector T cells and suppression of T regulatory cells. 5) In animal studies melatonin has been found to increase the efficacy of oncostatic drugs, to reduce the side effects of chemotherapy and to decrease morbidity. These observations suggest that melatonin at high doses could be potentially taken into consideration as the supportive treatment in the therapy of pancreatic cancer, although the effect of melatonin on apoptosis requires further study. PMID:24258787
Jaworek, Jolanta; Leja-Szpak, Anna
Pancreatic pseudocysts are complications of acute or chronic pancreatitis. Initial diagnosis is accomplished most often by cross-sectional imaging. Endoscopic ultrasound with fine needle aspiration has become the preferred test to help distinguish pseudocyst from other cystic lesions of the pancreas. Most pseudocysts resolve spontaneously with supportive care. The size of the pseudocyst and the length of time the cyst has
Samir Habashi; Peter V Draganov
Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL-KrasG12D/+ mice.
Pancreatic cancer is the one of most common causes of cancer deaths and has the worst prognosis. Clinical observational studies suggest that statins may reduce the risk of pancreatic cancer. The chemopreventive efficacy of the statin atorvastatin (Lipitor(�)) and the role of the phosphatidyl-inositol 3-kinase (PI3/AKT) signaling pathway were evaluated for the progression of pancreatic intraepithelial neoplasms (PanINs) to pancreatic ductal adenocarcinoma (PDAC) in conditional p48(Cre/+) -LSL-Kras(G12D/+) transgenic mice. Six-week-old male p48(Cre/+) -LSL-Kras(G12D/+) (20/group) mice were fed AIN-76A diets containing 0, 200 and 400 ppm atorvastatin for 35 weeks. At termination, pancreata were evaluated histopathologically for PanINs and PDAC, and for various PI3/AKT signaling markers, and inflammatory cytokines, by immunohistochemistry/immunohistoflourscence, ELISA, Western blotting and/or reverse transcription-PCR methods. Control diet-fed mice showed 85% incidence of PDAC; whereas, mice fed with atorvastatin showed PDAC incidence of 65 and 35%, respectively (p < 0.0001). Similarly, significant suppression of PanIN-3 (22.6%) was observed in mice fed 400 ppm atorvastatin. Importantly, pancreata from atorvastatin-treated mice were ?68% free from ductal lesions. Furthermore, pancreas of mice administered with atorvastatin had significantly reduced expressions levels of PCNA, p2X7, p-ERK, RhoA, cyclin D1, survivin, Akt, pAKT, ?-catenin, cyclin E, cdK2 and caveolin-1. Also, atorvastatin-treated mice had shown dose-dependent suppression of inflammatory cytokines and a significant increase in tunnel-positive cells, p21 and PARP expression levels in pancreas. Atorvastatin significantly delays the progression of PanIN-1 and -2 lesions to PanIN-3 and PDAC by modulating PI3/AKT signal molecules in a preclinical model, suggesting potential clinical benefits of statins for high-risk pancreatic cancer patients. PMID:22287227
Mohammed, Altaf; Qian, Li; Janakiram, Naveena B; Lightfoot, Stan; Steele, Vernon E; Rao, Chinthalapally V
Local Staging of Pancreatic Cancer: Criteria for Unresectability of Major Vessels as Revealed by Pancreatic-Phase, Thin-Section Helical CT
OBJECTIVE. This study was conducted to determine the criteria for unresectability of major peripancreatic vessels in patients with pancreatic carcinoma as revealed by optimally enhanced. pancreatic-phase thin-section helical CT. SUBJECTS AND METHODS. Twenty-five patients with pancreatic adenocarcinoma who underwent local dissection during curative or palliative surgery also underwent preoperative pancreatic-phase thin-section helical CT (40- to 70-sec delay. 2.5- to 3-mm
David S. K. Lu; Howard A. Reber; Robert M. KraSny; Barbara M. Kadell; Jim Sayre
Prognostic significance of angiogenesis in human pancreatic cancer
To evaluate whether angiogenic factors are of clinical relevance to actual human pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD-ECGF, VEGF protein expression in 40 pancreatic cancers using immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30 carcinomas (75.0%) were evaluated to be PD-ECGF-positive and 10
N Ikeda; M Adachi; T Taki; C Huang; H Hashida; A Takabayashi; M Sho; Y Nakajima; H Kanehiro; M Hisanaga; H Nakano; M Miyake
TGF-beta signaling in pancreatic cell differentiation
Introduction: TGF-beta signaling has been implicated in pancreatic cancer due to the prevalence of smad4 mutations. An established model for pancreatic endocrine differentiation is exendin-4 (glucagon-like peptide-1 analog) treatment of AR42J cells (rat pancreatic carcinoma cell line). We studied TGF-beta superfamily signaling and downstream intracellular effectors (smad proteins) implicated in many developmental processes. Here, we found a novel interdependence between
Mark Hembree; Kok-Hooi Yew; Krishna Prasadan; Barry Preuett; Christina Cantu; Christopher McFall; Amanda Crowley; Susan Sharp; Charles Snyder; George Gittes
[Autoimmune pancreatitis mimicking pancreatic tumor].
Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. AIP belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20-30%. Differentiation of AIP from the more common pancreatic cancer can be very challenging. About 20% of autoimmune pancreatitis is diagnosed postoperatively during final histological examination. While each of diagnostic investigations provide some additional information towards definitive diagnosis, the question still remains whether it is possible to prevent unnecessary pancreatic resection. We demonstrate the differential diagnostic opportunities when we present our case as well as discuss the literature data of this condition. In conclusion, we think that in case of a focal pancreatic lesion AIP should always be considered. PMID:24566656
Dede, Krist�f; Salamon, Ferenc; Taller, Andr�s; Bursics, Attila
Early ductal lesions of pancreatic carcinogenesis in animals and humans
Summary��Two cases of human early pancreatic duct adenocarcinoma were presented, and ductal lesions observed histologically were compared\\u000a to those induced in hamsters using a rapid-production model of pancreatic carcinoma. In human cases, direct histologic evidence\\u000a was obtained to suggest that cancerous changes arose from duct epithelial cell hyperplasia, because lesions of hyperplasia\\u000a and carcinoma coexisted in continuity. In hamster serialkilling
Yoichi Konishi; Kazuhiro Mizumoto; Shunji Kitazawa; Toshifumi Tsujiuchi; Masahiro Tsutsumi; Toshiki Kamano
Introduction Chronic pancreatitis affects 3�9 people in 100,000; 70% of cases are alcohol-induced. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of lifestyle interventions in people with chronic pancreatitis? What are the effects of dietary supplements in people with chronic pancreatitis? What are the effects of drug interventions in people with chronic pancreatitis? What are the effects of nerve blocks for pain relief in people with chronic pancreatitis? What are the effects of different invasive treatments for specific complications of chronic pancreatitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: avoiding alcohol consumption, biliary decompression, calcium supplements, ductal decompression (endoscopic or surgical), low-fat diet, nerve blocks, opioid analgesics, pancreatic enzyme supplements, pseudocyst decompression (endoscopic or surgical), resection using distal pancreatectomy, resection using pancreaticoduodenectomy (Kausch�Whipple or pylorus-preserving), and vitamin/antioxidant supplements.
Introduction Chronic pancreatitis affects 3�9 people in 100,000; 70% of cases are alcohol-induced. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of lifestyle interventions in people with chronic pancreatitis? What are the effects of dietary supplements in people with chronic pancreatitis? What are the effects of drug interventions in people with chronic pancreatitis? What are the effects of nerve blocks for pain relief in people with chronic pancreatitis? What are the effects of different invasive treatments for specific complications of chronic pancreatitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: avoiding alcohol consumption, biliary decompression, calcium supplements, ductal decompression (endoscopic or surgical), low-fat diet, nerve blocks, opioid analgesics, pancreatic enzyme supplements, pseudocyst decompression (endoscopic or surgical), resection using distal pancreatectomy, resection using pancreaticoduodenectomy (Kausch�Whipple or pylorus-preserving), and vitamin/antioxidant supplements.
Sarcoidosis affects every organ in the body; the most frequently involved structures are the lung, lymph nodes, liver, spleen, eyes, joints and heart. Gastrointestinal system affliction is uncommon. The pancreas is rarely affected by sarcoidosis. A review of the literature revealed only 13 patients with biopsy proven granulomas in pancreas or peripancreatic nodes. In a review of all autopsies performed between 1950 and 1993 at Los Angeles County + University of Southern California School of Medicine, Los Angeles, USA, the authors found one patient with pancreatic and 5 with peripancreatic lymph node granuloma. The authors also describe three previously unreported cases of pancreatic sarcoidosis. From the discussion, a clinically useful and pragmatic profile of pancreatic sarcoidosis emerges. Two thirds of the patients with pancreatic sarcoidosis have abdominal pain, and three quarters of them have bilateral hilar adenopathy. The occurrence of abdominal pain in a woman with bilateral hilar adenopathy with or without pulmonary infiltration should lead one to think of pancreatic sarcoidosis. The diagnosis should be established by a tissue biopsy because the laboratory and radiographic techniques do not differentiate pancreatic sarcoidosis from other inflammatory and malignant disorders of the pancreas. The prognosis of pancreatic sarcoidosis is good. PMID:8865406
Garcia, C; Kumar, V; Sharma, O P
Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50?% of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease. PMID:24193862
Beyer, G; Menzel, J; Kr�ger, P-C; Ribback, S; Lerch, M M; Mayerle, J
Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/? pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year�s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP.
DiMagno, Matthew J.; DiMagno, Eugene P.
Pancreatic cystadenocarcinoma associated with strongyloides.
A 60-year-old woman presented with a mass in the left upper abdominal quadrant. Noninvasive studies showed a cystic structure arising from the pancreas. Pathologic studies of the tumor revealed pancreatic cystadenocarcinoma; the fluid contained Strongyloides larvae. There was no evidence of disseminated Strongyloides or immunosuppression. Results of stool examinations were also negative for Strongyloides. Were these larvae the etiologic agent for the carcinoma? Other parasitic infestations have been associated with carcinoma. This is the first reported association between Strongyloides and cystadenocarcinoma. PMID:6741978
Setia, U; Bhatia, G
Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2
Due to intrinsic aggressiveness and lack of effective therapies, prognosis of pancreatic cancer remains dismal. Because the only molecular targeted drug approved for pancreatic ductal adenocarcinoma is a kinase inhibitor specific to the epidermal growth factor receptor (EGFR), and this receptor collaborates with another kinase, called HER2 (human EGF-receptor 2), we assumed that agents targeting EGFR and/or HER2 would effectively retard pancreatic ductal adenocarcinoma. Accordingly, two immunological strategies were tested in animal models: (i) two antibodies able to engage distinct epitopes of either EGFR or HER2 were separately combined, and (ii) pairs of one antibody to EGFR and another to HER2. Unlike the respective single monoclonal antibodies, which induced weak effects, both types of antibody combinations synergized in animals in terms of tumor inhibition. Immunological cooperation may not depend on receptor density, antigenic sites, or the presence of a mutant RAS protein. Nevertheless, both types of antibody combinations enhanced receptor degradation. Future efforts will examine the feasibility of each strategy and the potential of combining them to achieve sustained tumor inhibition.
Maron, Ruth; Schechter, Bilha; Mancini, Maicol; Mahlknecht, Georg; Yarden, Yosef; Sela, Michael
Pancreatic head carcinoma and vascular endothelial growth factor (VEGF-A) concentration in portal blood: its association with cancer grade, tumor size and probably poor prognosis
Introduction Vascular endothelial growth factor (VEGF) is overexpressed in pancreatic cancer. Although VEGF has been shown to be a probable marker for poor prognosis, the VEGF concentration in portal blood has not yet been clinically reported in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to measure VEGF-A portal blood concentration in patients with PDAC and to evaluate its performance as a prognostic marker. Material and methods Thirty-six consecutive patients out of 57 operated on for pancreatic head lesion with pathologically verified diagnosis of PDAC were enrolled in this study. We evaluated the VEGF concentration in portal blood samples obtained intraoperatively and associated their values with tumor size, stage, grade and survival. Results The portal VEGF-A concentration was associated with tumor grade (G1: 80.52 �43.05 vs. G2: 185.39 �134.98, p = 0.006, G2: 185.39 �134.98 vs. G3: 356.46 �229.12, p = 0.08), and there was a positive correlation with tumor size (r = 0.42, p < 0.05). In the multivariate regression analysis high levels of VEGF-A were not correlated with poor survival (HR = 5.22, 95% CI = �0.6457 to 3.9513, p = 0.19). Conclusions The portal VEGF-A concentration is associated with tumor grade and size. The correlation of portal VEGF-A with poor survival is not clear and needs further investigation.
Durczynski, Adam; Kumor, Anna; Strzelczyk, Janusz
Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer
Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma
Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer
Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma
Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis
Hedgehog signalling-an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer-may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh
Sarah P. Thayer; Marina Pasca di Magliano; Patrick W. Heiser; Corinne M. Nielsen; Drucilla J. Roberts; Gregory Y. Lauwers; Yan Ping Qi; Stephan Gysin; Carlos Fern�ndez-del Castillo; Vijay Yajnik; Bozena Antoniu; Martin McMahon; Andrew L. Warshaw; Matthias Hebrok
Preoperative Diagnosis of Lymph Node Metastasis in Biliary and Pancreatic Carcinomas: Evaluation of the Combination of Multi-detector CT and Serum CA19-9 Level
Background��It is difficult to diagnose lymph node metastasis in biliary and pancreas carcinomas before surgery.\\u000a \\u000a \\u000a \\u000a Aim��The aim of this study was to assess the utility of the combination of multi-detector computed tomographic (MDCT) findings\\u000a and serum carbohydrate antigen (CA)19-9 level in the diagnosis of lymph node metastasis in biliary and pancreas carcinomas.\\u000a \\u000a \\u000a \\u000a \\u000a Methods��The subjects were 139 patients with biliary and
Atsushi NanashimaIchiro; Ichiro Sakamoto; Tomayoshi Hayashi; Syuuichi Tobinaga; Masato Araki; Masaki Kunizaki; Takashi Nonaka; Hiroaki Takeshita; Shigekazu Hidaka; Terumitsu Sawai; Toru Yasutake; Takeshi Nagayasu
Identification of c-FLIPL and c-FLIPS as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells
BackgroundEvasion of apoptosis is a hallmark of pancreatic cancer. However, the underlying mechanisms are still only partly understood and may involve antiapoptotic proteins such as c-FLIP. Here, the role of c-FLIP in the regulation of death receptor-mediated apoptosis in pancreatic cancer was investigated.MethodsExpression of c-FLIPL and c-FLIPS was analysed in primary pancreatic carcinoma samples, pancreatic carcinoma cell lines and primary
Christian Haag; Dominic Stadel; Shaoxia Zhou; Max G Bachem; Peter M�ller; Klaus-Michael Debatin; Simone Fulda
[Cytodiagnosis of pancreatic juice and gall (author's transl)].
In 260 cytologic examinations of pancreatic juice and gall we were able to make a reliable diagnosis in 75%. 90% of the samples were taken before an ERCP. In the cytogram the cells of the gall passages, of the duodenum, and of the pancreas are easily distinguishable. Degenerative pancreas epithelia appear not only in pancreatitis but also in pancreatic carcinoma. 78% of the cases of pancreatic cancer were cytologically positive. By combining cytological examination with ERCP we can attain a large degree of reliability in the detection of cancer. PMID:703669
Fladerer, H; Kratochvil, P; Brandst�tter, G; Wiedner, F; Justich, E
Isolated pancreatic tuberculosis masquerading as pancreatic cancer
Isolated pancreatic tuberculosis (TB) remains a rarity despite the high incidence of tuberculosis in many of the African and Asian countries. Presentation as discrete pancreatic mass often masquerades as pancreatic neoplasm and diagnosis may require histology. Extra-hepatic portal hypertension due to splenic vein thrombosis complicating pancreatic TB has been reported in the literature. We report here a case of isolated pancreatic TB with pancreatic head mass mimicking neoplasm with extra-hepatic portal hypertension. The possibility of TB should be considered in the list of differential diagnoses of pancreatic mass and an endoscopic, ultrasound-guided biopsy might help to clinch the diagnosis of this potentially curable disease.
Zacharia, George S.; Antony, Rajany; Kolassery, Sandesh; Ramachandran, Thazhath M.
[Jejuno-jejunal intussusception as presentation of a primary lung carcinoma: a case report].
Intestinal metastases from lung cancer are exceptional and even more rare is their manifestation before the primary tumor. The clinical manifestation may require surgical resection because of intestinal perforation, hemorrhage, intestinal obstruction or partial blockage as in the case that we report. Survival in the few cases reported, is low and generally does not exceed 20 weeks, regardless of the treatment performed. We report the case of a jejuno-jejunal intussusception manifested by occlusive syndrome and gastrointestinal bleeding due to the metastasis of an adenosquamous lung carcinoma. PMID:22616498
Pratto, Daniel; Resial, Marcelo; Wulfson, Adolfo; Gennaro, Mar�a; Brarda, Marina; Schmidt, Adri�n
Whole Exome Sequencing of Pancreatic Neoplasms with Acinar Differentiation
Pancreatic carcinomas with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma, and carcinomas with mixed differentiation, are distinct pancreatic neoplasms with poor prognosis. Although recent whole exome sequencing analyses have defined the somatic mutations that characterize the other major neoplasms of the pancreas, the molecular alterations underlying pancreatic carcinomas with acinar differentiation remain largely unknown. In the current study, we sequenced the exomes of 23 surgically resected pancreatic carcinomas with acinar differentiation. These analyses revealed a relatively large number of genetic alterations at both the individual base pair and chromosomal levels. There was an average of 119 somatic mutations per carcinoma. When three outliers were excluded, there was an average of 64 somatic mutations per tumor (range 12�189). The mean fractional allelic loss (FAL) was 0.27 (range 0�0.89) and heterogeneity at the chromosome level was confirmed in selected cases using fluorescent in situ hybridization (FISH). No gene was mutated in >30% of the cancers. Genes altered in other neoplasms of the pancreas were occasionally targeted in carcinomas with acinar differentiation; SMAD4 was mutated in six tumors (26%), TP53 in three (13%), GNAS in two (9%), RNF43 in one (4%) and MEN1 in one tumor (4%). Somatic mutations were identified in genes in which constitutional alterations are associated with familial pancreatic ductal adenocarcinoma, such as ATM, BRCA2, and PALB2 (one tumor each), as well as in genes altered in extra-pancreatic neoplasms, such as JAK1 in four tumors (17%) BRAF in three (13%), RB1 in three (13%), APC in two (9%), PTEN in two (9%), ARID1A in two (9%), MLL3 in two (9%), and BAP1 in one (4%). Perhaps most importantly, we found that more than a third of these carcinomas have potentially targetable genetic alterations including mutations in BRCA2, PALB2, ATM, BAP1, BRAF and JAK1.
Jiao, Yuchen; Yonescu, Raluca; Offerhaus, G Johan A; Klimstra, David S; Maitra, Anirban; Eshleman, James R; Herman, James G; Poh, Weijie; Pelosof, Lorraine; Wolfgang, Christopher L.; Vogelstein, Bert; Kinzler, Kenneth W; Hruban, Ralph H; Papadopoulos, Nickolas; Wood, Laura D
Whole-exome sequencing of pancreatic neoplasms with acinar differentiation.
Pancreatic carcinomas with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma and carcinomas with mixed differentiation, are distinct pancreatic neoplasms with poor prognosis. Although recent whole-exome sequencing analyses have defined the somatic mutations that characterize the other major neoplasms of the pancreas, the molecular alterations underlying pancreatic carcinomas with acinar differentiation remain largely unknown. In the current study, we sequenced the exomes of 23 surgically resected pancreatic carcinomas with acinar differentiation. These analyses revealed a relatively large number of genetic alterations at both the individual base pair and chromosomal levels. There was an average of 119 somatic mutations/carcinoma. When three outliers were excluded, there was an average of 64 somatic mutations/tumour (range 12-189). The mean fractional allelic loss (FAL) was 0.27 (range 0-0.89) and heterogeneity at the chromosome level was confirmed in selected cases using fluorescence in situ hybridization (FISH). No gene was mutated in?>30% of the cancers. Genes altered in other neoplasms of the pancreas were occasionally targeted in carcinomas with acinar differentiation; SMAD4 was mutated in six tumours (26%), TP53 in three (13%), GNAS in two (9%), RNF43 in one (4%) and MEN1 in one (4%). Somatic mutations were identified in genes in which constitutional alterations are associated with familial pancreatic ductal adenocarcinoma, such as ATM, BRCA2 and PALB2 (one tumour each), as well as in genes altered in extra-pancreatic neoplasms, such as JAK1 in four tumours (17%), BRAF in three (13%), RB1 in three (13%), APC in two (9%), PTEN in two (9%), ARID1A in two (9%), MLL3 in two (9%) and BAP1 in one (4%). Perhaps most importantly, we found that more than one-third of these carcinomas have potentially targetable genetic alterations, including mutations in BRCA2, PALB2, ATM, BAP1, BRAF and JAK1. PMID:24293293
Jiao, Yuchen; Yonescu, Raluca; Offerhaus, G Johan A; Klimstra, David S; Maitra, Anirban; Eshleman, James R; Herman, James G; Poh, Weijie; Pelosof, Lorraine; Wolfgang, Christopher L; Vogelstein, Bert; Kinzler, Kenneth W; Hruban, Ralph H; Papadopoulos, Nickolas; Wood, Laura D
Pancreatic pseudocysts are complications of acute or chronic pancreatitis. Initial diagnosis is accomplished most often by cross-sectional imaging. Endoscopic ultrasound with fine needle aspiration has become the preferred test to help distinguish pseudocyst from other cystic lesions of the pancreas. Most pseudocysts resolve spontaneously with supportive care. The size of the pseudocyst and the length of time the cyst has been present are poor predictors for the potential of pseudocyst resolution or complications, but in general, larger cysts are more likely to be symptomatic or cause complications. The main two indications for some type of invasive drainage procedure are persistent patient symptoms or the presence of complications (infection, gastric outlet or biliary obstruction, bleeding). Three different strategies for pancreatic pseudocysts drainage are available: endoscopic (transpapillary or transmural) drainage, percutaneous catheter drainage, or open surgery. To date, no prospective controlled studies have compared directly these approaches. As a result, the management varies based on local expertise, but in general, endoscopic drainage is becoming the preferred approach because it is less invasive than surgery, avoids the need for external drain, and has a high long-term success rate. A tailored therapeutic approach taking into consideration patient preferences and involving multidisciplinary team of therapeutic endoscopist, interventional radiologist and pancreatic surgeon should be considered in all cases.
Habashi, Samir; Draganov, Peter V
Pancreatic Exocrine Tumors More than 95% of pancreatic cancers are classified as exocrine tumors. These tumors start in the exocrine cells of the pancreas. The following table describes the most common pancreatic ...
Is Pancreatic Cancer Hereditary?
... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... It has been estimated that ten percent of pancreatic cancers are hereditary. Many of these occur as part ...
Endocrine, Pancreatic Neuroendocrine Tumors
Pancreatic Neuroendocrine Tumors Some rare forms of pancreatic cancer form from the abnormal growth of hormone-producing cells in the pancreas called islet cells. These tumors are known as pancreatic neuroendocrine tumors ( ...
... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 4 View/Download: Small: 533x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 4 Description: Stage IV pancreatic cancer; drawing ...
... Search Quick Search Image Details Pancreatic Cancer Stage 3 View/Download: Small: 720x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing shows cancer ...
The management of pancreatic cancer is complex and prognosis is poor. The etiopathogenesis of pancreatic cancer has been related to several factors, such as diabetes mellitus, smoking and alcohol use, the presence of pancreatic cystic lesions and distinct genetic syndromes. Among the diagnostic options, endoscopic ultrasound (EUS) continues to be developed, with the use of elastography, contrast agents and EUS-guided aspiration and the application of technical improvements that increase diagnostic efficacy (such as the use of specific stains, new aspiration needles, etc.). New biomarkers are also being sought that would help in differential diagnosis, such as M2PK, adiponectin, and Reg4. Among prognostic factors, the importance of nodal involvement and study of surgical resection margins has been confirmed. The role of individual predisposition in determining response to specific treatments continues to be investigated. Research also continues into the development of EUS-guided injection of therapeutic substances and the role of oncological treatment, with new data on the utility of gemcitabine and of statins as mediators of angiogenic suppression or of high-dose vitamin C with cytotoxic effects. Notable in the field of palliative treatment is the development of new biliary stents that aim to reduce obstruction rates. The development of EUS and EUS-guided fine-needle aspiration has been crucial in cystic pancreatic tumors, especially in distinguishing benign from malignant lesions or those with potential for malignant transformation (presence of mural modules, dilatation of the main pancreatic duct, the presence of masses, CEA levels, etc.). The characteristics of these tumors must be determined to evaluate whether surgery or conservative management is the best therapeutic option. PMID:19434873
Iglesias-Garc�a, Julio
Pancreatic enzyme replacement therapy during pancreatic insufficiency.
Pancreatic stimulation and therefore digestion is a tightly controlled and hormonally mediated process. Any alterations affecting any of the systematic steps for successful digestion and absorption to occur will impair appropriate pancreatic enzymatic secretion, entry into the bowel lumen, functionality once inside the lumen, and thus appropriate mixing with foods and nutrients. Many causes of pancreatic insufficiency may require the initiation of pancreatic enzyme therapy, including but not limited to cystic fibrosis, pancreatic cancer, acute and chronic pancreatitis, and pancreatic surgery. This purpose of this article is to help clarify the conditions that cause pancreatic insufficiency, how to determine if the patient is malabsorbing, and the best use of pancreatic enzyme replacement therapy for treatment in these conditions. The first step in determining if pancreatic enzyme therapy is appropriate is to determine if the patient is malabsorbing specifically due to pancreatic exocrine insufficiency. An overview of the methods used to determine pancreatic insufficiency is provided, as well as appropriate treatment methods. Recent Food and Drug Administration regulations require a more thorough process, including randomized controlled trials to prove the safety and efficacy of pancreatic enzymes, to approve them for use. The studies used to verify efficacy also are examined. Last, dosing guidelines and some unconventional ways to administer pancreatic enzymes, such as during enteral feedings, are reviewed. PMID:24687867
Berry, Amy J
GPC1 Regulated by miR-96-5p, Rather than miR-182-5p, in Inhibition of Pancreatic Carcinoma Cell Proliferation
To determine the relationships between miR-96-5p/-182-5p and GPC1 in pancreatic cancer (PC), we conducted the population and in vitro studies. We followed 38 pancreatic cancer patients, measured and compared the expression of miR-96-5p/-182-5p, GPC1, characteristics and patients� survival time of different miR-96-5p/-182-5p expression levels in PC tissues. In an in vitro study, we investigated the proliferation, cycle and apotosis in cells transfected with mimics/inhibitors of the two miRNAs, and determine their effects on GPC1 by dual-luciferase assay. In the follow-up study, we found that the expressions of miR-96-5p/-182-5p were lower/higher in PC tissues; patients with lower/higher levels of miR-96-5p/-182-5p suffered poorer characteristics and decreased survival time. In the in vitro study, the expressions of miR-96-5p/-182-5p were different in cells. Proliferation of cells transfected with miR-96-5p mimics/inhibitors was lower/higher in Panc-1/BxPC-3; when transfected with miR-182-5p mimics/inhibitors, proliferation of cells were higher/lower in AsPC-1/Panc-1. In a cell cycle study, panc-1 cells transfected with miR-96-5p mimics was arrested at G0/G1; BxPC-3 cells transfected with miR-96-5p inhibitors showed a significantly decrease at G0/G1; AsPC-1 cells transfected with miR-182-5p mimics was arrested at S; Panc-1 cells transfected with miR-182-5p inhibitors showed a decrease at S. MiR-96-5p mimics increased the apoptosis rate in Panc-1 cells, and its inhibitors decreased the apoptosis rate in BxPC-3. Dual luciferase assay revealed that GPC1 was regulated by miR-96-5p, not -182-5p. We found that miR-96-5p/-182-5p as good markers for PC; miR-96-5p, rather than -182-5p, inhibits GPC1 to suppress proliferation of PC cells.
Li, Chunlong; Du, Xuefei; Tai, Sheng; Zhong, Xiangyu; Wang, Zhidong; Hu, Zhanliang; Zhang, Lei; Kang, Pengcheng; Ji, Daolin; Jiang, Xingming; Zhou, Qingxin; Wan, Ming; Jiang, Guixing; Cui, Yunfu
Specific Antigen in Serum of Patients with Colon Carcinoma
The binding of monoclonal antibody specific for colon carcinoma was inhibited by serum from patients with adenocarcinoma of the colon but not by serum from patients with other bowel diseases or from healthy volunteers. Of other malignancies studied, serum from two patients with gastric carcinoma and two patients with pancreatic carcinoma also inhibited the specific binding of monoclonal antibody. The
Hilary Koprowski; Meenhard Herlyn; Zenon Steplewski; Henry F. Sears
Acinar cell carcinoma with fatty change arising from the pancreas
Acinar cell carcinoma of the pancreas is a rare malignant tumour developing from acinar cells, accounting for approximately 1% of pancreatic exocrine tumours. We experienced a case of an acinar cell carcinoma with fatty change. To the best of our knowledge, this is the first case report of an acinar cell carcinoma with fatty change in the clinical literature.
Chung, W-S; Park, M-S; Kim, D W; Kim, K W
New developments in diagnosis and non-surgical treatment of chronic pancreatitis.
Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. PMID:24251715
Inui, Kazuo; Yoshino, Junji; Miyoshi, Hironao; Yamamoto, Satoshi; Kobayashi, Takashi
The expression and phosphorylation of ezrin and merlin in human pancreatic cancer.
Pancreatic carcinoma is the most common pancreatic malignancy and is associated with a very poor prognosis. Therefore, new prognostic factors and new treatment strategies are clearly needed. In this study, we retrospectively studied the levels of phosphorylated ezrin in 19 patients with pancreatic carcinoma by immunohistochemical analysis and determined the correlation between protein expression, clinicopathological characteristics and prognosis in pancreatic adenocarcinoma. We also characterized the phenotype of the overexpression of wild-type and phosphorylated ezrin and merlin in human pancreatic cancer cell lines. A significant correlation between the levels of phosphorylated ezrin�353 and ezrin�567 and the stage of pancreatic cancer was observed. Moreover, Kaplan-Meier analysis revealed that patients with high levels of phosphorylated ezrin had a significantly poorer survival rate (P<0.05). In addition, the overexpression of wild-type merlin or ezrin inhibited cell proliferation, migration and adhesion. However, the overexpression of T567D ezrin, a mutant that mimics permanent phosphorylation, promoted the proliferation, adhesion and migration of the pancreatic adenocarcinoma cell line SW1990. The overexpression of S518D merlin inhibited the growth of SW1990 and did not affect migration or adhesion. These results suggest that the phosphorylation of ezrin may contribute to the progression of pancreatic carcinoma and that the level of phosphorylated ezrin may serve as an adverse prognostic factor for pancreatic carcinoma. PMID:24728215
Zhou, Jiahua; Feng, Yongjiang; Tao, Ketao; Su, Zhanhai; Yu, Xiaojin; Zheng, Jie; Zhang, Lihua; Yang, Detong
Squamous cell carcinoma of the pancreas
Pancreatic malignancies can be subdivided into endocrine and non-endocrine processes. Of the non-endocrine tumours, ductal carcinoma is the most common, and the ductal carcinomas can be further subdivided into adenocarcinomas and squamous cell carcinomas. The adenocarcinomas constitute most of the non-endocrine pancreatic malignancies, and the treatment options for these, although limited in efficacy, are relatively well established. The squamous cell carcinoma pathology is a rare entity, and few reports of it are found in the literature. As a result, treatment options for squamous cell carcinoma of the pancreas are poorly understood. Here, we report the presentation of a 48-year-old woman with metastatic squamous cell carcinoma of the pancreas. The subsequent investigations, treatment, and outcome are described.
Al-Shehri, A.; Silverman, S.; King, K.M.
Pancreatic cancer remains largely an incurable disease necessitating the development of novel therapeutic approaches. Adoptive immunotherapy using chimeric antigen receptor (CAR)-transduced T cells represents an alternative treatment with curative potential. We present an overview of the engineering of novel CARs targeting prostate stem cell antigen (PSCA), implications for the development of immunotherapies, and potential strategies to circumvent on-target/off-tumor toxicities.
Abate-Daga, Daniel; Rosenberg, Steven A; Morgan, Richard A
Neuroendocrine differentiation antigen on human lung carcinoma and Kulchitski cells.
In the normal lung, a subset of cells with a histological appearance consistent with that of Kulchitski cells are the only lung cells reacting with a monoclonal antibody (MOC-1) raised against a human small cell lung carcinoma-derived cell line. Outside the lung, a subset of normal endocrine cells (in the adrenal, thyroid, ovary, and pancreas) as well as neural cells (brain and peripheral Schwann cells) also express the antigen detected by MOC-1 (named MOC-1-related antigen). Some of these positively reacting cells are ectodermally derived, whereas others are of proven endodermal origin, indicating that the MOC-1-related antigen is not a cell lineage-specific antigen. Instead, the common expression of the antigen by cells with a neural, endocrine, or neuroendocrine function suggests that the antigen related to a neuroendocrine differentiation state of these cells. The presence of the MOC-1-related antigen on several non-lung tumors mostly paralleled its normal tissue distribution, indicating that the antigen is generally retained upon malignant transformation. In lung carcinoma, the antigen proves to be present on almost all small cell carcinomas tested. In addition, adenocarcinoma and mixed adenosquamous carcinoma could also express the antigen, whereas pure squamous cell carcinoma generally did not. This finding will be discussed in relation to a proposed "common stem cell" histogenesis of lung carcinoma. PMID:2859106
de Leij, L; Poppema, S; Nulend, J K; ter Haar, A; Schwander, E; Ebbens, F; Postmus, P E; The, T H
Autoimmune pancreatitis can develop into chronic pancreatitis.
Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922
Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki
Autoimmune pancreatitis can develop into chronic pancreatitis
Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung�s and Santorini�s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.
The Epidemiology of Pancreatitis and Pancreatic Cancer
Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients� quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer.
Yadav, Dhiraj; Lowenfels, Albert B.
Treatment of Alcoholic Pancreatitis
Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. The majority of cases in the Western world are related to alcohol consumption. Treatment of alcoholic chronic pancreatitis has been difficult, since the mechanisms of disease progression and the causes of pain are poorly understood. The conservative management of chronic pancreatitis focuses on (a) avoidance
Roland H. Pf�tzer; Alexander Schneider
Pancreatic polypeptide secretion
Pancreatic polypeptide, a 36-amino peptide, is released from the pancreas by a variety of stimuli, including intravenous Boots secretin. Studies in a generalized destructive and inflammatory process such as chronic pancreatitis have revealed a markedly diminished response to stimulation. To assess whether pancreatic polypeptide release in response to Boots secretin provides a useful measure of pancreatic destruction in cystic fibrosis,
A. Stern; G. P. Davidson; C. P. Kirubakaran; J. Deutsch; A. Smith; J. Hansky
Cell membrane and cytoplasmic epidermal growth factor receptor expression in pancreatic ductal adenocarcinoma
The significance of over-expression of epidermal growth factor receptor (EGFR) in pancreatic carcinoma is unclear. In this\\u000a study, we examined the association between EGFR over-expression (membranous and cytoplasmic), the associated histopathologic\\u000a features and clinical outcomes in post-resection pancreatic cancer patients. EGFR expression was determined immunohistochemically\\u000a in 90 patients who underwent resection for pancreatic cancer. Cytoplasmic expression was considered positive if
Amit Mahipal; Mary J. Mcdonald; Agnieszka Witkiewicz; Brian I. Carr
Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses
Pancreatic cancer is an aggressive, rapidly fatal disease against which current nonsurgical therapy has minimal impact. This\\u000a study evaluates the efficacy of two novel, replication-competent, multimutated herpes viruses (G207 and NV1020) in an experimental\\u000a model of pancreatic cancer. Four human pancreatic carcinoma cell lines were exposed to G207 or NV1020, and cell survival and\\u000a viral progeny production were determined. Flank
Priscilla F. McAuliffe; William R. Jarnagin; Paul Johnson; Keith A. Delman; Howard Federoff; Yuman Fong
Peroxisome Proliferator-Activated Receptor Gamma and Regulations by the Ubiquitin-Proteasome System in Pancreatic Cancer
Pancreatic cancer is one of the most lethal forms of human cancer. Although progress in oncology has improved outcomes in many forms of cancer, little progress has been made in pancreatic carcinoma and the prognosis of this malignancy remains grim. Several molecular abnormalities often present in pancreatic cancer have been defined and include mutations in K-ras, p53, p16, and DPC4 genes. Nuclear receptor Peroxisome Proliferator-Activated Receptor gamma (PPAR?) has a role in many carcinomas and has been found to be overexpressed in pancreatic cancer. It plays generally a tumor suppressor role antagonizing proteins promoting carcinogenesis such as NF-?B and TGF?. Regulation of pathways involved in pancreatic carcinogenesis is effectuated by the Ubiquitin Proteasome System (UPS). This paper will examine PPAR? in pancreatic cancer, the regulation of this nuclear receptor by the UPS, and their relationship to other pathways important in pancreatic carcinogenesis.
Stravodimou, Athina; Mazzoccoli, Gianluigi; Voutsadakis, Ioannis A.
Erythema ab igne in chronic pancreatic pain: a diagnostic sign.
Two patients with severe chronic pain of pancreatic origin are described. In both there was severe back pain and an area of erythema ab igne lay directly over the portion of the pancreas giving rise to the pain. In both patients therapy directed at these areas of diseased pancreas resulted in relief of symptoms. The presence of erythema ab igne on a patient's back at the level of T12-L2 should arouse suspicion of underlying pancreatic pathology, and this may be valuable in a disease with remarkably little to find on clinical examination. In one patient early obstruction of the pancreatic duct by pancreatic carcinoma caused distal chronic pancreatitis and back pain many months before the onset of obstructive jaundice. Images Figure 1. A Figure 1. B Figure 2. A Figure 2. B
Mok, D W; Blumgart, L H
Epidermal Growth Factor Receptor Inhibition Strategies in Pancreatic Cancer: Past, Present and the Future
Summary Pancreatic carcinoma is an unusually lethal disease and to date treatment with standard chemotherapy has yielded disappointing results. The epidermal growth factor receptor (EGFR) is known to be over-expressed in pancreatic cancer and there is data to suggest that this molecular characteristic may be a poor prognostic factor as it may denote a more aggressive form of the disease.
Michael Cohenuram; Muhammad Wasif Saif
The value of imaging techniques in the staging of pancreatic cancer
Background: The aim of this study was to assess the clinical value of endoscopic ultrasound (EUS) in the staging of pancreatic carcinoma and to compare it to ultrasonography (US) and CT. Methods: We evaluated 45 patients (21 women and 24 men with a mean age of 62.1 years) who had undergone surgical treatment for pancreatic cancer between 1994 and 2004.
J. Kulig; T. Popiela; A. Zaj?c; S. K??k; P. Ko?odziejczyk
Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
How Is Pancreatic Cancer Staged?
... Topic Pancreatic cancer survival by stage How is pancreatic cancer staged? The stage of a pancreatic cancer (extent ... M1: Distant metastasis is present. Stage grouping for pancreatic cancer After the T, N, and M categories of ...
Pancreatic sarcoidosis discovered during Whipple procedure
Pancreatic sarcoidosis is a rare variant of systemic sarcoidosis, with cases described in literature as recently as January 2010. We present here a case of pancreatic involvement with non-caseating granulomas discovered on laparotomy in a patient with a preoperative diagnosis of pancreatic carcinoma. Computer tomography scan without contrast revealed a well-marginated smooth-shaped tumor in the head of the pancreas morphologically consistent with malignancy. During Whipple procedure, the mass was found to be a large lymph node that contained numerous non-caseating granulomas. Radiologically and clinically, non-caseating granulomas of the pancreas are often misdiagnosed as malignant tumor. Special attention given to this differential diagnosis by surgeons, pathologists and clinicians can avoid misdiagnosis and unnecessary treatment.
Cook, Jonathan; Spees, Tanner; Telefus, Phillip; Ranaudo, Jeffrey M.; Carryl, Stephen; Xiao, Philip
Squamous cell carcinoma variants of the upper aerodigestive tract: a comprehensive review with a focus on genetic alterations.
Context.- Squamous cell carcinoma of the upper aerodigestive tract is a heterogenous entity. Although conventional squamous cell carcinomas are easily recognized, the morphologic variants of squamous cell carcinoma can present a diagnostic challenge. Familiarity with these variants is necessary because many are associated with unique risk factors and are characterized by specific molecular alterations (eg, nuclear protein in testis midline carcinomas). Perhaps the most important distinction is in identifying viral-related from nonviral-related carcinomas. The accurate diagnosis of these variants is necessary for prognostic and therapeutic reasons. Objectives.- To provide a clinicopathologic overview and summary of the molecular alterations of the common squamous cell carcinoma variants, including verrucous, spindle cell, acantholytic, adenosquamous, basaloid, and papillary squamous cell carcinoma, as well as nuclear protein in testis midline carcinoma, and to discuss the distinguishing features of human papillomavirus- and Epstein-Barr virus-related squamous cell carcinomas. Data Sources.- Published peer-reviewed literature. Conclusions.- Familiarity with squamous cell carcinoma variants is essential for proper diagnosis and to guide appropriate clinical management. Further insight into the molecular alterations underlying those variants may lead to alterations in existing treatment approaches and to evolution of novel treatment modalities. PMID:24878013
Shah, Akeesha A; Jeffus, Susanne K; Stelow, Edward B
Use of pancreatic schilling test to determine efficiency of pancreatic enzyme delivery in pancreatic insufficiency
The pancreatic Schilling test (PST), a noninvasive, sensitive pancreatic function test, was studied to determine its ability to detect pancreatic proteolytic enzyme replacement in patients with pancreatic insufficiency. Seven subjects with welldocumented pancreatic insufficiency and an abnormal PST consistent with pancreatic insufficiency were studied with three enzyme regimens: (1) Viokase (four tablets), (2) Pancrease (three capsules), and (3) Pancrease (10
W. R. Brugge; H. J. Goldberg; C. A. Burke; B. J. Depping
Genetic Mutations Associated With Cigarette Smoking in Pancreatic Cancer
Background Cigarette smoking doubles the risk of pancreatic cancer and smoking accounts for 20 to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provides an unprecedented opportunity to identify mutational patterns associated with smoking. Design We previously sequenced over 750 million base pairs of DNA from 23,219 transcripts in 24 adenocarcinomas of the pancreas (�Discovery Screen�). In this previous study the 39 genes that were mutated more than once in the Discovery Screen were sequenced in an additional 90 adenocarcinomas of the pancreas (�Validation Screen�). Here we compared the somatic mutations in the cancers obtained from individuals who ever smoked cigarettes (n=64) to the somatic mutations in the cancers obtained from individuals who never smoked cigarettes (n=50). Results When adjusted for age and gender, analyses of the Discovery Screen revealed significantly more non-synonymous mutations in the carcinomas obtained from ever smokers (mean 53.1 mutations per tumor, SD 27.9) than in the carcinomas obtained from never smokers (mean 38.5, SD 11.1, p=0.04). The difference between smokers and non-smokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, p16/CDKN2A and SMAD4), but instead was predominantly observed in genes mutated at lower frequency. No differences were observed in mutations in carcinomas from the head vs. tail of the gland. Conclusion Pancreatic carcinomas from cigarette smokers harbor more mutations than do carcinomas from never smokers. The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer.
Blackford, Amanda; Parmigiani, Giovanni; Kensler, Thomas W.; Wolfgang, Christopher; Jones, Sian; Zhang, Xiaosong; Parsons, D. Willams; Lin, Jimmy Cheng-Ho; Leary, Rebecca J.; Eshleman, James R.; Goggins, Michael; Jaffee, Elizabeth M.; Iacobuzio-Donahue, Christine A.; Maitra, Anirban; Klein, Alison; Cameron, John L.; Olino, Kelly; Schulick, Richard; Winter, Jordan; Vogelstein, Bert; Velculescu, Victor E.; Kinzler, Kenneth W.; Hruban, Ralph H.
Analysis of whole genomic expression profiles and screening of the key signaling pathways associated with pancreatic cancer
The tumorigenesis of pancreatic cancer is thought to be a complex process. Investigation of the molecular mechanism of pancreatic cancer and exploring the specific markers for early diagnosis and specific targets of therapy is a key point to prevent and treat pancreatic cancer effectively and to improve their prognosis. In this study, expression profiles experiment was performed using Agilent human whole genomic oligonucleotide microarrays with 41,000 genes. Differentially expressed genes related with pancreatic cancer were screened, and analyzed further by GO term analysis and KEGG Pathway analysis. Our results showed that there were 1276 differentially expressed genes associated with pancreatic cancer. 691 genes were up regulated and 585 were down regulated in pancreatic cancer group. The present study confirmed that the occurrence of pancreatic cancer was involved in multiple-gene interaction. In addition, our study found that pancreatic cancer was related to an activation of the mTOR signaling pathway and renal cell carcinoma pathway.
He, Chengzhi; Jiang, Hua; Geng, Shasha; Sheng, Haihui; Shen, Xiaoying; Zhang, Xiaoyan; Zhu, Shizhang; Chen, Ximei; Yang, Changqing; Gao, HengJun
Chronic Pancreatitis in Children
... of acute pancreatitis. Not all patients with a genetic predisposition or anatomic abnormalities will develop chronic pancreatitis. The reason for the variability is that modifying factors act in concert with ...
Cryosurgery for pancreatic cancer
The procedure of pancreatic cryosurgery is performed with intraoperative or percutaneous approaches. Based on current data and our initial experience, cryoablation appears to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. It is suggested that there are almost no known contraindications to the use of cryosurgery for pancreatic cancer. For most patients with pancreatic cancer, cryosurgery can substitute conventional surgery.
Xu, Kecheng; Yang, Daming
Pancreatitis from Metastatic Small Cell Lung Cancer: Successful Treatment with Endoscopic Intrapancreatic Stenting
Lung cancer metastases can occur in almost any organ. However, metastasis of small cell lung cancer to the pancreas is rare. Moreover, not all cases present with clinically diagnosed pancreatitis. We recently treated a patient with small cell lung carcinoma that invaded the pancreatic duct causing acute pancreatitis. Generally, the treatment for tumor-induced acute pancreatitis is initially supportive followed by aggressive chemotherapy or surgery. If the patient can tolerate the insertion of an endoscopic intrapancreatic stent, this is performed in addition to chemotherapy and surgery; this approach offers a safe and effective treatment modality for such patients.
Woo, Jong-Shin; Woo, Yong Sik; Jang, Jae Young; Chang, Young Woon; Lee, Joung Il; Chang, Rin
Experimental Models of Pancreatitis
Acute pancreatitis is an inflammatory disease characterized by interstitial edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its severity. Regardless of the extent of tissue injury, acute pancreatitis is a completely reversible process with evident normal tissue architecture after recovery. Its pathogenic mechanism has been known to be closely related to intracellular digestive enzyme activation. In contrast to acute pancreatitis, chronic pancreatitis is characterized by irreversible tissue damage such as acinar cell atrophy and pancreatic fibrosis that results in exocrine and endocrine insufficiency. Recently, many studies of chronic pancreatitis have been prompted by the discovery of the pancreatic stellate cell, which has been identified and distinguished as the key effector cell of pancreatic fibrosis. However, investigations into the pathogenesis and treatment of pancreatitis face many obstacles because of its anatomical location and disparate clinical course. Due to these difficulties, most of our knowledge on pancreatitis is based on research conducted using experimental models of pancreatitis. In this review, several experimental models of pancreatitis will be discussed in terms of technique, advantages, and limitations.
Hyun, Jong Jin
Pancreatic Ductal Adenocarcinoma
Because pancreatic cancer is often diagnosed at a late stage, surgical removal of the tumor or the organ is often difficult, if not impossible. Pancreatic ductal adenocarcinoma, or PDAC, is by far the most common type of pancreatic malignancy. PDAC is distinct from other cancers due to the biological barrier the tumor builds around itself.
Experimental models of pancreatitis.
Acute pancreatitis is an inflammatory disease characterized by interstitial edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its severity. Regardless of the extent of tissue injury, acute pancreatitis is a completely reversible process with evident normal tissue architecture after recovery. Its pathogenic mechanism has been known to be closely related to intracellular digestive enzyme activation. In contrast to acute pancreatitis, chronic pancreatitis is characterized by irreversible tissue damage such as acinar cell atrophy and pancreatic fibrosis that results in exocrine and endocrine insufficiency. Recently, many studies of chronic pancreatitis have been prompted by the discovery of the pancreatic stellate cell, which has been identified and distinguished as the key effector cell of pancreatic fibrosis. However, investigations into the pathogenesis and treatment of pancreatitis face many obstacles because of its anatomical location and disparate clinical course. Due to these difficulties, most of our knowledge on pancreatitis is based on research conducted using experimental models of pancreatitis. In this review, several experimental models of pancreatitis will be discussed in terms of technique, advantages, and limitations. PMID:24944983
Hyun, Jong Jin; Lee, Hong Sik
High-risk cutaneous squamous cell carcinoma.
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and its incidence has increased in recent decades. Most cSCCs are successfully treated by surgery, but local and distant metastases develop in approximately 5% of cases; this proportion is higher in certain forms of cSCC with high-risk factors, namely: tumor size >2cm, depth >2mm, Clark level ?IV, perineural invasion, lymphovascular invasion, poor differentiation, certain histologic subtypes (desmoplastic or adenosquamous carcinoma, invasive Bowen disease, or a cSCC arising in areas of chronic inflammation), immunosuppression, human papillomavirus infection, high-risk anatomic location (pinna of the ear, labial mucosa), expression of certain tumor genes, and inadequate tumor resection. The latest TNM (tumor, lymph node, metastasis) classification of cSCC published by the American Joint Committee on Cancer (AJCC) in the seventh edition of its Cancer Staging Manual now incorporates several of these risk factors to improve disease staging. We review all the factors currently considered to be markers of poor prognosis in cSCC and analyze the new AJCC classification and the different treatment options for high-risk cSCC. PMID:22261673
Nu�o-Gonz�lez, A; Vicente-Mart�n, F J; Pinedo-Moraleda, F; L�pez-Estebaranz, J L
Risk of pancreatic adenocarcinoma in chronic pancreatitis
Background: The risk of pancreatic cancer in patients with chronic pancreatitis (CP) is difficult to assess. Previous studies, mostly case control studies or studies relying on data case registers, reported relative risks varying from 2.3 to 18.5. Methods: We studied a prospective, single centre, medical-surgical cohort of 373 consecutive patients (322 (86%) men, median age 40 years) with proven CP (alcoholic origin 85%) and a follow up of at least two years (median follow up 9.2 years; range 2.0�34.8) in order to exclude pancreatitis revealing pancreatic cancer. We calculated the age and sex standardised incidence ratio (SIR) as the ratio of the number of observed cases of pancreatic cancer in this cohort to the number of expected cases, as provided by the French National Cancer Register. Results: Four cases of pancreatic adenocarcinoma (1.1% of patients) were observed in 3437 patient years (expected number of cases 0.15; SIR 26.7, 95% confidence interval (CI) 7.3�68.3; p=0.00002). In a second analysis in which patients lost to follow up were considered to be followed up until the end point without having developed pancreatic adenocarcinoma (4762 patient years), SIR was 19.0 (CI 5.2�48.8; p=0.00007). Conclusion: Patients with CP have a markedly increased risk of pancreatic cancer compared with the general population.
Malka, D; Hammel, P; Maire, F; Rufat, P; Madeira, I; Pessione, F; Levy, P; Ruszniewski, P
The Medical Management of Pancreatic Cancer: A Review
Pancreatic carcinoma is a commonly occurring can- cer that tends to present late in its course when poten- tially curative surgical treatment is not possible. The majority of patients are, therefore, candidates for sys- temic therapy. We review the patient and disease- related factors that contribute to the difficulties in the medical management of this condition and discuss new methods
Pancreatic cancer genomics: insights and opportunities for clinical translation
Pancreatic cancer is a highly lethal tumor type for which there are few viable therapeutic options. It is also caused by the accumulation of mutations in a variety of genes. These genetic alterations can be grouped into those that accumulate during pancreatic intraepithelial neoplasia (precursor lesions) and thus are present in all cells of the infiltrating carcinoma, and those that accumulate specifically within the infiltrating carcinoma during subclonal evolution, resulting in genetic heterogeneity. Despite this heterogeneity there are nonetheless commonly altered cellular functions, such as pathways controlling the cell cycle, DNA damage repair, intracellular signaling and development, which could provide for a variety of drug targets. This review aims to summarize current knowledge of the genetics and genomics of pancreatic cancer from its inception to metastatic colonization, and to provide examples of how this information can be translated into the clinical setting for therapeutic benefit and personalized medicine.
Pancreatic cancer risk in hereditary pancreatitis
Inflammation is part of the body's immune response in order to remove harmful stimuli�like pathogens, irritants or damaged cells�and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis (HP) is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. HP often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of HP patients to develop pancreatic cancer.
Weiss, Frank U.
Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer.
Poston, G J; Gillespie, J; Guillou, P J
The pathogenesis of chronic pancreatitis.
To date, there is no consensus on the evolution of chronic pancreatitis. Comfort's initial proposal of acute pancreatitis progressing to chronic pancreatitis was discarded by protagonists of the 'separate' theory. Sarles thus stresses the de novo evolution of chronic pancreatitis-acinar protein hypersecretion associated with an imbalance of pancreatic stone promoting and inhibiting factors. However, the 'necrosis-fibrosis sequence' hypothesis of Kloppel and Mallet resurrects the probability of acute pancreatitis leading to chronic pancreatitis. Dimagno offers a unifying concept that the degree of acinar injury determines the natural history of pancreatitis. Uninhibited release of toxic free radicals could be a common end point for various aetiologies resulting in acute or chronic pancreatitis. The pathogenesis of chronic calcifying pancreatitis of the tropics is possibly no different from alcoholic chronic pancreatitis. Neurocrine and paracrine mechanisms have been offered to explain pain out of proportion to radiological and histological pancreatic abnormalities in minimal change chronic pancreatitis.
Sidhu, S. S.; Tandon, R. K.
Inherited Pancreatic Cancer Syndromes
Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1 and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.
Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C
Endoscopic treatment of chronic pancreatitis
Treatment of chronic pancreatitis has been exclusively surgical for a long time. Recently, endoscopic therapy has become widely used as a primary therapeutic option. Initially performed for drainage of pancreatic cysts and pseudocysts, endoscopic treatments were adapted to biliary and pancreatic ducts stenosis. Pancreatic sphincterotomy which allows access to pancreatic ducts was firstly reported. Secondly, endoscopic methods of stenting, dilatation,
Laurent Heyries; Jose Sahel
Chemotherapeutic gemcitabine doublets in pancreatic carcinoma.
Single-agent gemcitabine remains the standard treatment for advanced pancreas cancer. Results of four phase III trials reported in 2004 indicated no survival benefit for single-agent exatecan or combinations of exatecan, pemetrexed, and oxaliplatin with gemcitabine compared with gemcitabine alone. It is unclear whether a trend toward improved outcome with the gemcitabine/oxaliplatin combination was attributable to use of a fixed-dose rate infusion regimen of gemcitabine in the combination arm, a method of administration that appears to be associated with benefits compared with standard gemcitabine infusion. Novel approaches to treatment currently under investigation include refining schedules of administration of combination therapy, combining gemcitabine with molecular targeted therapy, and combining gemcitabine with low-molecular-weight heparin. PMID:16143162
Richards, Donald A
Current Treatment Options for Pancreatic Carcinoma
Pancreas cancer is a significant cause of cancer mortality; therefore, the development of early diagnostic strategies and\\u000a effective treatment is essential. Improvements in imaging technology, as well as use of biomarkers such as CA 19�9, are changing\\u000a the way that pancreas cancer is diagnosed and staged. Although progress in treatment for pancreas cancer has been incremental,\\u000a development of combination therapies
Emily Castellanos; Jordan Berlin; Dana Backlund Cardin
[Vasoactive polypeptide-producing pancreatic carcinoma].
Authors report a case of Verner-Morrison syndrome which occurred in a 75-year-old man. The syndrome was caused by a pancreas VIP-oma with the histological structure of adenocarcinoma. Treatment with somatostatin analogous (octreotid) was effective, but the outcome was lethal due to subsequent pulmonary embolism. PMID:7566933
Gr�czi, K; K�ronya, P; Krutsay, M
Pancreatic ductal adenocarcinoma with autoimmune pancreatitis-like histologic and immunohistochemical features.
Autoimmune pancreatitis (AIP) often manifests as a mass lesion causing obstructive jaundice, clinically mimicking pancreatic carcinoma. A diagnosis of AIP may obviate the need for surgical resection, as most patients respond to steroid treatment. However, it is not clear whether these 2 conditions can coexist. In this study, 105 specimens resected for pancreatic ductal adenocarcinoma (PDAC) that also have changes of chronic pancreatitis were examined for features considered to be characteristic of AIP. Of 105 cases of PDAC with changes of chronic pancreatitis, 10 (9.5%) exhibited histologic features of AIP, including exuberant fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, or granulocytic epithelial lesions. Of these 10 cases, 7 had more than 20 immunoglobulin G4+ plasma cells per high-power field. Of these 7 cases, 5 were analyzed for Kirsten rat sarcoma viral oncogene mutation and SMAD4 expression. Three cases showed K-ras mutation and/or loss of SMAD4 expression in benign AIP-like areas. These findings suggest 2 possibilities: first, AIP-like lesions may occur in a small but significant portion of PDAC cases; second, some PDACs may arise in a background of AIP. Therefore, caution is necessary when making a diagnosis of AIP by needle biopsy of a mass lesion, and patients with a tentative AIP diagnosis should be closely followed up clinically. PMID:24457081
Zhang, Xuefeng; Liu, Xiuli; Joseph, Loren; Zhao, Lei; Hart, John; Xiao, Shu-Yuan
[Pancreatitis in pregnant women].
Regardless of the fact, that pancreatitis during pregnancy is rare; this disease is characterized by high indices of maternal and perinatal mortality. Among variety of etiological and pathogenetic aspects of pregnant women's acute pancreatitis, leading role in its development belongs to bile-excreting system diseases, conditioned by physiological processes in women's organism during gestational period. Also there is a genetic theory of acute pancreatitis genesis in pregnant women, based on dislipoproteinemia development caused by lipoprotein lipase insufficiency, when severity of pancreatitis course is correlated with morphotype of this enzyme gene mutation. Chronic pancreatitis is conditioned by the same causes and can develop and recur during pregnancy and right after parturition. Diagnostics of pregnant women's pancreatitis is complicated because of limitation of the use of some methods (radiation and endoscopic). Pancreatitis clinical course does not differ from the one in nonpregnant women and is manifested by pain abdominal and dyspeptic syndromes, and also by syndromes of exocrine and endocrine pancreatic insufficiency. The main clinical feature of pregnant women's pancreatitis is high occurrence of painless forms. Approaches to treatment include pain relief disintoxication, use of pancreatic secretion blockers, multienzyme complexes, glycemia correction. PMID:18720707
Maev, I V; Burkov, S G; Kucheriavy?, Iu A; Ovlashenko, E I
Chronic Pancreatitis (Beyond the Basics)
... Irritable bowel syndrome (Beyond the Basics) Patient information: Pancreatic cancer (Beyond the Basics) Clinical manifestations and diagnosis of ... of the upper intestine ? An increased risk of pancreatic cancer PANCREATITIS DIAGNOSIS It can be difficult to diagnose ...
... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 2A View/Download: Small: 720x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 2A Description: Stage IIA pancreatic cancer; drawing ...
... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 2B View/Download: Small: 720x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 2B Description: Stage IIB pancreatic cancer; illustration ...
Pancreolauryl test in chronic pancreatitis
Summary The pancreolauryl test was performed in 30 subjects with chronic pancreatitis, in order to evaluate its behavior in relation to the duration of the clinical history and the presence of pancreatic calcifications, diabetes mellitus, jaundice, and pancreatic pseudocysts.
A. Panucci; C. Angonese; G. Del Favero; C. Fabris; L. Marchioro; D. Basso; F. Di Mario; R. Naccarato
Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas.
Epithelial-to-mesenchymal transition (EMT) is believed to contribute to tumour invasion. Vimentin expression by carcinoma cells is a largely recognized marker of EMT. This study aimed at examining vimentin expression in non small cell lung carcinomas (NSCLC) by immunohistochemistry to evaluate potential correlations between vimentin expression and the differentiation status, the TNM stage and the outcome of the patients. 295 NSCLC including 164 squamous cell carcinomas (SCC), 108 adenocarcinomas (AC) and 23 other NSCLC carcinomas have been examined by immunohistochemistry. Vimentin was indeed detected in 145 cases (49.2%). It was principally present in isolated tumour cells and invasive clusters, particularly in cells at the tumour/stroma interface. Vimentin expression was significantly more expressed in large cell neuroendocrine, adeno-squamous and sarcomatoid carcinomas than in SCC and AC and was significantly associated with the differentiation status of carcinomas. The follow-up of 193 patients further demonstrated that an extensive expression of vimentin (>50% of tumour cells) was associated with the occurrence of metastases. In conclusion, our data demonstrate that vimentin expression is a frequent event in NSCLC and that its expression can be associated with a lack of differentiation and the occurrence of metastases. PMID:23562674
Dauphin, Maryline; Barbe, Coralie; Lemaire, Sarah; Nawrocki-Raby, B�atrice; Lagonotte, Eymeric; Delepine, Gonzague; Birembaut, Philippe; Gilles, Christine; Polette, Myriam
A case of thyroid metastasis from pancreatic cancer: case report and literature review
Background Thyroid metastases are clinically rare, and usually occur in patients with a history of prior malignancy and when there are metastases elsewhere. Metastases of pancreatic carcinoma to the thyroid are extremely rare, with only three cases reported in the literature. Case presentation We report a patient who had a pancreatic carcinoma with metastasis to the thyroid as initial clinical presentation of the disease. A 63-year-old man with a history of weight loss and fatigue presented with cervical lymphadenopathies and a large nodule in the right lobe of the thyroid. A fine needle aspiration of the nodule gave inconclusive cytological results for the origin of the neoplastic cells. An ultrasound-guided core biopsy revealed the presence of a poorly differentiated adenocarcinoma infiltrating the thyroid with atrophic thyroid follicles. Immunohistochemical staining of the lesion was strongly positive for Cytokeratin 19 suggesting a pancreatic origin of the metastasis. A contrast CT scan demonstrated an enlargement of the pancreatic body, dilatation of the pancreatic duct, diffuse retroperitoneal, paraaortic and cervical lymphadenopathy and secondary lesions in the liver. Conclusion Metastases to the thyroid from pancreatic carcinoma are extremely rare. A core biopsy of the lesion excluded a thyroid carcinoma and permitted the diagnosis of the primary neoplasm.
MicroRNA Expression Aids the Preoperative Diagnosis of Pancreatic Ductal Adenocarcinoma
Objectives To evaluate microRNA (miRNA) expression in pancreatic resection specimens and fine needle aspiration (FNA) biopsies and determine which, if any, miRNAs aid the distinction between benign and malignant pancreatic tumors in limited cytology material. Methods Resection specimens containing adenocarcinoma (n=17), intraductal papillary mucinous neoplasms (IPMN, n=11), and non-neoplastic tissues (n=15) were evaluated for miR-21, -221, -100, -155, and -181b expression by qRT-PCR, and a subset of carcinomas and IPMNs were analyzed with miRNA microarrays. Cellblocks containing carcinoma (n=26) or benign pancreatic lesions (n=11) from FNA biopsies were subjected to qRT-PCR for miR-21, miR-221, miR-181b, miR-196a and miR-217. Results Carcinomas showed higher expression of miR-21, -221, -155, -100, and -181b than benign lesions by qRT-PCR and overexpression of miR-21, -221, and-181b was confirmed by microarray analysis. Cellblocks containing carcinoma showed higher expression of miR-21, -221, and -196a than those from benign lesions (p<0.001, p=0.009, p<0.001, respectively). Conclusions Pancreatic ductal adenocarcinomas show differential expression of miRNAs compared to benign pancreatic lesions. A select panel of miRNAs aids the distinction between pancreatic lesions in cytology specimens.
Panarelli, Nicole C.; Chen, Yao-Tseng; Zhou, Xi K.; Kitabayashi, Naoki; Yantiss, Rhonda K.
[Rare solid pancreatic tumors].
The most common tumor of the pancreas is cancer, which constitutes 85% of all pancreatic neoplasms. Cystic pancreatic tumors comprise 10% of malignancies. No more than 5% of pancreatic tumors are rare solid tumors as: neuroendocrine tumors, gastrointestinal stromal tumors, solid pseudopapillary tumors, pecomas, lymphomas, granulocytic sarcomas, schwannomas, lipomas, liposarcomas and metastases to pancreas. Nowadays, these tumors are diagnosed more commonly due to the developement and accessibility of the diagnostic imaging techniques. Moreover, the treatment and management of rare solid pancreatic tumors often differs from the management in pancreatic cancer what makes the differential diagnosis difficult and responsible challenge. The main purpose of this article is to present an actual data of epidemiology, clinical presentation, management and treatment of rare solid pancreatic tumors according to recent literature and self experience. PMID:24052992
Dabkowski, Krzysztof; Kojder, Klaudyna; Smereczy?ski, Andrzej; Lubikowski, Jerzy; Patalan, Marek; Starzy?ska, Teresa
Acute Pancreatitis (Beyond the Basics)
... WHERE TO GET MORE INFORMATION REFERENCES GRAPHICS FIGURES Pancreas anatomy PANCREATITIS OVERVIEW Acute pancreatitis refers to inflammation of the pancreas, causing sudden and severe abdominal pain. The pancreas ...
Smoking and Pancreatic Disease
Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.
Edderkaoui, Mouad; Thrower, Edwin
Pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Detailed\\u000a information about the findings of previous studies concerning post-ERCP pancreatitis has not been utilized sufficiently. The\\u000a purpose of the present article was to present guidelines for the diagnostic criteria of post-ERCP pancreatitis, and its incidence,\\u000a risk factors, and prophylactic procedures that are supported by evidence. To achieve
Shinju Arata; Tadahiro Takada; Koichi Hirata; Masahiro Yoshida; Toshihiko Mayumi; Morihisa Hirota; Masamichi Yokoe; Masahiko Hirota; Seiki Kiriyama; Miho Sekimoto; Hodaka Amano; Keita Wada; Yasutoshi Kimura; Toshifumi Gabata; Kazunori Takeda; Keisho Kataoka; Tetsuhide Ito; Masao Tanaka
Diagnosis of Chronic Pancreatitis
The diagnosis of chronic pancreatitis (CP) is usually suspected on the basis of suggestive signs and symptoms, but the clinical\\u000a presentation alone is rarely specific enough to reach a diagnosis. The diagnosis requires confirmation by diagnostic tests\\u000a that measure perturbations of either pancreatic structure or pancreatic function. In the majority of patients, the disease\\u000a is suspected based on the presence
Chris E. Forsmark
Screening for Pancreatic Cancer
Despite improvements in the clinical and surgical management of pancreatic cancer, limited strides have been made in the early detection of this highly lethal malignancy. The majority of localized pancreatic tumors are asymptomatic, and the recognized presenting symptoms of pancreatic adenocarcinoma are often vague and heterogeneous in nature. These factors, coupled with the lack of a sensitive and noninvasive screening method, have made population-based screening for pancreatic cancer impossible. Nevertheless, at least two large institutions have performed multimodality-screening protocols for individuals with high risk of pancreatic cancer based on genetic predisposition and strong family history. Abnormalities noted during these screening protocols prompted further investigation or surgery that resulted in the discovery of benign, potentially malignant, and malignant pancreatic lesions. In addition to ductal epithelial pancreatic intraepithelial neoplasia, greater sensitivity has recently been achieved in the identification and characterization of precancerous mucinous pancreatic tumors. Advancements in proteomics and DNA microarray technology may confirm serum-based biomarkers that could be incorporated into future screening algorithms for pancreatic cancer.
Brand, Randall E.
An evaluation of echography in the diagnosis of pancreatic disease.
In the present study an attempt to evaluate the efficacy of echography as a diagnostic tool has been made. A total of 52 patients (chronic pancreatitis (42); pancreatic cysts (three); and carcinoma of the pancreas (seven)) were studied and the results compared with those from other diagnostic techniques. In 65.7% of chronic pancreatitis patients, and in all cases of carcinoma of the pancreas, echography provided evidence of pancreatic abnormality but in no case could an unambiguous diagnosis of the disease be made. However, in all cases of pancreatic cyst, echography gave precise and unequivocal diagnostic information. There was good agreement between the echographic picture and surgical findings. Cholangiography and duodenography indicated duodenal and choledochal compression in a high proportion of cases in which echography revealed enlargement of the head of the pancreas. It is concluded that echography is a simple, safe, and valuable addition to the techniques available for studying the pancreas. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8
Fontana, G; Bolondi, L; Conti, M; Plicchi, G; Gullo, L; Caletti, G C; Labo, G
Aspiration biopsy of carcinoma of the pancreas.
Peroperative pancreatic aspiration biopsies were performed on 21 patients with pancreatic lesions using a standard 20-ml disposable syringe and a 21-gauge needle. No complications were recorded which could be attributed to this procedure. A further 10 aspiration biopsies were carried out on postmortem specimens in an attempt to determine the accuracy of this method in the diagnosis of carcinoma of the pancreas. It is concluded that peroperative pancreatic needle biopsy is a safe procedure which is easily performed without special instruments. In can be of enormous value to the surgeon in planning the treatment of patients with pancreatic lesions. In cases where there is an operable mass in the pancreas it offers a simple and quick method of determining the presence of malignant cells and thus definitive surgery may be performed with confidence. For the inoperable cases it offers a method of histological confirmation of the operative findings.
Shorey, B A
Celiac axis stenosis in pancreatic head resection for chronic pancreatitis
Background and aims. To determine the outcome of pancreatic head resection for chronic pancreatitis in the presence of celiac axis stenosis or occlusion we analyzed the blood supply of the upper abdominal organs in 11 patients before and after surgery. Patients and methods. Between March 1994 and April 2000 we performed 145 pancreatic head resections for chronic pancreatitis. Preoperatively 11
J�rn Pfeiffenberger; Ulrich Adam; Oliver Drognitz; Jens C. Kr�ger; Frank Makowiec; Wolfgang Schareck; Ulrich T. Hopt
Pancreatitis is a risk factor for pancreatic cancer
Background & Aims: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges since 1970. In taking advantage of this large database, the present study aimed to determine whether pancreatitis is a risk factor for pancreatic cancer. Methods: A case control study compared the occurrence of pancreatitis in 2639 patients with pancreatic cancer and a matched
Pradeep Bansal; Amnon Sonnenberg
Tuberculous lymphadenopathy mimicking pancreatic neoplasm.
Abdominal tuberculosis (TB) is the sixth most common location of extrapulmonary TB involvement. Because its symptoms and signs are often nonspecific, laboratory and imaging findings mimic other diseases including carcinoma. Therefore, the diagnosis of abdominal TB is challenging. We herein report a case of 74-year-old woman who presented with abdominal pain, anorexia, and weight loss. She had been given a diagnosis of pancreatic head carcinoma. Laboratory data was unremarkable except for elevated erythrocyte sedimentation rate, CA125, and sIL-2R. CT scan revealed multiple enlarged peripancreatic lymph nodes and concentric thickening of the ileocecal wall. Colonoscopy demonstrated deformed ileocecal valve and erosions. Histological examination showed epithelioid granulomas. Laparoscopy revealed numerous white tubercles diffusely covering the parietal peritoneum. Histopathological images of peripancreatic lymph node revealed large multiple caseating granulomas surrounded by Langhans_giant cells and epithelioid cells. Polymerase chain reaction and culture of the specimens were positive for Mycobacterium tuberculosis. Tuberculous lymphadenopathy, colitis, and peritonitis were finally diagnosed. She responded well to the antitubercular treatment. PMID:22851977
Hoshino, Kunikazu; Arakaki, Shingo; Shibata, Daisuke; Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Fukunori; Shiraishi, Masayuki; Nishimaki, Tadashi; Fujita, Jiro
Tuberculous Lymphadenopathy Mimicking Pancreatic Neoplasm
Abdominal tuberculosis (TB) is the sixth most common location of extrapulmonary TB involvement. Because its symptoms and signs are often nonspecific, laboratory and imaging findings mimic other diseases including carcinoma. Therefore, the diagnosis of abdominal TB is challenging. We herein report a case of 74-year-old woman who presented with abdominal pain, anorexia, and weight loss. She had been given a diagnosis of pancreatic head carcinoma. Laboratory data was unremarkable except for elevated erythrocyte sedimentation rate, CA125, and sIL-2R. CT scan revealed multiple enlarged peripancreatic lymph nodes and concentric thickening of the ileocecal wall. Colonoscopy demonstrated deformed ileocecal valve and erosions. Histological examination showed epithelioid granulomas. Laparoscopy revealed numerous white tubercles diffusely covering the parietal peritoneum. Histopathological images of peripancreatic lymph node revealed large multiple caseating granulomas surrounded by Langhans_giant cells and epithelioid cells. Polymerase chain reaction and culture of the specimens were positive for Mycobacterium tuberculosis. Tuberculous lymphadenopathy, colitis, and peritonitis were finally diagnosed. She responded well to the antitubercular treatment.
Hoshino, Kunikazu; Arakaki, Shingo; Shibata, Daisuke; Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Fukunori; Shiraishi, Masayuki; Nishimaki, Tadashi; Fujita, Jiro
Evolution and dynamics of pancreatic cancer progression
Efficient metastasis is believed as the result of multiple genetic, epigenetic and/or post-translational events in the lifetime of a carcinoma. At the genetic level, these events may be categorized into those that occur during carcinogenesis, and those that occur during subclonal evolution. This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs, many features of which can be extrapolated to other solid tumor types. The implications of these findings to personalize genome analyses of an individual patient�s tumor are also discussed.
Yachida, S; Iacobuzio-Donahue, CA
Regulation of pancreatic cancer growth by superoxide.
K-ras mutations have been identified in up to 95% of pancreatic cancers, implying their critical role in the molecular pathogenesis. Expression of K-ras oncogene in an immortalized human pancreatic ductal epithelial cell line, originally derived from normal pancreas (H6c7), induced the formation of carcinoma in mice. We hypothesized that K-ras oncogene correlates with increased non-mitochondrial-generated superoxide (O?2.-), which could be involved in regulating cell growth contributing to tumor progression. In the H6c7 cell line and its derivatives, H6c7er-Kras+ (H6c7 cells expressing K-ras oncogene), and H6c7eR-KrasT (tumorigenic H6c7 cells expressing K-ras oncogene), there was an increase in hydroethidine fluorescence in cell lines that express K-ras. Western blots and activity assays for the antioxidant enzymes that detoxify O?2.- were similar in these cell lines suggesting that the increase in hydroethidine fluorescence was not due to decreased antioxidant capacity. To determine a possible non-mitochondrial source of the increased levels of O?2.-, Western analysis demonstrated the absence of NADPH oxidase-2 (NOX2) in H6c7 cells but present in the H6c7 cell lines expressing K-ras and other pancreatic cancer cell lines. Inhibition of NOX2 decreased hydroethidine fluorescence and clonogenic survival. Furthermore, in the cell lines with the K-ras oncogene, overexpression of superoxide dismutases that detoxify non-mitochondrial sources of O?2.-, and treatment with the small molecule O?2.- scavenger Tempol, also decreased hydroethidine fluorescence, inhibited clonogenic survival and inhibited growth of tumor xenografts. Thus, O?2.- produced by NOX2 in pancreatic cancer cells with K-ras, may regulate pancreatic cancer cell growth. PMID:22392697
Du, Juan; Nelson, Elke S; Simons, Andrean L; Olney, Kristen E; Moser, Justin C; Schrock, Hannah E; Wagner, Brett A; Buettner, Garry R; Smith, Brian J; Teoh, Melissa L T; Tsao, Ming-Sound; Cullen, Joseph J
Pancreatitis was considered a rare disease in the cat until a couple of decades ago when several retrospective studies of severe acute pancreatitis were published. It was apparent that few of the diagnostic tests of value in the dog were helpful in cats. With increasing clinical suspicion, availability of abdominal ultrasonography, and introduction of pancreas-specific blood tests of increasing utility, it is now accepted that acute pancreatitis is probably almost as common in cats as it is in dogs, although the etiology(s) remain more obscure. Pancreatitis in cats often co-exists with inflammatory bowel disease, less commonly with cholangitis, and sometimes with both. Additionally, pancreatitis may trigger hepatic lipidosis, while other diseases, such as diabetes mellitus, may be complicated by pancreatitis. Therapy is similar to that used in dogs, with added emphasis on early nutritional support to prevent hepatic lipidosis. Less is known about chronic pancreatitis than the acute form, but chronic pancreatitis is more common in cats than it is in dogs and may respond positively to treatment with corticosteroids. PMID:23148855
Armstrong, P Jane; Williams, David A
Hyperamylasaemia: pathognomonic to pancreatitis?
An 82-year-old woman, presented with a history of vomiting, abdominal mass and a significantly raised amylase, but no clinical evidence of pancreatitis. Abdominal ultrasound and CT scans showed an ovarian tumour, and no evidence of pancreatitis-as is often associated with a raised amylase. The patient underwent bilateral ovariectomy and hysterectomy and made a good recovery. PMID:24132440
Burden, Sam; Poon, Anna Sau Kuk; Masood, Kausar; Didi, Mohamed
Idiopathic recurrent pancreatitis
The cause of recurrent acute pancreatitis can be identified in the majority of patients. A small group of patients in whom an etiological association is not obvious is characterized as idiopathic recurrent pancreatitis (IRP). During the last seven years, we used endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi (SO) manometric pressure studies to investigate 116 patients initially diagnosed as
Rama P. Venu; Joseph E. Geenen; Walter Hogan; John Stone; G. Kenneth Johnson; Konrad Soergel
Nutrition, Inflammation, and Acute Pancreatitis
Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis.
Petrov, Max
Disruption of the antiproliferative TGF-? signaling pathways in human pancreatic cancer cells
Resistance to TGF-?1 occurred in pancreatic cancer cells suggesting that inactivation of TGF-? inhibitory signaling pathways may play an important role in human pancreatic cancer. The aim of our study was to determine the presence of alterations in the main putative components of the TGF-? inhibitory signaling pathways (p15, Smad4, Smad2, TGF?-RII, CDC25A). A panel of human carcinomas of the
Alberto Villanueva; Carmen Garc�a; Ana Bel�n Paules; M�nica Vicente; Montse Meg�as; Germ�n Reyes; Priam de Villalonga; Neus Agell; Felix Llu�s; Oriol Bachs; Gabriel Capell�
MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells
The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen�restricted Th2-deviated CD4+ T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC�Th2 axis.
Ochi, Atsuo; Nguyen, Andrew H.; Bedrosian, Andrea S.; Mushlin, Harry M.; Zarbakhsh, Saman; Barilla, Rocky; Zambirinis, Constantinos P.; Fallon, Nina C.; Rehman, Adeel; Pylayeva-Gupta, Yuliya; Badar, Sana; Hajdu, Cristina H.; Frey, Alan B.; Bar-Sagi, Dafna
MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells.
The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis. PMID:22908323
Ochi, Atsuo; Nguyen, Andrew H; Bedrosian, Andrea S; Mushlin, Harry M; Zarbakhsh, Saman; Barilla, Rocky; Zambirinis, Constantinos P; Fallon, Nina C; Rehman, Adeel; Pylayeva-Gupta, Yuliya; Badar, Sana; Hajdu, Cristina H; Frey, Alan B; Bar-Sagi, Dafna; Miller, George
Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer1
Background Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and are graduated in grade 1 to 3, whereas grade 3 is classified as carcinoma in situ. Currently, no reliable, noninvasive imaging technique (e.g., ultrasound, computed tomography, magnet resonance imaging) exists to verify PanINs. Methods Recently, a transgenic mouse model of pancreatic cancer was established in which the tumor progression of human pancreatic carcinoma is reproduced. These so-called Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+mice develop PanINs, which transform to invasive growing pancreatic carcinoma. The pancreata of mice of different ages were immunohistochemically stained using ?-GLUT-2 antibodies. Furthermore, mice underwent positron emission tomography (PET)-computed tomography (CT) with 18F-fluorodeoxyglucose (FDG) to evaluate early detection of PanIN lesions. Results An expression of GLUT-2 in murine PanINs was found in PanINs of grade 1B and higher. This finding is associated with an elevated glucose metabolism, leading to the detection of precursor lesions of pancreatic cancer in the FDG PET-CT scan. In addition, immunohistochemical staining of GLUT-2 was detectable in 45 (75%) of 60 human PanINs, whereas PanINs of grade 1B and higher showed a very extensive expression. Conclusions In conclusion, we demonstrate for the first time that an elevated glucose metabolism occurs already in precursor lesions of murine and human pancreatic carcinoma. These findings are the basis for the detection of precursor lesions by PET-CT, thereby helping improving the prognosis of this devastating disease.
Fendrich, Volker; Schneider, Ralph; Maitra, Anirban; Jacobsen, Ilse D; Opfermann, Thomas; Bartsch, Detlef K
Simultaneous EUS-FNA Diagnosis and TNM Staging of a Pancreatic Neuroendocrine Tumor in a Patient with an Unrecognized MEN Type 1
We report the case of a woman who, during oncological followup for bronchial carcinoid (diagnosed in 2005), papillary thyroid carcinoma, and bilateral parathyroid adenoma (simultaneously diagnosed in 2007), performed a pancreatic endoscopic ultrasonography with fine needle agobiopsy (EUS-FNA) for a positron emission tomography (PET) suspicion of pancreatic and hepatic lesions; during the procedure, the pancreatic and liver lesions were confirmed, and a peripancreatic lymph node involvement was found, allowing a complete pTNM staging during the same procedure.
Ferrara, Francesco; Luigiano, Carmelo; Maimone, Antonella; Bassi, Marco; Polifemo, Anna Maria; Baccarini, Paola; Cennamo, Vincenzo; Cremonini, Nadia; Fabbri, Carlo
Simultaneous EUS-FNA Diagnosis and TNM Staging of a Pancreatic Neuroendocrine Tumor in a Patient with an Unrecognized MEN Type 1.
We report the case of a woman who, during oncological followup for bronchial carcinoid (diagnosed in 2005), papillary thyroid carcinoma, and bilateral parathyroid adenoma (simultaneously diagnosed in 2007), performed a pancreatic endoscopic ultrasonography with fine needle agobiopsy (EUS-FNA) for a positron emission tomography (PET) suspicion of pancreatic and hepatic lesions; during the procedure, the pancreatic and liver lesions were confirmed, and a peripancreatic lymph node involvement was found, allowing a complete pTNM staging during the same procedure. PMID:23091757
Ferrara, Francesco; Luigiano, Carmelo; Maimone, Antonella; Bassi, Marco; Polifemo, Anna Maria; Baccarini, Paola; Cennamo, Vincenzo; Cremonini, Nadia; Fabbri, Carlo
Pancreatic tuberculosis with acquired immunodeficiency syndrome: A case report and systematic review
Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration.
Meesiri, Somchai
Pancreatic tuberculosis with acquired immunodeficiency syndrome: a case report and systematic review.
Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration. PMID:22363146
Meesiri, Somchai
Peptidomics-based Approach Reveals the Secretion of the 29Residue COOH- Terminal Fragment of the Putative Tumor Suppressor Protein DMBT1 from Pancreatic Adenocarcinoma Cell Lines1
Deleted in malignant brain tumors 1 is a putative tumor suppressor protein in brain, lung, esophageal, gastric, and colorectal cancer. Here we report the mass spectrometric identification of a 3335 Da peptide, which was found in serum-free conditioned medium from 5 of 15 pancreatic adenocarcinoma cell lines but not from 35 carcinoma cell lines and 2 nonmalignant pancreatic duct cell
Kazuki Sasaki; Kae Sato; Yasuto Akiyama; Kazuyoshi Yanagihara; Masaaki Oka; Ken Yamaguchi
Locally advanced anaplastic pancreatic adenocarcinoma with initial response to FOLFIRINOX and rapid progression after five months.
Anaplastic pancreatic carcinoma (APC) is a rare, aggressive variant of pancreatic ductal adenocarcinoma. Surgery is the preferred treatment whenever possible, however APC is often unresectable at presentation and prognosis remains poor. We present a case of APC which showed a marked initial response to FOLFIRINOX with decreased size and increased cystic change, however then rapidly progressed with innumerable hepatic metastases after five months of FOLFIRINOX treatment. Although there is limited data on use of FOLFIRINOX in locally advanced pancreatic adenocarcinoma, it remains an attractive option in comparison to radiotherapy and 5-fluorouracil. PMID:22487471
Shinagare, Atul B; Ramaiya, Nikhil H; Bellizzi, Andrew M; Mayer, Robert J
[Hypertriglyceridemia and acute pancreatitis].
Data of 26 patients suffering from severe pancreatitis, who were treated at the anesthesiologic intensive care unit during the years 1991 and 1992, were evaluated with respect to etiologic factors, especially hypertriglyceridemia, stage of the disease and clinical outcome. Hypertriglyceridemia was found in 13 cases (11 men, 2 women, mean age 42 +/- 9 years) with values between 330 mg/dl and 4000 mg/dl. Lipid electrophoresis revealed a pattern typical for type IV hyperlipidemia. Insulin dependent diabetes was present in 4 patients and 5 reported about an unusual high alcohol intake preceding pancreatitis. Beside surgical approaches, including drainage and lavage, and basic intensive care treatment plasmapheresis was performed in 8 patients with hypertriglyceridemia. 5 patients with pancreatitis and hypertriglyceridemia died out of multiorganic failure, and so the mortality rate was 38%. The group of patients with pancreatitis caused by cholelithiasis or chronic alcohol consumption showed a mortality rate of 46%. The poor outcome of pancreatitis associated with hypertriglyceridemia demonstrates the importance of the treatment of hypertriglyceridemia in order to prevent the development of pancreatitis. The determination of plasma triglyceride values should belong to the routine diagnostic procedures in acute pancreatitis. PMID:7709709
Lechleitner, M; Ladner, E; Seyr, M; Hoppichler, F; F�ger, B; Hackl, J M
Pleuropulmonary complications of pancreatitis
Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and�if long standing�may be complicated by a bronchopleural fistula. Images
Kaye, Michael D.
Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
Temsirolimus in Treating Patients With Metastatic or Locally Advanced Recurrent Endometrial Cancer
Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat.
Because diet has been shown to modulate the incidence of a wide variety of chemically induced cancers in experimental animals, various dietary constituents were evaluated for their ability to modulate the incidence of pancreatic exocrine cancer in male Wistar/Lewis rats given injections of the pancreatic carcinogen, azaserine. Ten different diet regimens were fed. The incidence of pancreatic cancers in rats fed a control diet was compared to that in groups fed diets formulated to evaluate the effect of caloric restriction, high protein, low protein, low fat, cyclopropenoid fatty acids, lipotrope deficiency, high unsaturated fat, and high saturated fat. The incidence of pancreatic adenomas and carcinomas was evaluated by light microscopy. The number of pancreatic neoplasms was reduced in carcinogen-treated groups which were underfed the control diet or fed the diet high in protein. Pancreatic carcinogenesis appeared to be enhanced in two groups which were fed diets containing 20% corn oil, i.e., high in unsaturated fat; whereas, the group fed a diet high in saturated fat had the same incidence of neoplasms as did the group fed the control diet. The pancreatic neoplasms from groups in which the incidence was enhanced by diet showed less evidence of acinar cell differentiation and displayed diverse histological types. In the lipotrope-deficient group, there was a significantly increased incidence of hepatocellular carcinoma; however, a low incidence of liver tumors was encountered in all other dietary groups. PMID:7459874
Roebuck, B D; Yager, J D; Longnecker, D S
Molecular Profiling of Pancreatic Adenocarcinoma and Chronic Pancreatitis Identifies Multiple Genes Differentially Regulated in Pancreatic Cancer 1
The molecular basis of pancreatic cancer is not understood. Previous attempts to determine the specific genes expressed in pancreatic cancer have been hampered by similarities between adenocarcinoma and chronic pancreatitis. In the current study, microarrays (Affymetrix) were used to profile gene expression in pancreatic adenocarcinoma (10), pancreatic cancer cell lines (7), chronic pancreatitis (5), and normal pancreas (5). Molecular profiling
Craig D. Logsdon; Diane M. Simeone; Charles Binkley; Thiruvengadam Arumugam; Joel K. Greenson; Thomas J. Giordano; David E. Misek; Samir Hanash
Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.
Bhatt, Alok; Menon, Aravind A; Bhat, Rama; Gurusiddana, Siddalingana Gouda Thaplar
Molecular Imaging of Late Somatostatin Receptor-Positive Metastases of Renal Cell Carcinoma in the Pancreas by 68Ga DOTATOC PET/CT: A Rare Differential Diagnosis to Multiple Primary Pancreatic Neuroendocrine Tumors.
Ga somatostatin receptor PET/CT, currently the most sensitive imaging modality for well-differentiated neuroendocrine tumors, is based on the molecular imaging of somatostatin receptors (SSTRs) that are expressed in different tumor entities such as neuroendocrine neoplasms, lymphomas, meningiomas, or renal cell cancer (RCC). Most neuroendocrine neoplasms show a high expression of SSTR subtypes 2A and 5, whereas the overexpression of SSTR2A in RCC is mainly seen in peritumoral vessels. Here we report a case with strongly SSTR-positive pancreatic lesions detected by Ga DOTATOC PET/CT, which histologically turned out to be ultralate metastases of a RCC. PMID:24561680
Peter, Luisa; S�nger, J�rg; Hommann, Merten; Baum, Richard Paul; Kaemmerer, Daniel
Measurement of duodenal tryptic activity and 75Se-selenomethionine pancreatic scanning compared as tests of pancreatic function
The results of a subjective assessment of pancreatic function, based on the appearance of a 75Se-pancreatic scan, were compared with measurements of the tryptic activity of duodenal aspirates in 16 normal and 38 abnormal subjects. In normals and in abnormals whose scans showed a generalized rather than a localized abnormality there was close agreement between the results of the two sets. In patients with a localized abnormality of the pancreatic head on scanning the tryptic activity of the aspirate was useful in differentiating carcinoma of the pancreas from that of the common bile duct. In general the scan was the more discriminative test though otherwise the places of the two tests in diagnosis are rather similar. The particular situations in which each test is valuable, or in which one or other test can be omitted, are discussed. ImagesFIG. 1
McCarthy, D. M.; Brown, Pamela
Animal models of pancreatic cancer for drug research.
Background: The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Objective: Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. Methods: The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. Conclusion: The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials. PMID:23489076
Kapischke, Matthias; Pries, Alexandra
Involvement of pancreatic and bile ducts in autoimmune pancreatitis
AIM: To examine the involvement of the pancreatic and bile ducts in patients with autoimmune pancreatitis. METHODS: Clinical and cholangiopancreatographic findings of 28 patients with autoimmune pancreatitis were evaluated. For the purposes of this study, the pancreatic duct system was divided into three portions: the ventral pancreatic duct; the head portion of the dorsal pancreatic duct; and the body and tail of the dorsal pancreatic duct. RESULTS: Both the ventral and dorsal pancreatic ducts were involved in 24 patients, while in 4 patients only the dorsal pancreatic duct was involved. Marked stricture of the bile duct was detected in 20 patients and their initial symptom was obstructive jaundice. Six patients showed moderate stenosis to 30%-40% of the normal diameter, and the other two patients showed no stenosis of the bile duct. Although marked stricture of the bile duct was detected in 83% (20/24) of patients who showed narrowing of both the ventral and dorsal pancreatic ducts, it was not observed in the 4 patients who showed involvement of the dorsal pancreatic duct alone (P?=?0.0034). CONCLUSION: Both the ventral and dorsal pancreatic and bile ducts are involved in patients with autoimmune pancreatitis.
Kamisawa, Terumi; Tu, Yuyang; Egawa, Naoto; Nakajima, Hitoshi; Tsuruta, Kouji; Okamoto, Atsutake
Pancreatic exocrine function testing
It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.
Goff, J.S.
Pancreatic Islet Transplantation
... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...
Management of necrotizing pancreatitis.
A comprehensive management plan is presented for patients with severe acute pancreatitis. These patients may have pancreatic or peripancreatic necrosis or pancreatic fluid collections. Multiple organ failure often develops in patients with severe pancreatitis. We therefore recommend that all patients with acute pancreatitis be evaluated for pancreatic anatomy and function. If a patient is seriously ill, a computed tomographic (CT) scan with vascular enhancement should be done. Meanwhile, vigorous fluid replacement is necessary using Swan-Ganz monitoring. Patients with necrosis do not need surgical intervention unless the clinical course or CT scan-guided aspiration shows infection. The objective of an operation should be to remove all infected tissue and fluid. A preoperative CT scan with vascular enhancement should be used as a guide during the operation to ensure that all foci of infected necrosis or fluid are eliminated. We have found that open packing and irrigation with sodium oxychlorosene are helpful in patients with extensive necrosis or those who become infected early after the onset of symptoms. In all, 40% to 50% of patients treated by closed drainage will require reoperation because of incomplete debridement. Persistent sepsis is an indication for reoperation. Images
Frey, C F
Autoantibodies in Autoimmune Pancreatitis
Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-?-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.
Smyk, Daniel S.; Rigopoulou, Eirini I.; Koutsoumpas, Andreas L.; Kriese, Stephen; Burroughs, Andrew K.; Bogdanos, Dimitrios P.
Sphincter of oddi (pancreatic) hypertension and recurrent pancreatitis
Major papilla pancreatic sphincter dysfunction, a variant of sphincter of Oddi dysfunction, causes pancreatitis and pancreatic-type\\u000a pain. The gold standard for diagnosis is sphincter of Oddi manometry, most commonly performed at endoscopic retrograde cholangiopancreatography\\u000a (ERCP). Noninvasive testing, such as secretin-stimulated transabdominal or endoscopic ultrasound assessment of pancreatic\\u000a duct diameter, is less reliable and has relatively low sensitivity. Two thirds of
Benedict M. Devereaux; Stuart Sherman; Glen A. Lehman
Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence
Pancreatic carcinogenesis in the Syrian hamster, induced by ..beta..-oxidized derivatives of N-nitroso-di-n-propylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of ductal adenomas and carcinomas. Acinar cells appear to undergo changes in differentiation, including pseudoductular transformation, giving rise to a new population of cells that resemble ductular or centroacinar types. This new population may then proliferate to form, first, cystic foci and subsequently cytadenomas and adenocarcinomas. Mucous metaplasia appears to develop at late stages of tumor development. Although the participation of ductular and centroacinar cells in pancreatic carcinogenesis cannot be excluded, very few tumors arise from the ductal epithelium. It is possible that some human pancreatic adenocarcinomas may also have their origin from dysplastic acinar cells, by analogy with the hamster model: focal acinar dyplasia being common in human pancreatic cancer patients. 90 references, 18 figures.
Flaks, B.
Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence.
Pancreatic carcinogenesis in the Syrian hamster, induced by beta-oxidized derivatives of N-nitroso-di-n-propylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of "ductal" adenomas and carcinomas. Acinar cells appear to undergo changes in differentiation, including pseudoductular transformation, giving rise to a new population of cells that resemble ductular or centroacinar types. This new population may then proliferate to form, first, cystic foci and subsequently cystadenomas and adenocarcinomas. Mucous metaplasia appears to develop at late stages of tumor development. Although the participation of ductular and centroacinar cells in pancreatic carcinogenesis cannot be excluded, very few tumors arise from the ductal epithelium. It is possible that some human pancreatic adenocarcinomas may also have their origin from dysplastic acinar cells, by analogy with the hamster model: focal acinar dysplasia being common in human pancreatic cancer patients. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. FIGURE 14. FIGURE 15. FIGURE 16. FIGURE 17. FIGURE 18.
Flaks, B
Environmental Risk Factors for Chronic Pancreatitis and Pancreatic Cancer
Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ?10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits
Claudia Nitsche; Peter Simon; F. Ulrich Weiss; Gabriele Fluhr; Eckhard Weber; Simone G�rtner; Claas O. Behn; Matthias Kraft; J�rg Ringel; Ali Aghdassi; Julia Mayerle; Markus M. Lerch
Gallstone pancreatitis: positive correlation between severe pancreatitis and passed stone
Background\\/Purpose. Little is known about whether the severity of pancreatitis depends upon persistent stone impaction or stone passage into the duodenum, and the role of endoscopic sphincterotomy (ES) has remained controversial. Methods. This study reviewed our experience of 183 patients with gallstone pancreatitis, with special attention paid to the relationship between the severity of pancreatitis, the severity of coexisting biliary
Masatoshi Isogai; Akihiro Yamaguchi; Tohru Harada; Yuji Kaneoka; Junji Washizu; Kiyoshi Aikawa
Genetics Home Reference: Hereditary pancreatitis
... to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with ... history of cancer. In affected individuals who develop pancreatic cancer, it is typically diagnosed in mid-adulthood. Complications ...
Pancreatic trauma: a concise review.
Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma. PMID:24379625
Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar
Loperamide-Induced Acute Pancreatitis
Acute pancreatitis is a common disease leading to hospitalizations, most often caused by gallstones or alcohol. We present a case of a patient diagnosed with acute pancreatitis considered to be due to loperamide treatment for diarrhea.
Vidarsdottir, Hanna; Moller, Pall Helgi; Bjornsson, Einar Stefan
Pancreatic trauma: A concise review
Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma.
Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar
Pancreatic Ductal and Acinar Cell Neoplasms in Carney Complex: A Possible New Association
Context: Carney complex (CNC) is a rare disease inherited as an autosomal dominant trait, associated with various tumors, and caused most frequently by inactivation of the PRKAR1A gene. Objectives: In our recent investigation of a large cohort of CNC patients, we identified several cases of pancreatic neoplasms. This possible association and PRKAR1A's possible involvement in pancreatic tumor have not been reported previously. Patients and Methods: Nine patients (2.5%) with CNC and pancreatic neoplasms in an international cohort of 354 CNC patients were identified; we studied six of them. Immunohistochemistry and PRKAR1A sequencing were obtained. Results: Three men and three women with a mean age of 49 yr (range 34�75 yr) had acinar cell carcinoma (n = 2), adenocarcinoma (n = 1), and intraductal pancreatic mucinous neoplasm (n = 3). Five patients had a germline PRKAR1A mutation, including two patients with acinar cell carcinoma, for whom mutations were found in a hemizygous state in the tumor, suggesting loss of heterozygosity. PRKAR1A expression was not detected in five of the six pancreatic neoplasms from CNC patients, whereas the protein was amply expressed on other sporadic pancreatic tumors and normal tissue. Conclusion: An unexpectedly high prevalence of rare pancreatic tumors was found among CNC patients. Immunohistochemistry and loss-of-heterozygosity studies suggest that PRKAR1A could function as a tumor suppressor gene in pancreatic tissue, at least in the context of CNC. Clinicians taking care of CNC patients should be aware of the possible association of CNC with a potentially aggressive pancreatic neoplasm.
Gaujoux, Sebastien; Tissier, Frederique; Ragazzon, Bruno; Rebours, Vinciane; Saloustros, Emmanouil; Perlemoine, Karine; Vincent-Dejean, Caroline; Meurette, Guillaume; Cassagnau, Elisabeth; Dousset, Bertrand; Bertagna, Xavier; Horvath, Anelia; Terris, Benoit; Carney, J. Aidan; Stratakis, Constantine A.
Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer
Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
Epigenetic targeting in pancreatic cancer.
The prognosis of pancreatic cancer patients is very poor, with a 5-year survival of less than 6%. Therefore, there is an urgent need for new therapeutic options in pancreatic cancer. In the past years it became evident that deregulation of epigenetic mechanisms plays an important role in pancreatic carcinogenesis. This review focuses on the exploitation of drugs that alter histone modifications, DNA methylation and microRNA expression as options for the treatment of pancreatic cancer. PMID:24433955
van Kampen, Jasmijn G M; Marijnissen-van Zanten, Monica A J; Simmer, Femke; van der Graaf, Winette T A; Ligtenberg, Marjolijn J L; Nagtegaal, Iris D
Molecular pathways in pancreatic carcinogenesis.
Pancreatic cancer is a genetic disease. Pancreatic cancers develop from one of three precursor lesions, pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs), and each arises in association with distinct genetic alterations. These alterations not only provide insight into the fundamental origins of pancreatic cancer but provide ample opportunity for improving early diagnosis and management of cystic precursors. PMID:22806689
Macgregor-Das, Anne M; Iacobuzio-Donahue, Christine A
Molecular Pathways in Pancreatic Carcinogenesis
Pancreatic cancer is a genetic disease. Pancreatic cancers develop from one of three precursor lesions, pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs), and each arises in association with distinct genetic alterations. These alterations not only provide insight into the fundamental origins of pancreatic cancer but provide ample opportunity for improving early diagnosis and management of cystic precursors.
Pathophysiology of autoimmune pancreatitis.
Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related disease. In addition, the pancreas of a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP. From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that the polymorphic genes encoding cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses. PMID:24891971
Pezzilli, Raffaele; Pagano, Nico
Pathophysiology of autoimmune pancreatitis
Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related disease. In addition, the pancreas of a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP. From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that the polymorphic genes encoding cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses.
Pezzilli, Raffaele; Pagano, Nico
Chronic pancreatitis: diagnosis and treatment.
Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism. Neurotensin is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic pancreatitis. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of chronic pancreatitis.
Sidhu, S.; Tandon, R. K.
Rational Therapy of Acute Pancreatitis
Management of acute pancreatitis represents a challenging aspect of everyday clinical practice that requires a multimodal and interdisciplinary approach. Mild cases of acute pancreatitis are usually self-limitating and treated with fluid resuscitation, analgesics, oxygen administration, and antiemetics. In addition to this, the role of nutritional support has been established for patients with severe acute pancreatitis with more evidence demonstrating its
D. �timac; G. Poropat
Gadolinium induced recurrent acute pancreatitis.
Acute pancreatitis is a sudden swelling and inflammation of the pancreas. The two most common causes are alcohol use and biliary stones. Drug-induced acute pancreatitis are rare (1.4-2%). In this present study, we present a case of recurrent acute pancreatitis induced by a specific magnetic-resonance-imaging (MRI) contrast agent called gadobenate dimeglumine. PMID:23395575
Blasco-Perrin, H; Glaser, B; Pienkowski, M; Peron, J M; Payen, J L
Adjuvant therapy for pancreatic cancer
Although the morbidity and mortality of pancreatic resection for cancer has been remarkably reduced during the last 20 years, there has been little change in long-term survival. Based on experience in the treatment of locally unresectable but nonmetastatic pancreatic cancer, adjuvant therapies have been devised that do have an impact on survival. The number of pancreatic resections remains low, however.
Harold O. Douglass
ERBB2 kinase domain mutation in the lung squamous cell carcinoma.
Mounting evidence exists that the activation of proto-oncogene by somatic mutation plays an important roles in the development of human cancers. Recent reports revealed that the kinase domain of ERBB2 gene, a proto-oncogene, is somatically mutated in the lung adenocarcinomas, suggesting the mutated ERBB2 gene may act as an oncogene in human cancers. The purpose of this was to see whether the ERBB2 kinase domain is mutated in other lung cancer types besides the adenocarcinoma. Here, we performed mutational analysis of the ERBB2 kinase domain by polymerase chain reaction-single strand conformation polymorphism assay in 114 non-adenocarcinoma type non-small cell lung cancers (NSCLCs) tissue samples, including 100 squamous cell carcinomas, three adenosquamous carcinomas and 11 large cell carcinomas. We detected the ERBB2 kinase domain mutation in one squamous cell carcinoma (1.0%). The detected ERBB2 mutation showed G to C transversion at bp 2305 (2305G>C), which would result in the substitution of Asp to His at codon 769 (D769H). The amino acid D769 is located in the alpha-helix within the kinase domain, which is important in the binding of ATP with ERBB2. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA and BRAF genes in the squamous cell carcinoma with the ERBB2 mutation, and found that the tumor did not harbor any EGFR or ERBB2 or K-RAS or PIK3CA or BRAF gene mutation, either. This study demonstrated that in addition to lung adenocarcinoma ERBB2 kinase domain mutation could occur in lung squamous cell carcinomas, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations may occasionally contribute to the development of lung squamous cell carcinomas. PMID:16029927
Lee, Jong Woo; Soung, Young Hwa; Kim, Su Young; Nam, Suk Woo; Park, Won Sang; Wang, Young Pil; Jo, Keon Hyun; Moon, Seok Whan; Song, Sang Yong; Lee, Jung Young; Yoo, Nam Jin; Lee, Sug Hyung
Angiopathies in pancreatic diabetes resulting from chronic pancreatitis
Summary��Conclusions. Marked diabetic micro- and macroangiopathies were recognized in three autopsy cases with pancreatic diabetes\\u000a resulting from chronic pancreatitis.\\u000a \\u000a \\u000a Background. Recent reports have suggested that diabetic retinopathy occurs as one of the microangiopathies in patients with secondary\\u000a diabetes following chronic pancreatitis.\\u000a \\u000a \\u000a \\u000a \\u000a Methods. We report three autopsy cases with pancreatic diabetes. Cases 1 and 2 showed alcoholic chronic pancreatitis. Case 3
Hideyuki Wakasugi; Yasuhiro Hara; Muneaki Abe; Yasaburo Katsuda
Genes and Proteins Differentially Expressed during In Vitro Malignant Transformation of Bovine Pancreatic Duct Cells1
Abstract Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an in vitro model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells formed intrapancreatic adenocarcinoma tumors on k-rasmut transfection after orthotopic injection in the nude mouse pancreas. Here we identified genes and proteins differentially expressed in the course of malignant transformation using reciprocal suppression subtractive hybridization and 2D gel electrophoresis and mass spectrometry, respectively. We identified 34 differentially expressed genes, expressed sequence tags, and 15 unique proteins. Differential expression was verified for some of the genes or proteins in samples from pancreatic carcinoma. Among these genes and proteins, the majority had already been described either to be influenced by a mutated ras or to be differentially expressed in pancreatic adenocarcinoma, thus proving the feasibility of our model. Other genes and proteins (e.g., BBC1, GLTSCR2, and rhoGDI?), up to now, have not been implicated in pancreatic tumor development. Thus, we were able to establish an in vitro model of pancreatic carcinogenesis, which enabled us to identify genes and proteins differentially expressed during the early steps of malignant transformation.
Jesnowski, R; Zubakov, Dmitri; Faissner, Ralf; Ringel, Jorg; Hoheisel, Jorg D; Losel, Ralf; Schnolzer, Martina; Lohr, Matthias
Genetic Instability in Pancreatic Cancer and Poorly Differentiated T^pe of Gastric Cancer1
To examine genetic instability during carcinogenesis, we screened 171 carcinomas of the breast, liver, proximal colon, stomach, pancreas, uterine cervix, and ovary for replication error at four microsatellite marker loci on chromosomes 2, 3, and 17. A significantly high incidence of genetic instability was observed in pancreatic (6 of 9 tumors) and gastric cancers (22 of 57 cases). In other
Hye-Jung Han; Akio Yanagisawa; Yo Kato; Jae-Gahb Park; Yusuke Nakamura
Splenic Abscess Caused by Streptococcus gallolyticus subsp. pasteurianus as Presentation of a Pancreatic Cancer
Splenic abscesses caused by Streptococcus bovis are rarely reported in the literature and are mainly seen in patients with endocarditis and associated colonic neoplasia/carcinoma. We report the first case of splenic abscess caused by Streptococcus gallolyticus subsp. pasteurianus (Streptococcus bovis biotype II/2) as presentation of a pancreatic cancer.
Su, Yanli; Miao, Bin; Wang, Hong; Wang, Chao
Resectable carcinoma developing in the remnant pancreas 7 years and 10 months after distal pancreatectomy for invasive ductal carcinoma of the pancreas: report of a case
Background Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is one of the most lethal and aggressive malignancies. Operative resection remains the only treatment providing prolonged survival, however, recurrence of pancreatic ductal adenocarcinoma occurs in up to 80% of patients with pancreatic cancer within 2�years of a potential curative resection. There are few reports of pancreatic carcinoma recurrence (primary second cancer) in the remnant pancreas after pancreatectomy. Case presentation A 52-year-old woman underwent a distal pancreatectomy for pancreatic cancer in September 2004. Adjuvant chemotherapy was started after surgery and continued for 4�years. In March 2012, marked elevation of DUPAN-II was observed, followed by an irregular stenotic finding in the main duct. We performed an en bloc resection of the remnant pancreas in July 2012. Histologically, the tumor contained a second primary pancreatic carcinoma with lymph node metastasis. At follow-up 20�months after the second operation, the patient was alive without recurrence. Fourteen cases of resectable cancer developing in the remnant pancreas after a pancreatectomy for cancer have been reported; a minority of these was identified as second primary tumors. Therefore, our patient�s primary second cancer is a rare event. Conclusion The patient is considered to have shown a rare, unique pancreatic cancer recurrence. Persistent elevation of a tumor marker and extensive imaging led to proper diagnosis and treatment.
New cell lines of gastric and pancreatic cancer: distinct morphology, growth characteristics, expression of epithelial and immunoregulatory antigens
Two new cell lines from stomach cancers and one from a pancreatic carcinoma are presented. MZ-GC-1 was established from a hepatic metastasis of a well differentiated gastric adenocarcinoma. MZ-GC-2 was derived from ascites induced by a poorly differentiated gastric adenocarcinoma. MZ-PC-1 originated from the pleural effusion of a moderately well differentiated pancreatic ductal adenocarcinoma. MZ-GC-1 cells were adherent and partially
M. Heike; K. H. Meyer zum B�schenfelde; W. G. Dippold; O. R�hrig; R. Moll; H. E. Gabbert; A. Knuth
Pancreatitis activates pancreatic apelin-APJ axis in mice
Pancreatitis is classified into acute pancreatitis (AP) and chronic pancreatitis (CP). Apelin, a small regulatory peptide, is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed in the pancreas. The aims of this study were to examine whether apelin influences the inflammatory and fibrosis responses to pancreatitis in mice and to identify mechanisms behind apelin's activities. Supramaximal cerulein induction of AP or CP caused significant (P < 0.05) elevations in pancreatic apelin and APJ expression. Levels declined during the recovery phases. In apelin gene-knockout mice with pancreatitis, pancreatic neutrophil invasion and myeloperoxidase activity were enhanced significantly, and apelin treatment suppressed both. Apelin exposure reduced CP-induced elevations of extracellular matrix-associated proteins. Apelin inhibited PDGF-simulated connective tissue growth factor production and proliferation of pancreatic stellate cells (PSCs). Serum granulocyte colony-stimulating factor and keratinocyte cytokine levels were higher in apelin gene-knockout than wild-type mice with pancreatitis. Apelin reduced AP- and CP-induced elevations in pancreatic NF-?B activation. Together, these findings imply that the pancreatic apelin-APJ system functions to curb the inflammatory and fibrosis responses during pancreatitis. Furthermore, findings suggest that apelin reduces inflammation and fibrosis by reducing neutrophil recruitment and PSC activity. Inhibition of neutrophil invasion may be mediated by reduced keratinocyte cytokine and granulocyte colony-stimulating factor secretion. Apelin-induced reductions in PSC proliferation and connective tissue growth factor production are putative mechanisms underlying apelin's inhibition of extracellular matrix production. The apelin-associated changes in NF-?B binding may be linked to apelin's regulation of pancreatic inflammatory and fibrosis responses during pancreatitis.
Han, Song; Englander, Ella W.; Gomez, Guillermo A.; Aronson, Judith F.; Rastellini, Cristiana; Garofalo, R. P.; Kolli, Deepthi; Quertermous, Thomas; Kundu, Ramendra
Metastases of esophageal carcinoma to skeletal muscle: Single center experience
Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma.
Cincibuch, Jan; Myslivecek, Miroslav; Melichar, Bohuslav; Neoral, Cestmir; Metelkova, Iva; Zezulova, Michaela; Prochazkova-Studentova, Hana; Flodr, Patrik; Zlevorova, Miloslava; Aujesky, Rene; Cwiertka, Karel
Endotherapy in chronic pancreatitis
Chronic pancreatitis (CP) is a progressive disease with irreversible changes in the pancreas. Patients commonly present with pain and with exocrine or endocrine insufficiency. All therapeutic efforts in CP are directed towards relief of pain as well as the management of associated complications. Endoscopic therapy offers many advantages in patients with CP who present with ductal calculi, strictures, ductal leaks, pseudocyst or associated biliary strictures. Endotherapy offers a high rate of success with low morbidity in properly selected patients. The procedure can be repeated and failed endotherapy is not a hindrance to subsequent surgery. Endoscopic pancreatic sphincterotomy is helpful in patients with CP with minimal ductal changes while minor papilla sphincterotomy provides relief in patients with pancreas divisum and chronic pancreatitis. Extracorporeal shock wave lithotripsy is the standard of care in patients with large pancreatic ductal calculi. Long term follow up has shown pain relief in over 60% of patients. A transpapillary stent placed across the disruption provides relief in over 90% of patients with ductal leaks. Pancreatic ductal strictures are managed by single large bore stents. Multiple stents are placed for refractory strictures. CP associated benign biliary strictures (BBS) are best treated with multiple plastic stents, as the response to a single plastic stent is poor. Covered self expanding metal stents are increasingly being used in the management of BBS though further long term studies are needed. Pseudocysts are best drained endoscopically with a success rate of 80%-95% at most centers. Endosonography (EUS) has added to the therapeutic armamentarium in the management of patients with CP. Drainage of pseudcysts, cannulation of inaccessible pancreatic ducts and celiac ganglion block in patients with intractable pain are all performed using EUS. Endotherapy should be offered as the first line of therapy in properly selected patients with CP who have failed to respond to medical therapy and require intervention.
Tandan, Manu; Reddy, D Nageshwar
Comparative Characterization of Stroma Cells and Ductal Epithelium in Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive stroma being also present in chronic pancreatitis (CP). Using immunohistochemistry, the stroma of CP and PDAC was comprehensively analyzed and correlated with epithelial/carcinoma-related alterations and clinicopathological patient characteristics. While there were no significant differences between CP and PDAC regarding the distribution of CD3+ T cells and ?-SMA+ fibroblasts, proportions of CD4+ and CD8+ T cells were significantly lower and numbers of CD25+(CD4+) and FoxP3+(CD4+) regulatory T cells were greater in PDAC compared with CP. Macrophages were more prevalent in CP, but localized more closely to carcinoma cells in PDAC, as were ??-T cells. Duct-related FoxP3 and L1CAM expression increased from CP to PDAC, while vimentin expression was similarly abundant in both diseases. Moreover, stromal and epithelial compartments of well-differentiated tumors and CPs shared considerable similarities, while moderately and poorly differentiated tumors significantly differed from CP tissues. Analysis of 27 parameters within each pancreatic disease revealed a significant correlation of i) CD4+ and FoxP3+CD4+ T cells with FoxP3 expression in PDAC cells, ii) ?-SMA+ fibroblasts with L1CAM expression and proliferation in PDAC cells, iii) CD3 and CD8 expression with ??-TCR expression in both pancreatic diseases and iv) CD68+ and CD163+ macrophages with vimentin expression in PDAC cells. High expression of FoxP3, vimentin and L1CAM in PDAC cells as well as a tumor-related localization of macrophages each tended to correlate with higher tumor grade. Multivariate survival analysis revealed a younger age at time of surgery as a positive prognostic marker for PDAC patients with the most frequently operated disease stage T3N1M0. Overall this study identified several interrelationships between stroma and epithelial/carcinoma cells in PDACs but also in CP, which in light of previous experimental data strongly support the view that the inflammatory stroma contributes to malignancy-associated alterations already in precursor cells during CP.
Helm, Ole; Mennrich, Ruben; Petrick, Domantas; Goebel, Lisa; Freitag-Wolf, Sandra; Roder, Christian; Kalthoff, Holger; Rocken, Christoph; Sipos, Bence; Kabelitz, Dieter; Schafer, Heiner; Oberg, Hans-Heinrich; Wesch, Daniela; Sebens, Susanne
Treatment of pain in chronic pancreatitis by inhibition of pancreatic secretion with octreotide
It has been suggested that pancreatic ductal hypertension, secondary to pancreatic outflow obstruction, is a cause of pain in chronic pancreatitis. This study investigated the effect of inhibiting pancreatic secretion with octreotide in chronic pancreatitis pain. Ten patients with chronic alcoholic pancreatitis and severe daily pain were included in an intraindividual double blind crossover study. All patients received octreotide (3
P Malfertheiner; D Mayer; M B�chler; J E Dom�nguez-Mu�oz; B Schiefer; H Ditschuneit
Solitary Main Pancreatic Ductal Calculus of Possible Biliary Origin Causing Acute Pancreatitis
Context Pancreatic ductal calculi are most often associated with chronic pancreatitis. Radiological features of chronic pancreatitis are readily evident in the presence of these calculi. However, acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. Case report A 59 -year-old man presented with a first episode of acute pancreatitis. Contrast enhanced computerized tomography (CT)
Ramakrishna Prasad; Chowdary Chaparala; Rafiuddin Patel; James Ahsley Guthrie; Mervyn Huw Davies; Pierre J Guillou; Krishna V Menon
Primary Pancreatic Leiomyosarcoma
Primary pancreatic leiomyosarcomas are rare malignant neoplasms with an aggressive course and a large size. A 56-year-old woman presented with an 8-year history of abdominal pain. Multislice computed tomography revealed a large heterogeneous mass with necrotic, calcified and macroscopic fatty areas. The tumor was excised. Histopathological evaluation revealed leiomyosarcoma of the pancreas. If a patient has a large size mass with a cystic-necrotic component, pancreatic leiomyosarcoma should be considered in the differential diagnosis list after excluding other common differential diagnoses.
Kocakoc, Ercan; Havan, Nuri; Bilgin, Mehmet; Atay, Musa
Analysis of the Lewisx epitope in human pancreas and pancreatic adenocarcinomas.
The Lewisx epitope (Gal beta 1-4[Fuc alpha 1-3]GlcNAc-R) can be detected in most ductal pancreatic carcinomas. However, few data pertain to its expression in normal exocrine pancreas and its biochemistry. We compared the expression of the Lewisx epitope in normal pancreas with its expression in pancreatic adenocarcinomas and tumor cell lines and to further characterize the nature of the antigens bearing this epitope with immunochemical methods. On frozen tissue sections of normal pancreas, the Lewisx epitope was detected focally in acinar cell granules; sialosyl-Lewisx was detected in centroacinar cells and the cytoplasm of intralobular ducts. Sixteen of 19 pancreatic carcinomas expressed the Lewisx antigen on tissue sections; however, there was no correlation with prognostic parameters, such as tumor grade or stage. Eighteen of 19 tumor specimens were positive for sialosyl-Lewisx. Analysis of pancreatic carcinoma cell lines (CAPAN-1, CAPAN-2, and DAN-G) revealed intracytoplasmic expression of sialosyl-Lewisx epitopes in these cells, and cell surface reactivity was detected on flow cytometry for sialosyl-Lewisx. Lectin-affinity chromatography of cytoplasmac preparations showed that Lewisx-positive antigens of normal human pancreas bind to SBA and UEA-I lectins but have little or no affinity to WGA, GS-I, or DBA lectins, indicating the presence of Fuc and Gal oligosaccharide residues. It was concluded that the Lewisx and sialosyl-Lewisx antigens are nonpolymorphic carbohydrate determinants that are present in secretory granules of acinar cells, ductules, and pancreatic secretions. This makes the Lewisx antigen suitable for the analysis of the secretory process in the exocrine pancreas and the study of secretory differentiation antigens in ductal pancreatic carcinoma. PMID:1376758
Sinn, H P; Brown, S A; Oberle, E; Thompson, J S
Is acute recurrent pancreatitis a chronic disease?
Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis
Alberto Mariani; Pier Alberto Testoni
Endoscopic management of acute biliary pancreatitis.
Acute pancreatitis represents numerous unique challenges to the practicing digestive disease specialist. Clinical presentations of acute pancreatitis vary from trivial pain to severe acute illness with a significant risk of death. Urgent endoscopic treatment of acute pancreatitis is considered when there is causal evidence of biliary pancreatitis. This article focuses on the diagnosis and endoscopic treatment of acute biliary pancreatitis. PMID:24079788
Kuo, Vincent C; Tarnasky, Paul R
Obstructive jaundice due to von Hippel-Lindau disease-associated pancreatic lesions: A case report
von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited neoplastic syndrome that may lead to pancreatic masses and obstructive jaundice. The present study describes the case of a 20-year-old male who suffered from obstructive jaundice due to VHL disease-associated pancreatic lesions whose primary symptom was dizziness, followed by the appearance of jaundice. Since the excision of the renal cell carcinomas was not possible, the patient also refused surgery to resect the pancreatic head mass. A metallic stent was placed at the stenosis site of the common bile duct. Percutaneous transhepatic cholangiography (PTCD) surgery was later performed following complete blockage of the stent, however, to date, the patient continues to rely on PTCD. VHL disease-associated pancreatic lesions are rarely the direct cause of mortality, however, obstructive jaundice due to these lesions may be lethal. Therefore, the treatment of patients with incurable renal or central nervous system tumors and obstructive jaundice presents a problem.
Precursor Lesions for Sporadic Pancreatic Cancer: PanIN, IPMN, and MCN
Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.
Distler, M.; Aust, D.; Weitz, J.; Pilarsky, C.; Grutzmann, Robert
Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer.
Pancreatic cancer is an aggressive, frequently fatal malignancy that strikes 37,000 patients annually in the U.S.A. It is poorly responsive to standard chemotherapies such as gemcitabine. Approximately 5-10% of pancreatic cancer occurs in the setting of a BRCA2 mutation. Breast and ovarian carcinomas that harbor BRCA2 mutations are susceptible to the effects of an emerging class of targeted agents, namely, poly(ADP-ribose) polymerase (PARP) inhibitors. This report describes the case of a patient with a germline BRCA2 mutation and an associated pancreatic cancer treated with iniparib (BSI-201), a PARP inhibitor, who demonstrated a complete pathologic response to this agent. This case highlights the potential benefit for PARP inhibition in BRCA2-related pancreatic cancer. PMID:21508395
Fogelman, David R; Wolff, Robert A; Kopetz, Scott; Javle, Milind; Bradley, Charles; Mok, Isabel; Cabanillas, Fernando; Abbruzzese, James L
Exocrine pancreatic neoplasms in the mummichog (fundulus heteroclitus) from a creosote-contaminated site
A high prevalence of exocrine pancreatic neoplasms occurred in mummichog, Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River, Virginia. A total of 20 neoplasms occurred in a group of about 1100 fish evaluated histologically. Of 240 adult fish collected during October 1991, 3.3% had pancreatic neoplasms. Adjusted total lesion prevalence for fish belonging to size classes III and IV was 6.7%. Pancreatic neoplasms were not observed in 234 fish collected at this site during May 1991, nor were pancreatic tumors found in 420 fish examined from 7 other localities. Lesions involved both mesenteric and intrahepatic exocrine pancreas and ranged from well-differentiated acinar cell adenomas to poorly differentiated acinar cell carcinomas.
Fournie, J.W.; Vogelbein, W.K.
Squamous cell carcinoma of the pancreas.
Squamous cell carcinoma (SCC) of the pancreas is a controversial entity of uncertain origin, as the pancreas is entirely devoid of squamous cells. Cases of pancreatic carcinomas that exhibit primary squamous morphology are rarely described in the literature. We report a case of primary SCC of the pancreas in a 66-year-old woman with complaints of epigastric pain of five months duration. Imaging studies demonstrated a solid tumor in the body of the pancreas that invaded the superior mesenteric (SMA) and celiac arteries, as well as regional lymph nodes. Cytological examination of an endosonography-guided fine needle aspiration (EUS-FNA) specimen confirmed the diagnosis of well-differentiated SCC of the pancreas. On the basis of diagnosis and examinations prior to chemotherapy, we did not detect any SCC lesions that might have metastasized to the pancreas. Primary SCC of the pancreas is a rare entity that comprises 0.05% of all exocrine pancreatic carcinomas. The clinical profile and biological behavior of pancreas SCC are similar to typical pancreatic ductal adenocarcinomas. PMID:23725072
Nikfam, Sepideh; Sotoudehmanesh, Rasoul; Pourshams, Akram; Sadeghipour, Alireza; Sotoudeh, Masoud; Mohamadnejad, Mehdi
HPC2 1-B3: A Novel Monoclonal Antibody to Screen for Pancreatic Ductal Dysplasia
Background Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. Our objective was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. Methods Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (n=23), IPMN grade 1 (n=16), grade 2 (n=9), grade 3 (n=13), and various grades of adenocarcinoma (n=17). One monoclonal antibody, HPC2 1-B3, was isolated that specifically immunostained adenocarcinoma and all grades of IPMN. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical followup. Results HPC2 1-B3 was negative in all of the chronic pancreatitis cases tested (0/31). In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all well to moderately differentiated pancreatic ductal adenocarcinomas (16/16). It showed only weak focal staining of poorly differentiated carcinoma. All high grade IPMNs were positive for HPC2 1-B3. Most low to intermediate grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 showed the relative risk (2.0 [1.23�3.26]) for detecting at least low-grade dysplasia was statistically significant (Fisher Exact test p-value=0.002). Conclusions In order to reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. Our data indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia.
Morgan, Terry K.; Hardiman, Karin; Corless, Christopher L.; White, Sandra L.; Bonnah, Robert; Van de Vrugt, Henry; Sheppard, Brett C.; Grompe, Markus; Cosar, Ediz F.; Streeter, Philip R.
Histological subtypes of oral non-tonsillar squamous cell carcinoma in dogs.
Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location. PMID:22300705
Nemec, A; Murphy, B; Kass, P H; Verstraete, F J M
... and treatments A - D Basal cell carcinoma Basal cell carcinoma Basal cell carcinoma: This skin cancer often ... skin tissue and bone. Learn more about basal cell carcinoma: Basal cell carcinoma: Signs and symptoms Basal ...
... and treatments Q - T Squamous cell carcinoma Squamous cell carcinoma Squamous cell carcinoma : This man's skin has ... SCC is highly curable. Learn more about squamous cell carcinoma: Squamous cell carcinoma: Signs and symptoms Squamous ...
Cystic dystrophy of the duodenal wall is not always associated with chronic pancreatitis
Cystic dystrophy of the duodenal wall is a rare form of the disease which was described in 1970 by French authors who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of the duodenum and the head of the pancreas. German authors have defined this area as a �groove�. We report our recent experience on cystic dystrophy of the paraduodenal space and systematically review the data in the literature regarding the alterations of this space. A MEDLINE search of papers published between 1966 and 2010 was carried out and 59 papers were considered for the present study; there were 19 cohort studies and 40 case reports. The majority of patients having groove pancreatitis were middle aged. Mean age was significantly higher in patients having groove carcinoma. The diagnosis of cystic dystrophy of the duodenal wall can now be assessed by multidetector computer tomography, magnetic resonance imaging and endoscopic ultrasonography. These latter two techniques may also add more information on the involvement of the remaining pancreatic gland not involved by the duodenal malformation and they may help in differentiating �groove pancreatitis� from �groove adenocarcinoma�. In conclusion, chronic pancreatitis involving the entire pancreatic gland was present in half of the patients with cystic dystrophy of the duodenal wall and, in the majority of them, the pancreatitis had calcifications.
Pezzilli, Raffaele; Santini, Donatella; Calculli, Lucia; Casadei, Riccardo; Morselli-Labate, Antonio Maria; Imbrogno, Andrea; Fabbri, Dario; Taffurelli, Giovanni; Ricci, Claudio; Corinaldesi, Roberto
Upregulation of Wnt5a promotes epithelial-to-mesenchymal transition and metastasis of pancreatic cancer cells
Background Pancreatic cancer is one of the most lethal cancers worldwide. The aim of this study was to determine the expression pattern, clinical significance, and biological functions of Wnt5a in pancreatic cancer. Methods Immunohistochemistry was performed to examine Wnt5a expression in 134 surgically resected pancreatic adenocarcinoma and adjacent normal pancreatic tissues. Associations of Wnt5a expression with clinicopathological factors and cancer-specific survival were analyzed. The effects of Wnt5a overexpression or silencing on the invasiveness and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells were studied. Silencing of ?-catenin by small interfering RNA was done to determine its role in the Wnt5a-mediated tumor phenotype. Results The percentage of Wnt5a positive expression showed a bell-shaped pattern in pancreatic cancer tissues, peaking in well-differentiated carcinomas. The median cancer-specific survival was comparable between patients with positive versus negative expression of Wnt5a. Overexpression of Wnt5a promoted the migration and invasion of pancreatic cancer cells, whereas Wnt5a depletion had an inhibitory effect. In an orthotopic pancreatic cancer mouse model, Wnt5a overexpression resulted in increased invasiveness and metastasis, coupled with induction of EMT in tumor cells. Treatment with recombinant Wnt5a elevated the nuclear ?-catenin level in pancreatic cancer cells, without altering the Ror2 expression. Targeted reduction of ?-catenin antagonized exogenous Wnt5a-induced EMT and invasiveness in pancreatic cancer cells. Conclusion Upregulation of Wnt5a promotes EMT and metastasis in pancreatic cancer models, which involves activation of ?-catenin-dependent canonical Wnt signaling. These findings warrant further investigation of the clinical relevance of Wnt5 upregulation in pancreatic cancer.
Hepatobiliary and pancreatic ascariasis.
Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. The majority of infections occur in the developing countries of Asia and Latin America. Of 4 million people infected in the United States, a large percentage are immigrants from developing countries. Ascaris-related clinical disease is restricted to subjects with heavy worm load, and an estimated 1.2 to 2 million such cases, with 20,000 deaths, occur in endemic areas per year. More often, recurring moderate infections cause stunting of linear growth, cause reduced cognitive function, and contribute to existing malnutrition in children in endemic areas. HPA is a frequent cause of biliary and pancreatic disease in endemic areas. It occurs in adult women and can cause biliary colic, acute cholecystitis, acute cholangitis, acute pancreatitis, and hepatic abscess. RPC causing hepatic duct calculi is possibly an aftermath of recurrent biliary invasion in such areas. Ultrasonography can detect worms in the biliary tract and pancreas and is a useful noninvasive technique for diagnosis and follow-up of such patients. ERCP can help diagnose biliary and pancreatic ascariasis, including ascaris in the duodenum. Also, ERCP can be used to extract worms from the biliary and pancreatic ducts when indicated. Pyrantel pamoate, mebendazole, albendazole and levamisole are effective drugs and can be used for mass therapy to control ascariasis in endemic areas. PMID:11293175
Khuroo, M S
Population-Based Stomach Cancer Registry
Primary Stomach Carcinoma:; Adenocarcinoma; Papillary Adenocarcinoma; Tubular Adenocarcinoma; Mucinous Adenocarcinoma; Signet-ring Cell Carcinoma; Adenosquamous Carcinoma; Squamous Cell Carcinoma; Small Cell Carcinoma; Undifferentiated Carcinoma; Other (Specify); Or Primary:; Esophagogastric Junction Carcinoma; Neuroendocrine Tumors; GiST; LNH
Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer
Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma
Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis
Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancr