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Chemoprevention of Esophageal Adenocarcinoma
The incidence of esophageal adenocarcinoma (EAC) is rising rapidly in Western countries, and effective chemoprevention for this malignancy is lacking. Endoscopic surveillance of patients with Barrett's esophagus is currently employed to diagnose EAC at earlier stages, but this strategy has several limitations. Non-steroidal anti-inflammatory drugs and proton pump inhibitors are the most promising agents for prevention of EAC, and a randomized controlled trial of aspirin and esomeprazole is ongoing. Other agents under investigation include green tea, berries, and antioxidants. Cost-effectiveness analyses have shown that chemopreventive agents need to be highly effective at preventing EAC in order to have benefit beyond endoscopic surveillance.
Dietary Supplement Use and Risk of Neoplastic Progression in Esophageal Adenocarcinoma: A Prospective Study
The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339
Linda M. Dong; Alan R. Kristal; Ulrike Peters; Jeannette M. Schenk; Carissa A. Sanchez; Peter S. Rabinovitch; Patricia L. Blount; Robert D. Odze; Kamran Ayub; Brian J. Reid; Thomas L. Vaughan
Recent developments in esophageal adenocarcinoma.
Answer questions and earn CME/CNE Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. PMID:23818335
Lagergren, Jesper; Lagergren, Pernilla
FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer
Strategies to improve outcomes in esophageal adenocarcinoma.
Esophageal adenocarcinoma is one of the fastest rising cancers in Western society. Incidence has increased by 600% within the last 30 years. Rates of diagnosis and death run parallel due to the poor prognosis and a lack of effective treatments. Potentially curative treatments are followed by high rates of disease recurrence. For the majority of patients, who present with advanced disease, we have no effective treatment. We discuss the key areas of progress in this demanding field and offer our views on the direction of future research and treatment. PMID:24621143
Cowie, Andrew; Noble, Fergus; Underwood, Timothy
Epidermal growth factor receptor expression in esophageal adenocarcinoma: relationship with tumor stage and survival after esophagectomy.
Background and Aims. Esophageal adenocarcinoma (EA) is an aggressive tumor with increasing incidence in occidental countries. Several prognostic biomarkers have been proposed, including epidermal growth factor receptor (EGFR). The aim of this study was to assess whether EGFR expression predicts EA staging and patient survival. Methods. In this historical cohort, consecutive patients with EA managed between 2000 and 2010 were considered eligible for the study. Surgical specimens of patients treated with transhiatal esophagectomy were evaluated to establish EGFR expression and tumor differentiation. Staging was classified according with tumor-node-metastasis (TNM) system. Survival was determined according to either medical register or patient's family contact. Results. Thirty-seven patients who underwent esophagectomy without presurgical chemotherapy or radiotherapy were studied. EGFR expression was found in 16 patients (43%). EGFR expression was more frequent as higher was the TNM (I and II = 0% versus III = 47% versus IV = 100%; P < 0.001). Average survival in months was significantly shorter in the group of patients with EGFR expression (10.5 versus 21.7; P = 0.001). Conclusions. In patients with esophageal adenocarcinoma treated with transhiatal esophagectomy, EGFR expression was related to higher TNM staging and shorter survival. EGFR expression might be assumed as a prognostic marker for esophageal adenocarcinoma. PMID:22792097
Navarini, Daniel; Gurski, Richard R; Madalosso, Carlos Augusto; Aita, Lucas; Meurer, Luise; Fornari, Fernando
Epidermal Growth Factor Receptor Expression in Esophageal Adenocarcinoma: Relationship with Tumor Stage and Survival after Esophagectomy
Background and Aims. Esophageal adenocarcinoma (EA) is an aggressive tumor with increasing incidence in occidental countries. Several prognostic biomarkers have been proposed, including epidermal growth factor receptor (EGFR). The aim of this study was to assess whether EGFR expression predicts EA staging and patient survival. Methods. In this historical cohort, consecutive patients with EA managed between 2000 and 2010 were considered eligible for the study. Surgical specimens of patients treated with transhiatal esophagectomy were evaluated to establish EGFR expression and tumor differentiation. Staging was classified according with tumor-node-metastasis (TNM) system. Survival was determined according to either medical register or patient's family contact. Results. Thirty-seven patients who underwent esophagectomy without presurgical chemotherapy or radiotherapy were studied. EGFR expression was found in 16 patients (43%). EGFR expression was more frequent as higher was the TNM (I and II = 0% versus III = 47% versus IV = 100%; P < 0.001). Average survival in months was significantly shorter in the group of patients with EGFR expression (10.5 versus 21.7; P = 0.001). Conclusions. In patients with esophageal adenocarcinoma treated with transhiatal esophagectomy, EGFR expression was related to higher TNM staging and shorter survival. EGFR expression might be assumed as a prognostic marker for esophageal adenocarcinoma.
Navarini, Daniel; Gurski, Richard R.; Madalosso, Carlos Augusto; Aita, Lucas; Meurer, Luise; Fornari, Fernando
Gastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinoma
Background MicroRNAs (miRNAs) play critical roles in tumor development and progression. The fact that a single miRNA can regulate hundreds of genes places miRNAs at critical hubs of signaling pathways. In this study, we investigated the miRNA expression profile in gastric adenocarcinomas and compared it to esophageal adenocarcinomas to better identify a unique miRNA signature of gastric adenocarcinoma. Methods and Results The miRNA expression profile was obtained using Agilent and Exiqon microarray platforms on primary gastric adenocarcinoma tissue samples. The cross comparison of results identified 17 up-regulated and 12 down-regulated miRNAs that overlapped in both platforms. Quantitative real-time RT-PCR was performed for independent validation of a representative set of 8 miRNAs in gastric and esophageal adenocarcinomas as compared to normal gastric mucosa or esophageal mucosa, respectively. The de-regulation of miR-146b-5p, -375, -148a, -31, and -451 was significantly associated with gastric adenocarcinomas. On the other hand, de-regulation of miR-21 (up-regulation) and miR-133b (down-regulation) was detectable in both gastric and esophageal adenocarcinomas. Interestingly, miR-200a was significantly down-regulated in gastric adenocarcinoma (p=0.04) but up-regulated in esophageal adenocarcinoma samples (p=0.001). In addition, the expression level of miR-146b-5p displayed a strong correlation with the tumor staging of gastric cancer. Conclusion Gastric adenocarcinoma displays a unique miRNA signature that distinguishes it from esophageal adenocarcinoma. This specific signature could reflect differences in the etiology and/or molecular signaling in these two closely related cancers. Our findings suggest important miRNA candidates that can be investigated for their molecular functions and possible diagnostic, prognostic, and therapeutic role in gastric adenocarcinoma.
Chen, Zheng; Saad, Rama; Jia, Peilin; Peng, DunFa; Zhu, Shoumin; Washington, M. Kay; Zhao, Zhongming; Xu, Zekuan; El-Rifai, Wael
AXL mediates TRAIL resistance in esophageal adenocarcinoma.
The overexpression of AXL receptor tyrosine kinase is a frequent finding that has been associated with poor prognosis in esophageal adenocarcinoma (EAC). As the majority of EAC are intrinsically resistant to DNA-damaging therapies, an alternative therapeutic approach based on the activation of death receptors may be warranted. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been evaluated in clinical trials and found promising as anticancer agent with mild side effects; unfortunately, resistance to TRAIL remains a major clinical problem. Herein, we explored the role of AXL in TRAIL resistance and elucidated the underlying mechanism. Overexpression of AXL in OE33 and OE19 cells promoted cell survival and attenuated TRAIL-induced cellular and molecular markers of apoptosis. In contrast, knockdown of endogenous AXL sensitized FLO-1 cells to TRAIL. The mechanism by which AXL regulates TRAIL resistance was examined. Protein and mRNA expression of DR4 and DR5 death receptors was not downregulated by AXL. In addition, the possible involvement of FLICE-inhibitory protein (FLIP) in regulating the interaction of caspase-8 with Fas-associated death domain protein (FADD) was excluded, as AXL did not enhance FLIP expression or FLIP/FADD association. Alternatively, protein association of AXL with DR5, independent of TRAIL, was confirmed, suggesting that AXL could regulate DR5 receptor activity. The AXL/DR5 association had no negative effect on TRAIL-induced interaction with FADD. However, the AXL/DR5 interaction blocked the recruitment of caspase-8 to the death-inducing signal complex (DISC). Collectively, our findings uncover a novel mechanism of TRAIL resistance mediated by AXL through regulation of the DISC and provide strong evidence that AXL could be exploited as a therapeutic target to circumvent TRAIL resistance. PMID:23479507
Hong, Jun; Belkhiri, Abbes
Barrett�s and Esophageal Adenocarcinoma Consortium (BEACON)
An international consortium with epidemiologic studies of esophageal adenocarcinoma and Barrett's esophagus. Analyses so far have included reproductive factors, cigarette smoking, alcohol consumption, non-steroidal anti-inflammatory drugs, excess risk models, anthropometry, and genome-wide analyses for susceptibility loci.
Duodenal reflux produces hyperproliferative epithelial esophagitis�A possible precursor to esophageal adenocarcinoma in the rat
Esophageal reflux of duodenal contents converts a rat nitrosamine esophageal cancer model from squamous cell carcinoma to\\u000a adenocarcinoma. Further, there was a tendency for male rats to have a higher incidence of cancer than female rats. However,\\u000a chemical castration with the gonadotropin-releasing hormone analog leuprolide did not protect male or female animals from\\u000a developing cancer. We have identified an early
Colman K. Byrnes; Anil Bahadursingh; Nabeel Akhter; Narasimham L. Parinandi; Viswanathan Natarajan; Elizabeth Montgomery; Tarik Tihan; Mark D. Duncan; Petra H. Nass; John W. Harmon
Esophageal Adenocarcinoma: Treatment Modalities in the Era of Targeted Therapy
Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at an alarming\\u000a rate. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence\\u000a and metastasis. Multiple molecular pathways including the epidermal growth factor receptor, vascular endothelial growth factor,\\u000a v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinase
Kaushik Mukherjee; A. Bapsi Chakravarthy; Laura W. Goff; Wael El-Rifai
NSAIDs Modulate CDKN2A, TP53, and DNA Content Risk for Progression to Esophageal Adenocarcinoma
Background Somatic genetic CDKN2A, TP53, and DNA content abnormalities are common in many human cancers and their precursors, including esophageal adenocarcinoma (EA) and Barrett's esophagus (BE), conditions for which aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as possible chemopreventive agents; however, little is known about the ability of a biomarker panel to predict progression to cancer nor how NSAID use may modulate progression. We aimed to evaluate somatic genetic abnormalities with NSAIDs as predictors of EA in a prospective cohort study of patients with BE. Methods and Findings Esophageal biopsies from 243 patients with BE were evaluated at baseline for TP53 and CDKN2A (p16) alterations, tetraploidy, and aneuploidy using sequencing; loss of heterozygosity (LOH); methylation-specific PCR; and flow cytometry. At 10 y, all abnormalities, except CDKN2A mutation and methylation, contributed to EA risk significantly by univariate analysis, ranging from 17p LOH (relative risk [RR] = 10.6; 95% confidence interval [CI] 5.2�21.3, p < 0.001) to 9p LOH (RR = 2.6; 95% CI 1.1�6.0, p = 0.03). A panel of abnormalities including 17p LOH, DNA content tetraploidy and aneuploidy, and 9p LOH was the best predictor of EA (RR = 38.7; 95% CI 10.8�138.5, p < 0.001). Patients with no baseline abnormality had a 12% 10-y cumulative EA incidence, whereas patients with 17p LOH, DNA content abnormalities, and 9p LOH had at least a 79.1% 10-y EA incidence. In patients with zero, one, two, or three baseline panel abnormalities, there was a significant trend toward EA risk reduction among NSAID users compared to nonusers (p = 0.01). The strongest protective effect was seen in participants with multiple genetic abnormalities, with NSAID nonusers having an observed 10-y EA risk of 79%, compared to 30% for NSAID users (p < 0.001). Conclusions A combination of 17p LOH, 9p LOH, and DNA content abnormalities provided better EA risk prediction than any single TP53, CDKN2A, or DNA content lesion alone. NSAIDs are associated with reduced EA risk, especially in patients with multiple high-risk molecular abnormalities.
Blount, Patricia L; Maley, Carlo C; Sanchez, Carissa A; Odze, Robert D; Ayub, Kamran; Rabinovitch, Peter S; Vaughan, Thomas L; Reid, Brian J
Vitamin D Receptor Expression and Neoadjuvant Therapy in Esophageal Adenocarcinoma
Esophageal adenocarcinoma carries a poor prognosis. Tumor response to neoadjuvant therapy is a key prognostic factor in patients with adenocarcinoma of the esophagus, but is inconsistent. Identifying tumor characteristics that portend a favorable response to neoadjuvant therapy would be a valuable clinical tool. The anticancer actions of vitamin D and its receptor may have implications. In this study, 15 biopsy specimens were procured retrospectively from patients being treated for adenocarcinoma of the esophagus. The tissue was immunostained for the vitamin D receptor and compared on the basis of response to neoadjuvant therapy. Tumors that did not respond to neoadjuvant therapy had greater expression of VDR than tumors that responded completely. Expression of VDR declined with tumor de-differentiation. The data suggest that a relationship between vitamin D receptor expression and response to neoadjuvant therapy is plausible.
Trowbridge, Ryan; Sharma, Poonam; Hunter, William J.; Agrawal, Devendra K.
Dietary supplement use and risk of neoplastic progression in esophageal adenocarcinoma: a prospective study.
The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339 men and women with histologically confirmed Barrett's esophagus. Participants underwent baseline and periodic follow-up exams, which included endoscopy and self-administered questionnaires on diet, supplement use, and lifestyle characteristics. Use of multivitamins and 4 individual supplements was calculated using time-weighted averages of reported use over the observational period. Cox proportional-hazards models were used to calculate hazard ratios (HR) for each endpoint: EA, tetraploidy, and aneuploidy. During a mean follow-up of 5 yr, there were 37 cases of EA, 42 cases of tetraploidy, and 34 cases of aneuploidy. After controlling for multiple covariates including diet, nonsteroidal anti-inflammatory drug use, obesity, and smoking, participants who took 1 or more multivitamin pills/day had a significantly decreased risk of tetraploidy [HR = 0.19; 95% confidence interval (CI) = 0.08-0.47) and EA (HR = 0.38; 95% CI = 0.15-0.99] compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EA and supplemental vitamin C (> or = 250 mg vs. none: HR = 0.25; 95% CI = 0.11-0.58) and vitamin E (> or = 180 mg vs. none: HR = 0.25; 95% CI = 0.10-0.60). In this cohort study, use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett's esophagus. PMID:18444134
Dong, Linda M; Kristal, Alan R; Peters, Ulrike; Schenk, Jeannette M; Sanchez, Carissa A; Rabinovitch, Peter S; Blount, Patricia L; Odze, Robert D; Ayub, Kamran; Reid, Brian J; Vaughan, Thomas L
Biomarkers in Barrett's esophagus and esophageal adenocarcinoma: Predictors of progression and prognosis
Barrett�s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett�s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett�s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett�s esophagus and EA and to discuss what is required to move the field forward towards clinical application.
Ong, Chin-Ann J; Lao-Sirieix, Pierre; Fitzgerald, Rebecca C
Dietary Factors and the Risks of Esophageal Adenocarcinoma and Barrett's Esophagus
Incidence rates for esophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastroesophageal reflux disease (GERD), obesity, and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of esophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of esophageal adenocarcinoma and its precursor, Barrett�s esophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of esophageal adenocarcinoma, Barrett�s esophagus, and the progression from Barrett�s esophagus to esophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, ?-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark-green, leafy and cruciferous vegetables, carbohydrates, fiber and iron and the risk of esophageal adenocarcinoma and Barrett�s esophagus. Patients at higher risk for Barrett�s esophagus and esophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett�s esophagus to esophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomized chemoprevention trials are warranted for the primary prevention of Barrett�s esophagus or its progression to cancer.
Kubo, Ai; Corley, Douglas A.; Jensen, Christopher D.; Kaur, Rubinder
Lifetime risk of esophageal adenocarcinoma in patients with Barrett's esophagus
AIM: To investigate the lifetime risk of development of esophageal adenocarcinoma and/or high-grade dysplasia in patients diagnosed with Barrett�s esophagus. METHODS: Data were extracted from the United Kingdom National Barrett�s Oesophagus Registry on date of diagnosis, patient age and gender of 7877 patients from who had been registered from 35 United Kingdom centers. Life expectancy was evaluated from United Kingdom National Statistics data based upon gender and age at year at diagnosis. These data were then used with published estimates of annual adenocarcinoma and high-grade dysplasia incidences from meta-analyses and large population-based studies to estimate overall lifetime risk of development of these study endpoints. RESULTS: The mean age at diagnosis of Barrett�s esophagus was 61.6 years in males and 67.3 years in females. The mean life expectancy at diagnosis was 23.1 years in males, 20.7 years in females and 22.2 years overall. Using data from published meta-analyses, the lifetime risk of development of adenocarcinoma was between 1 in 8 and 1 in 14 and the lifetime risk of high-grade dysplasia or adenocarcinoma was 1 in 5 to 1 in 6. Using data from 3 large recent population-based cohort studies the lifetime risk of adenocarcinoma was between 1 in 10 and 1 in 37 and of the combined end-point of high-grade dysplasia and adenocarcinoma was between 1 in 8 and 1 in 20. Age at Barrett�s esophagus diagnosis is reducing and life expectancy is increasing, which will partially counter-balance lower annual cancer incidence. CONCLUSION: There is a significant lifetime risk of development of high-grade dysplasia and adenocarcinoma in Barrett�s esophagus.
Gatenby, Piers; Caygill, Christine; Wall, Christine; Bhatacharjee, Santanu; Ramus, James; Watson, Anthony; Winslet, Marc
Endoscopic therapy for Barrett's esophagus and early esophageal adenocarcinoma.
Endoscopic therapy for Barrett's esophagus is feasible and likely to decrease the future risk of development of esophageal adenocarcinoma. The most commonly used therapy is radiofrequency ablation, which has been shown to produce reproducible superficial injury in the esophagus. Other thermal therapies include multipolar coagulation, argon plasma coagulation, and thermal laser therapy. The other end of the ablative spectrum includes cryotherapy, which involves freezing tissue to produce mucosal necrosis. Photodynamic therapy has been used to photochemically eliminate abnormal mucosa. Endoscopic therapy has been demonstrated to be effective in high-risk situations such as Barrett's esophagus with high-grade dysplasia. PMID:23452637
Leggett, Cadman L; Gorospe, Emmanuel C; Wang, Kenneth K
Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells.
The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17?-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted. PMID:23163347
Sukocheva, O A; Wee, C; Ansar, A; Hussey, D J; Watson, D I
Comparative proteomics analysis of Barrett metaplasia and esophageal adenocarcinoma using two-dimensional liquid mass mapping.
Esophageal adenocarcinoma, currently the seventh leading cause of cancer-related death, has been associated with the presence of Barrett metaplasia. The malignant potential of Barrett metaplasia is evidenced by ultimate progression of this condition to invasive adenocarcinoma. We utilized liquid phase separation of proteins with chromatofocusing in the first dimension and nonporous reverse phase HPLC in the second dimension followed by ESI-TOF mass spectrometry to identify proteins differentially expressed in six Barrett metaplasia samples as compared with six esophageal adenocarcinoma samples; all six Barrett samples were obtained from the identical six patients from whom we obtained the esophageal adenocarcinoma tissue. Approximately 300 protein bands were detected by mass mappings, and 38 differentially expressed proteins were identified by microLC-MS/MS. The false positive rates of the peptide identifications were evaluated by reversed database searching. Among the proteins that were identified, Rho GDP dissociation inhibitor 2, alpha-enolase, Lamin A/C, and nucleoside-diphosphate kinase A were demonstrated to be up-regulated in both mRNA and protein expression in esophageal adenocarcinomas relative to Barrett metaplasia. Candidate proteins were examined at the mRNA level using high density oligonucleotide microarrays. The cellular expression patterns were verified in both esophageal adenocarcinomas and in Barrett metaplasia by immunohistochemistry. These differentially expressed proteins may have utility as useful candidate markers of esophageal adenocarcinoma. PMID:16829691
Zhao, Jia; Chang, Andrew C; Li, Chen; Shedden, Kerby A; Thomas, Dafydd G; Misek, David E; Manoharan, Arun Prasad; Giordano, Thomas J; Beer, David G; Lubman, David M
Endoscopic Therapy of Barrett's Esophagus and Early Esophageal Adenocarcinoma
Summary Endoscopic therapy of Barrett�s esophagus is feasible and likely to decrease the future risk of development of esophageal adenocarcinoma. The most commonly utilized therapy is radiofrequency ablation that has been shown to produce reproducible superficial injury in the esophagus. Other thermal therapies have been performed including multipolar coagulation, argon plasma coagulation, and thermal laser therapy. The other end of the ablative spectrum includes cryotherapy which involves freezing tissue to produce mucosal necrosis. Finally, photodynamic therapy has been used to photochemically eliminate abnormal mucosa. Endoscopic therapy has been demonstrated to be effective in high-risk situations such as Barrett�s esophagus with high-grade dysplasia. Even after the development of early esophageal carcinoma, endoscopic therapy is feasible so long as there are no risk factors for potential metastasis. Although the biological principles of re-epithelialization have not been well elucidated, it appears that adequate control of gastroesophageal reflux is necessary. There is a substantial risk of recurrence even after complete ablation that necessitates continued surveillance after ablation.
Leggett, Cadman L.; Gorospe, Emmanuel C.; Wang, Kenneth K.
Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma
To test the hypothesis that aberrations of DNA repair contribute to susceptibility for the progression of gastro- esophageal reflux disease (GERD) into Barrett esophagus (BE) and esophageal adenocarcinoma (EADC), we studied the frequency of polymorphisms of selected DNA repair genes in patients with GERD (n � 126), BE (n � 125) and EADC (n � 56) enrolled in a 2-year
Alan G. Casson; Zuoyu Zheng; Susan C. Evans; Paul J. Veugelers; Geoffrey A. Porter; Duane L. Guernsey
Expression and Effect of Inhibition of the Ubiquitin-Conjugating Enzyme E2C on Esophageal Adenocarcinoma1
Abstract Ubiquitin-dependent proteolysis of cyclins plays a critical role in cell cycle progression and tumorigenesis. We examined the expression of ubiquitin-conjugating enzyme E2C (UBE2C) during progression from Barrett's metaplasia to esophageal adenocarcinoma (EA) and the effects of targeting this enzyme on EA-derived cell lines. Using oligonucleotide microarrays UBE2C expression was elevated in 73% (11 of 15) of EAs relative to Barrett's metaplasia. Tissue microarray showed elevated UBE2C in 70% (7 of 10) of dysplastic samples and in 87% (58 of 67) of tumors relative to metaplastic samples. Transfection of dominant-negative UBE2C into Seg-1 cells decreased proliferation (P = .04) and increased mitotic arrest compared to vector controls (63.5% vs 6.8%; P < .001). Transfection of UBE2C small interfering RNA also caused inhibiton of cell proliferation and distortion of the cell cycle, with maximal increase of G2 cells (155% of mock cells) at 72 hours and of S-phase cells (308% of mock cells) at 24 hours. Treatment of Seg-1 cells with the proteasome inhibitor MG-262 (1 nM-1 �M) showed decreased proliferation (P = .02). EA-derived cells expressing UBE2C are sensitive to treatment with MG-262 and to silencing of UBE2C, suggesting that patients with EAs overexpressing UBE2C may benefit from agents targeting this ubiquitin-conjugating enzyme.
Lin, Jules; Raoof, Duna A; Wang, Zhuwen; Lin, Mu-Yen; Thomas, Dafydd G; Greenson, Joel K; Giordano, Thomas J; Orringer, Mark B; Chang, Andrew C; Beer, David G; Lin, Lin
Genome-wide DNA Methylation Profiling of Cell-Free Serum DNA in Esophageal Adenocarcinoma and Barrett Esophagus12
Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm) profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n = 8) and matched serum DNA (n = 8), in serum DNA of BE (n = 10), and in healthy controls (n = 10) using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92) in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions.
Zhai, Rihong; Zhao, Yang; Su, Li; Cassidy, Lauren; Liu, Geoffrey; Christiani, David C
Genome-wide DNA methylation profiling of cell-free serum DNA in esophageal adenocarcinoma and Barrett esophagus.
Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm) profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n = 8) and matched serum DNA (n = 8), in serum DNA of BE (n = 10), and in healthy controls (n = 10) using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92) in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions. PMID:22355271
Zhai, Rihong; Zhao, Yang; Su, Li; Cassidy, Lauren; Liu, Geoffrey; Christiani, David C
The Role of Tobacco, Alcohol, and Obesity in Neoplastic Progression to Esophageal Adenocarcinoma: A Prospective Study of Barrett's Esophagus
Background Esophageal adenocarcinoma (EA) incidence in many developed countries has increased dramatically over four decades, while survival remains poor. Persons with Barrett's esophagus (BE), who experience substantially elevated EA risk, are typically followed in surveillance involving periodic endoscopy with biopsies, although few progress to EA. No medical, surgical or lifestyle interventions have been proven to safely lower EA risk. Design We investigated whether smoking, obesity or alcohol could predict progression to EA in a prospective cohort of 411 BE patients. Data were collected during personal interview. Adjusted hazard ratios (HR) were estimated using Cox regression. Results 39% had body mass index (BMI) over 30 and 64% had smoked cigarettes. Main analyses focused on those with at least 5 months of follow-up (33,635 person-months), in whom 45 developed EA. Risk increased by 3% per year of age (trend p-value 0.02), with approximate doubling of risk among males. EA risk increased with smoking pack-years (trend p-value 0.04) and duration (p-value 0.05). Compared to never-smokers, the HR for those in the highest pack-year tertile was 2.29 (95%CI 1.04�5.07). No association was found with alcohol or BMI, whereas a suggestion of increased risk was observed in those with higher waist-hip ratio, especially among males. Conclusion EA risk significantly increased with increasing age and cigarette exposure. Abdominal obesity, but not BMI, was associated with a modest increased risk. Continued follow-up of this and other cohorts is needed to precisely define these relationships so as to inform risk stratification and preventive interventions.
Hardikar, Sheetal; Onstad, Lynn; Blount, Patricia L.; Odze, Robert D.; Reid, Brian J.; Vaughan, Thomas L.
Esophageal Adenocarcinoma in a 40-Year-Old Man With Cystic Fibrosis: Coincidence or Not?
Objective To report a case of esophageal cancer in an adult patient with cystic fibrosis (CF) and review the relationship between these 2 diseases. Case Report A 40-year-old man with CF presented with worsening epigastric pain, weight loss, and upper gastrointestinal (GI) bleeding. Endoscopy revealed innumerable masses in the distal esophagus. The workup revealed esophageal adenocarcinoma metastatic to the liver and the lungs. Discussion Abnormal mucous secretions in CF patients impair the innate GI mucosal barriers. The incidence of both gastroesophageal reflux disease and GI malignancies is higher in patients with CF. Patients with CF now survive long enough to potentially experience the consequences of long-term acid exposure, including esophagitis, Barrett esophagus, and esophageal cancer. Conclusion Our case report adds to a small but growing body of evidence that CF is a significant risk factor for GI malignancies, including esophageal adenocarcinoma. Controlled studies are needed to determine whether a causal relationship truly exists.
Holt, Edward W.; Yimam, Kidist K.; Liberman, Martin S.
Loss of TGF-? Adaptor ?2SP Activates Notch Signaling and SOX9 Expression in Esophageal Adenocarcinoma
TGF-? and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-? signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-? adapter ?2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in esophageal adenocarcinoma patients. Downregulation of ?2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into esophageal adenocarcinoma cells of ?2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in ?2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of ?2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of ?2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-? targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of ?2SP switches TGF-? signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9.
Song, Shumei; Maru, Dipen M.; Ajani, Jaffer A.; Chan, Chia-Hsin; Honjo, Soichiro; Lin, Hui-Kuan; Correa, Arlene; Hofstetter, Wayne L.; Davila, Marta; Stroehlein, John; Mishra, Lopa
Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.
Fujimura, Takashi; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo; Koichi, Miwa; Takanori, Hattori
Inflammation-related carcinogenesis and prevention in esophageal adenocarcinoma using rat duodenoesophageal reflux models.
Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing. PMID:24212953
Fujimura, Takashi; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo; Miwa, Koichi; Hattori, Takanori
Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma
Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival.
Chang, Joe Y. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States)]. E-mail: firstname.lastname@example.com; Zhang Xiaochun [Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Cheung, Rex [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Fang Bingliang [Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
AXL Mediates TRAIL Resistance in Esophageal Adenocarcinoma12
The overexpression of AXL receptor tyrosine kinase is a frequent finding that has been associated with poor prognosis in esophageal adenocarcinoma (EAC). As the majority of EAC are intrinsically resistant to DNA-damaging therapies, an alternative therapeutic approach based on the activation of death receptors may be warranted. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been evaluated in clinical trials and found promising as anticancer agent with mild side effects; unfortunately, resistance to TRAIL remains a major clinical problem. Herein, we explored the role of AXL in TRAIL resistance and elucidated the underlying mechanism. Overexpression of AXL in OE33 and OE19 cells promoted cell survival and attenuated TRAIL-induced cellular and molecular markers of apoptosis. In contrast, knockdown of endogenous AXL sensitized FLO-1 cells to TRAIL. The mechanism by which AXL regulates TRAIL resistance was examined. Protein and mRNA expression of DR4 and DR5 death receptors was not downregulated by AXL. In addition, the possible involvement of FLICE-inhibitory protein (FLIP) in regulating the interaction of caspase-8 with Fas-associated death domain protein (FADD) was excluded, as AXL did not enhance FLIP expression or FLIP/FADD association. Alternatively, protein association of AXL with DR5, independent of TRAIL, was confirmed, suggesting that AXL could regulate DR5 receptor activity. The AXL/DR5 association had no negative effect on TRAIL-induced interaction with FADD. However, the AXL/DR5 interaction blocked the recruitment of caspase-8 to the death-inducing signal complex (DISC). Collectively, our findings uncover a novel mechanism of TRAIL resistance mediated by AXL through regulation of the DISC and provide strong evidence that AXL could be exploited as a therapeutic target to circumvent TRAIL resistance.
Hong, Jun; Belkhiri, Abbes
Area-Level Attributes and Esophageal Adenocarcinoma in Surveillance, Epidemiology and End Results Registries
Purpose To examine the associations between area-level socioeconomic attributes and stage of esophageal adenocarcinoma diagnoses in 16 SEER cancer registries during 2000-2007. Methods Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models to assess the relationship between distant-stage esophageal adenocarcinoma and individual, census tract, and county-level attributes. Results Among cases with data on birthplace, no significant association was seen between reported birth within versus outside the United States and distant-stage cancer (adjusted OR=1.02, 95% CI: 0.85-1.22). Living in an area with a higher percentage of residents born outside the United States than the national average was associated with distant-stage esophageal adenocarcinoma; census tract level: >11.8%, (OR=1.10, 95% CI:1.01�1.19), county level: >11.8%, (OR=1.14, 95% CI:1.05-1.24). No association was observed between median household income and distant-stage cancer at either census tract or county levels. Conclusion The finding of greater odds of distant-stage esophageal adenocarcinoma among cases residing in SEER areas with higher proportion of non-U.S. Natives suggests local areas where esophageal cancer control efforts might be focused. Missing data at the individual level was a limitation of the present study. Furthermore, inconsistent associations with foreign birth at individual- versus area-levels cautions against using area-level attributes as proxies for case attributes.
Ghazarian, Armen A.; Murphy, Megan A.; Khan, Maria R.; Saksvig, Brit I.; Altekruse, Sean F.
Effect of aspirin treatment on the prevention of esophageal adenocarcinoma in a rat experimental model.
Aspirin has been proposed in recent years as a candidate for chemoprevention of adenocarcinoma in patients with Barrett's esophagus. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) in an experimental model of esophageal adenocarcinoma. An animal model of gastroenteroesophageal reflux was established using Wistar rats undergoing esophagojejunostomy with gastric preservation. Following surgery, rats were divided into three groups: i) control (vehicle); ii) ASA 50�mg/kg/day; and iii) ASA 5�mg/kg/day. Four months after surgery, the surviving animals were sacrificed and the rat esophagi were assessed for histological and biochemical [prostaglandin E2 (PGE2) and lipoxin A4 (LXA4 ) levels] analysis. As in the control rats, those receiving aspirin treatment showed no decrease in inflammation grade, extent of ulcerated esophageal mucosa, length of intestinal metaplasia in continuity with anastomosis, presence of intestinal metaplasia beyond anastomosis, severity of dysplasia or incidence of adenocarcinoma. In contrast, aspirin-treated rats showed decreased esophageal tissue levels of PGE2 and increased LXA4, significantly in the high-dose aspirin group (p=0.008 and p=0.01, respectively). In this rat model of gastroesophageal reflux, the administration of aspirin modified esophageal tissue levels of PGE2 and LXA4, but was not effective in preventing the development of esophageal adenocarcinoma. PMID:24737143
Esquivias, Paula; Cebri�n, Carmelo; Morandeira, Antonio; Santander, Sonia; Ortego, Javier; Garc�a-Gonz�lez, Mar�a Asunci�n; Lanas, Angel; Piazuelo, Elena
GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas
Condensed Abstract In a population-based case-control study in the U.S., we examined risks of histologically confirmed esophageal and gastric adenocarcinomas in relation to polymorphisms of the following genes: GSTP; GSTM1; GSTT1; NAT1; and CYP1A1. For the GSTP1 Val/Val genotype (vs. Ile/Ile), the respective ORs of esophageal, cardia, and other gastric adenocarcinomas were 1.73 (0.75�4.02), 1.46 (0.57�3.73), and 1.22 (0.48�3.09), while no consistent patterns of elevated risk were associated with the null GSTM1 or GSTT1 genotypes, one or two copies of NAT1*10 or *11 alleles, or CYP1A1 Val/Val or Ile/Val genotypes (vs. Ile/Ile). Background Polymorphisms in glutathione-S-transferase (GST), N-acetyltransferase (NAT) 1, and CYP1A1 genes have been suggested as susceptibility factors for esophageal and gastric adenocarcinomas, but have not been consistently linked to elevated risks. In a population-based case-control study, we examined risks in relation to polymorphisms of the following genes: GSTP; GSTM1; GSTT1; NAT1; and CYP1A1. Methods Histologically confirmed incident cases, ages 30�79, were identified in three U.S. locations. Population controls from the same catchment areas were frequency matched to expected age and sex distributions of esophageal and gastric cardia adenocarcinomas. DNA was extracted from buffy coat for PCR-based assays, with interpretable genotyping results obtained from 209 controls, 67 esophageal adenocarcinomas, 60 gastric cardia adenocarcinomas, and 56 noncardia gastric adenocarcinomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated among whites, adjusting for age, sex, and study center. Results In all histologic subgroups, ORs were somewhat elevated for the GSTP1 Val/Val genotype (vs. Ile/Ile), although 95% CIs included 1.00. The respective ORs for esophageal, cardia, and other gastric adenocarcinomas were 1.73 (0.75�4.02), 1.46 (0.57�3.73), and 1.22 (0.48�3.09). No consistent patterns of elevated risk were associated with the null GSTM1 or GSTT1 genotypes, one or two copies of NAT1*10 or *11 alleles, or CYP1A1 Val/Val or Ile/Val genotypes (vs. Ile/Ile). Conclusions Additional research in larger samples is needed to further assess polymorphisms and their interactions with epidemiologic risk factors, particularly for esophageal adenocarcinoma, which has been increasing markedly in incidence.
Wideroff, Louise; Vaughan, Thomas L.; Farin, Federico M.; Gammon, Marilie D.; Risch, Harvey; Stanford, Janet L.; Chow, Wong-Ho
Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis
Background Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). Methods We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results The analysis included 9 studies (4 cohort, 5 case�control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2?=?47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2?=?0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose�response relationship. Conclusions Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC.
Scalp metastasis of gastro-esophageal junction adenocarcinoma: a rare occurrence.
Cutaneous metastasis is one of the many skin changes which are associated with internal malignancies. Breast, lung, and colon are the most common sources of internal primary malignancies. Gastro-esophageal junction adenocarcinoma is a rare cause of cutaneous metastasis to the scalp. Gastric adenocarcinoma usually metastasizes to the liver, peritoneal cavity and regional lymph nodes more often than to skin. We are presenting a case of cutaneous metastasis on the scalp of a 79-year-old man, who was diagnosed and operated for gastro-oesophageal junction adenocarcinoma one year back. PMID:24701517
Roy, Asitava Deb; Sherparpa, Mingma; Prasad, P R K; Lamichanet, Rachna
Biomarkers may help predict progression of Barrett's esophagus to esophageal adenocarcinoma
A series of microRNA expression signatures that may help to define progression of the precancerous condition Barrett's esophagus into esophageal adenocarcinoma was reported recently in Cancer Prevention Research, a journal of the American Association for Cancer Research. The study was conducted by researchers at the University of Texas MD Anderson Cancer Center, in Houston.
The importance of delivery rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett's and Esophageal Adenocarcinoma Consortium
Background Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. Methods The authors pooled data from 12 case-control studies from the Barrett�s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1,242 (EAC), 1,263 (EGJA) and 954 (ESCC) cases and 7,053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. Results For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). Conclusions Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.
Lubin, Jay H.; Cook, Michael B.; Pandeya, Nirmala; Vaughan, Thomas L.; Abnet, Christian C.; Giffen, Carol; Webb, Penelope M.; Murray, Liam J.; Casson, Alan G.; Risch, Harvey A.; Ye, Weimin; Kamangar, Farin; Bernstein, Leslie; Sharp, Linda; Nyren, Olof; Gammon, Marilie D.; Corley, Douglas A.; Wu, Anna H.; Brown, Linda M.; Chow, Wong-Ho; Ward, Mary H.; Freedman, Neal D.; Whiteman, David C.
A quantitative investigation of fucosylated serum glycoproteins with application to esophageal adenocarcinoma.
Although glycoproteomic studies provide unique opportunities for cancer research, it has been necessary to develop specific methods for analysis of oncologically interesting glycoproteins. We describe a general, multimethodological approach for quantitative glycoproteomic analysis of fucosylated glycoproteins in human blood serum. A total of 136 putative fucosylated glycoproteins were identified with very high confidence in three clinically relevant sample pools (N=5 for each), with a mean CV of 3.1% observed for replicate analyses. Two samples were collected from subjects diagnosed with esophagus disease states, high-grade dysplasia plus esophageal adenocarcinoma, while the third sample was representative of a disease-free condition. Some glycoproteins, observed to be significantly upregulated in esophageal adenocarcinoma, i.e. more than twofold higher than in the disease-free condition, are briefly discussed. Further investigation will be necessary to validate these findings; however, the method itself is demonstrated to be an effective tool for quantitative glycoproteomics of clinical samples. PMID:20446296
Mann, Benjamin; Madera, Milan; Klouckova, Iveta; Mechref, Yehia; Dobrolecki, Lacey E; Hickey, Robert J; Hammoud, Zane T; Novotny, Milos V
Patient Preferences for the Chemoprevention of Esophageal Adenocarcinoma in Barrett's Esophagus
OBJECTIVES:Although evidence suggests that aspirin and celecoxib may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE), these drugs can also cause harmful side effects. Our aim was to determine and characterize preferences for these two drugs in patients with BE.METHODS:Preferences data were collected from recruited BE patients using a customized questionnaire, which incorporated standard risk
Chin Hur; Darcy E. Broughton; Elissa Ozanne; Patrick Yachimski; Norman S. Nishioka; G. Scott Gazelle
GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas
Background: Polymorphisms in glutathione-S-transferase (GST), N-acetyltransferase (NAT) 1, and CYP1A1 genes have been suggested as susceptibility factors for esophageal and gastric adenocarcinomas, but have not been consistently linked to elevated risks. In a population-based case�control study, we examined risks in relation to polymorphisms of the following genes: GSTP1; GSTM1; GSTT1; NAT1; and CYP1A1. Methods: Histologically confirmed incident cases, ages 30�79,
Louise Wideroff; Thomas L. Vaughan; Federico M. Farin; Marilie D. Gammon; Harvey Risch; Janet L. Stanford; Wong-Ho Chow
Infrared light-absorbing gold/gold sulfide nanoparticles induce cell death in esophageal adenocarcinoma.
Gold nanoparticles and near infrared-absorbing light are each innocuous to tissue but when combined can destroy malignant tissue while leaving healthy tissue unharmed. This study investigated the feasibility of photothermal ablation therapy for esophageal adenocarcinoma using chitosan-coated gold/gold sulfide (CS-GGS) nanoparticles. A rat esophagoduodenal anastomosis model was used for the in vivo ablation study, and three human esophageal cell lines were used to study the response of cancer cells and benign cells to near infrared light after treatment with CS-GGS. The results indicate that both cancerous tissue and cancer cells took up more gold nanoparticles and were completely ablated after exposure to near infrared light. The benign tissue and noncancerous cells showed less uptake of these nanoparticles, and remained viable after exposure to near infrared light. CS-GGS nanoparticles could provide an optimal endoluminal therapeutic option for near infrared light ablation of esophageal cancer. PMID:23818775
Li, Yan; Gobin, Andre M; Dryden, Gerald W; Kang, Xinqin; Xiao, Deyi; Li, Su Ping; Zhang, Guandong; Martin, Robert C G
Infrared light-absorbing gold/gold sulfide nanoparticles induce cell death in esophageal adenocarcinoma
Gold nanoparticles and near infrared-absorbing light are each innocuous to tissue but when combined can destroy malignant tissue while leaving healthy tissue unharmed. This study investigated the feasibility of photothermal ablation therapy for esophageal adenocarcinoma using chitosan-coated gold/gold sulfide (CS-GGS) nanoparticles. A rat esophagoduodenal anastomosis model was used for the in vivo ablation study, and three human esophageal cell lines were used to study the response of cancer cells and benign cells to near infrared light after treatment with CS-GGS. The results indicate that both cancerous tissue and cancer cells took up more gold nanoparticles and were completely ablated after exposure to near infrared light. The benign tissue and noncancerous cells showed less uptake of these nanoparticles, and remained viable after exposure to near infrared light. CS-GGS nanoparticles could provide an optimal endoluminal therapeutic option for near infrared light ablation of esophageal cancer.
Li, Yan; Gobin, Andre M; Dryden, Gerald W; Kang, Xinqin; Xiao, Deyi; Li, Su Ping; Zhang, Guandong; Martin, Robert CG
Clinicopathologic and prognostic factors of young and elderly patients with esophageal adenocarcinoma: is there really a difference?
Evidence suggests a significant difference in the incidence, presentation, and outcome of young and elderly patients with esophageal adenocarcinoma. We aimed to compare clinicopathologic and prognostic factors of young and elderly patients with esophageal adenocarcinoma at a surgical department in Europe. From 1996 to 2006, 223 patients with a resectable esophageal adenocarcinoma were analyzed and divided in three groups: (i) patients
Vallb�hmer, D; H�lscher, A H; Brabender, J; Prenzel, K; Gutschow, C; Schr�der, W; Metzger, R; Bollschweiler, E
Aberrantly methylated PKP1 in the progression of Barrett's esophagus to esophageal adenocarcinoma
The aberrant DNA methylation of tumor suppressor genes occurs frequently in Barrett�s esophagus (BE) and esophageal adenocarcinoma (EAC) and likely affects the initiation and progression of BE to EAC. In the present study we discovered PKP1 as a novel methylated gene in EAC and then investigated the role of loss of PKP1, a constituent of the desmosome complex found in stratified epithelial layers, on the behavior of Barrett�s esophagus and esophageal adenocarcinoma cells. Using primary esophageal tissue samples, we determined that PKP1 was rarely methylated in normal squamous esophagus (5/55; 9.1%) and BE (5/39; 12.8%) and more frequently methylated in Barrett�s esophagus with high-grade dysplasia (HGD) or EAC (20/60; 33.3%; p<0.05). Furthermore, PKP1 levels were decreased in BE and HGD/EAC cases compared to normal squamous esophagus cases. Knockdown of PKP1 in the BE cell lines CP-A and CP-D (both normally express PKP1) resulted in increased cell motility. Thus, PKP1 loss secondary to promoter methylation, as well as other mechanisms, may promote the progression of BE to EAC in a subset of patients via decreased desmosome assembly and increased cell motility.
Kaz, AM; Luo, Y; Dzieciatkowski, S; Chak, A; Willis, JE; Upton, MP; Leidner, RS; Grady, WM
Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk
Purpose��Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated\\u000a with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and\\u000a base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased\\u000a the risk of esophageal adenocarcinoma.\\u000a \\u000a \\u000a \\u000a Methods��DNA
Darren Tse; Rihong Zhai; Wei Zhou; Rebecca S. Heist; Kofi Asomaning; Li Su; Thomas J. Lynch; John C. Wain; David C. Christiani; Geoffrey Liu
The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma.
Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and tumor development, and this pathway has not been well studied in human esophageal carcinomas. Esophageal cancer is one of the human cancers with the worst prognosis and has two main histologies: squamous cell carcinomas (ESCC) and adenocarcinoma (EAC). Previously, we have reported that detection of the IGF axis may be useful for the prediction of recurrence and poor prognosis of ESCC. We have also shown the successful therapy for several gastrointestinal cancers using recombinant adenoviruses expressing dominant negative IGF-IR (ad-IGF-IR/dn). The aim of this study is to develop potential targeted therapeutics to IGF-IR and to assess the effect of IGF-IR blockade in both of these types of esophageal cancer. We determined immunohistochemical expression of IGF-IR in a tissue microarray. We then assessed the effect of IGF-IR blockade on signal transduction, proliferation, apoptosis, and motility. Ad-IGF-IR/dn, a tyrosine kinase inhibitor, BMS-536924, and adenovirus expressing shRNA for IGF-IR were used. IGF-IR expression was common in both tumor types but not in normal tissues. IGF-IR was detected in metastatic sites at similar levels compared to the primary site. IGF-IR inhibition suppressed proliferation and colony formation in both cancers. IGF-IR blockades up-regulated both stress- and chemotherapy-induced apoptosis and reduced migration. Although IGF-IR/dn blocked ligand-induced activation of Akt-1 mainly, BMS-536924 effectively blocked both activation of Akt and MAPK. The IGF axis might play a key role in tumor progression of esophageal carcinomas. The IGF-IR targeting strategies might thus be useful anticancer therapeutics for human esophageal malignancies. PMID:24026884
Adachi, Yasushi; Ohashi, Hirokazu; Imsumran, Arisa; Yamamoto, Hiroyuki; Matsunaga, Yasutaka; Taniguchi, Hiroaki; Nosho, Katsuhiko; Suzuki, Hiromu; Sasaki, Yasushi; Arimura, Yoshiaki; Carbone, David P; Imai, Kohzoh; Shinomura, Yasuhisa
Cyclin E involved in early stage carcinogenesis of esophageal adenocarcinoma by SNP DNA microarray and immunohistochemical studies
Background Cyclin E is a cell cycle regulator which is critical for driving G1/S transition. Abnormal levels of cyclin E have been found in many cancers. However, the level changes of cyclin E in esophageal adenocarcinoma and its precancerous lesion have not been well studied. Here, we focus on the gene amplification and expression of cyclin E in these lesions, and aim to ascertain the relationship with clinicopathological characteristics. Methods Genomic DNA was analyzed from 116 esophageal adenocarcinoma and 26 precancerous lesion patients using Affymetrix SNP 6.0 arrays. The protein overexpression of cyclin E was also detected using immunohistochemistry from tissue microarrays containing esophageal adenocarcinoma and precancerous lesions. Patient survival and other clinical data were collected and analyzed. The intensity and percentage of the cyclin E expressing cells in tissue microarrays were scored by two pathologists. Fisher exact tests and Kaplan-Meier methods were used to analyze data. Results By genomic analysis, cyclin E was amplified in 19.0% of the EAC samples. By immunohistochemistry, high expression of cyclin E was observed in 2.3% of squamous mucosa tissues, 3.7% in columnar cell metaplasia, 5.8% in Barrett�s esophagus, 19.0% in low grade dysplasia, 35.7% in high grade dysplasia, and 16.7% in esophageal adenocarcinoma. The differences in cyclin E high expression between neoplastic groups and non-dysplasia groups are statistically significant (p?0.05). The prognosis for patients with high cyclin E expression appeared slightly better than for those with low cyclin E expression although this was not statistically significant (p?=?0.13). Conclusions The expression of cyclin E significantly increases from non-dysplasia esophageal lesion to low and high grade dysplasia, suggesting that cyclin E plays an important role in the early stage of carcinogenesis. Importantly, cyclin E is also amplified and highly expressed in a subset of esophageal adenocarcinoma patients, but this increase is not associated with worse prognosis.
Outcomes of induction chemotherapy followed by chemoradiation using intensity-modulated radiation therapy for esophageal adenocarcinoma.
This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity-modulated radiation therapy (IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan-Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease. PMID:23796070
Gerber, N; Ilson, D H; Wu, A J; Janjigian, Y Y; Kelsen, D P; Zheng, J; Zhang, Z; Bains, M S; Rizk, N; Rusch, V W; Goodman, K A
Helicobacter pylori induces apoptosis in Barrett's-derived esophageal adenocarcinoma cells.
Helicobacter pylori may protect against the development of dysplasia in Barrett's epithelium of patients with gastroesophageal reflux disease. The aim of this study was to determine whether H. pylori preferentially induces apoptosis in Barrett's-derived cancer cells compared to normal cells. A Barrett's-derived adenocarcinoma cell line (OE33) was grown. H. pylori wild-type, isogenic vacA-, cagA(-), and picB-/cagE- mutant strains were grown on agar plates. Intact or sonicated bacteria were used to treat normal and OE33 cells for 24 hours, and Hoechst dye binding was performed to measure apoptosis. FAS protein expression was determined by Western immunoblotting. OE33 cells treated with intact H. pylori wild-type strains produced significant (P < 0.05) dose-dependent increases in apoptosis compared to normal esophageal cells. H. pylori wild-type and vacA- isogenic strains were more effective than cagA- and picB-/cage- isogenic strains in inducing apoptosis in OE33 cells. In OE33 cells, H. pylori sonicates produced lower levels of apoptosis than intact bacteria. Wild-type H. pylori strains increased Fas protein expression in OE33 cells at 18 hours. H. pylori induced apoptosis at a higher rate in the Barrett's-derived human esophageal adenocarcinoma cells than in normal esophageal cells. The H. pylori-induced apoptosis was primarily dependent on intact bacteria and the presence of the cagA and picB/cagE gene products. H. pylori-induced apoptosis may involve the Fas-caspase cascade. PMID:12559187
Jones, Andrew D; Bacon, Kathy D; Jobe, Blair A; Sheppard, Brett C; Deveney, Clifford W; Rutten, Michael J
NADPH Oxidase NOX5-S and Nuclear Factor ?B1 Mediate Acid-Induced Microsomal Prostaglandin E Synthase-1 Expression in Barrett's Esophageal Adenocarcinoma Cells
The mechanisms of progression from Barrett�s esophagus (BE) to esophageal adenocarcinoma (EA) are not known. Cycloxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has been shown to be important in esophageal tumorigenesis. We have shown that COX-2 mediates acid-induced PGE2 production. The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known. We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells. Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA. Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation. Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor ?B (NF-?B) in vivo activation reporter plasmid pNF-?B-Luc. Knockdown of NF-?B1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Two novel NF-?B binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter. We conclude that mPGES1 mediates acid-induced increase in PGE2 production and cell proliferation. Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-?B1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA.
Zhou, Xiaoxu; Li, Dan; Resnick, Murray B.; Wands, Jack
Vitamin D receptor is highly expressed in precancerous lesions and esophageal adenocarcinoma with significant sex difference.
Bile acid reflux into the esophagus is important in the development of esophageal adenocarcinoma (EAC). Recently, vitamin D receptor (VDR) was recognized as a bile acid receptor as well as a vitamin receptor. Expression of VDR is reported to influence the development of various types of cancer, such as those of the breast, liver, and colon. However, little is known about the role of VDR in esophageal neoplasms. We investigated the clinicopathological role of VDR in esophageal tumors. We analyzed genomic DNA from 116 EACs for copy number aberrations. The VDR locus was amplified in 7% of EACs. Expression of the VDR protein was also detected by immunohistochemistry from tissue microarrays created from tissues of Barrett esophagus (BE), low-grade (LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CCM), squamous epithelium (SE), EAC, and esophageal squamous cell carcinoma (ESCC). The protein was highly expressed in 88% of CCM (58/66), 95% of BE (35/37), 100% of the 19 LGD, 94% of HGD (15/16), and 79% of EAC (86/109), but expression in SE and ESCC was rare. Female patients with EAC and CCM were significantly less likely to have high VDR expression than male patients. The overall survival rate was significantly different for patients with tumors exhibiting VDR amplification versus nonamplification. Our findings suggest that VDR plays a role in the early development of EAC through a bile acid ligand. The sex difference in VDR expression may help to explain why men have a high incidence of EAC. PMID:24951052
Zhou, Zhongren; Xia, Yinglin; Bandla, Santhoshi; Zakharov, Vladislav; Wu, Shaoping; Peters, Jeffery; Godfrey, Tony E; Sun, Jun
A Quantitative Investigation of Fucosylated Serum Glycoproteins with Application to Esophageal Adenocarcinoma
Whereas glycoproteomic studies provide unique opportunities for cancer research, it has been necessary to develop specific methods for analysis of oncologically interesting glycoproteins. We describe a general, multimethodological approach for quantitative glycoproteomic analysis of fucosylated glycoproteins in human blood serum. A total of 136 putative fucosylated glycoproteins were identified with very high confidence in three clinically relevant sample pools (N=5 for each), with a mean coefficient of variation of 3.1% observed for replicate analyses. Two samples were collected from subjects diagnosed with esophagus disease states, high-grade dysplasia (HGD) plus esophageal adenocarcinoma (EAC), while the third sample was representative of a disease-free (DF) condition. Some glycoproteins, observed to be significantly upregulated in EAC, i.e. more than 2-fold higher than in the DF condition, are briefly discussed. Further investigation will be necessary to validate these findings; however, the method itself is demonstrated to be an effective tool for quantitative glycoproteomics of clinical samples.
Mann, Benjamin; Madera, Milan; Klouckova, Iveta; Mechref, Yehia; Dobrolecki, Lacey E.; Hickey, Robert J.; Hammoud, Zane T.; Novotny, Milos V.
Environmental Causes of Esophageal Cancer
Synopsis This articles reviews the environmental risk factors and predisposing conditions for the two main histological types of esophageal cancer, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). Tobacco smoking, excessive alcohol consumption, drinking mat�, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of ESCC. Results of investigations on several other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are also discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and probably absence of H. pylori in the stomach increase the risk of EA. Results of studies investigating other factors, including low intake of fresh fruits and vegetables, consumption of carbonated soft drink, use of H2 blockers, non-steroidal anti-inflammatory drugs, and drugs that relax the lower esophageal sphincter are also discussed.
Kamangar, Farin; Chow, Wong-Ho; Abnet, Christian; Dawsey, Sanford
Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats.
Several epidemiological cohort studies have suggested that duodeno-gastroesophageal reflux per se induces Barrett's esophagus leading to increased risk of the development of esophageal adenocarcinoma (EAC). However, the exact causative factors behind EAC remain unclear. Recently, we designed a new duodenal contents reflux model which retained normal stomach function. In this model, duodenal contents flowed back into the esophagus and stomach resulting in repeated re-entry into the esophagus through the site of esophagojejunostomy. To elucidate the factors underlying the development of EAC, thiazolidine-4-carboxylic acid (thioproline, TPRO) was applied to the new reflux models as a nitrite scavenger and as a probe to detect reactive nitrogen species (RNS). Post-operatively, 31 animals were divided into two groups according to diet. Animals belonging to the control group were given normal diet (n = 18), while the TPRO group was given food containing 0.5% TPRO (n = 13). All esophageal sections in both groups were examined using hematoxylin and eosin staining and immunohistochemical analysis of inducible nitric oxide synthase (iNOS). EACs developed in 7 of 18 rats (38.9%) of the control group, whereas no EACs were detected in the TPRO group (Fisher's exact test, P < 0.05). Conversely, esophageal squamous cell carcinoma (ESCC) was detected in 1 of 18 rats (5.6%) of the control group and in 1 of 13 rats (7.7%) of the TPRO group. The incidence of ESCC was not significantly different between the two groups (P = 0.671). iNOS protein was overexpressed in Barrett's esophagus of both groups. The present results suggest that RNS such as nitric oxide and peroxynitrite and nitroso compounds derived from reflux of duodenal contents play an important role in the development of EAC, and that the primary causes of ESCC and EAC may differ. PMID:14754873
Kumagai, Hitomi; Mukaisho, Ken-ichi; Sugihara, Hiroyuki; Miwa, Koichi; Yamamoto, Gaku; Hattori, Takanori
Role of intracellular calcium and NADPH oxidase NOX5-S in acid-induced DNA damage in Barrett's cells and Barrett's esophageal adenocarcinoma cells.
Mechanisms whereby acid reflux may accelerate the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. Acid and reactive oxygen species (ROS) have been reported to cause DNA damage in Barrett's cells. We have previously shown that NADPH oxidase NOX5-S is responsible for acid-induced H2O2 production in Barrett's cells and in EA cells. In this study we examined the role of intracellular calcium and NADPH oxidase NOX5-S in acid-induced DNA damage in a Barrett's EA cell line FLO and a Barrett's cell line CP-A. We found that pulsed acid treatment significantly increased tail moment in FLO and CP-A cells and histone H2AX phosphorylation in FLO cells. In addition, acid treatment significantly increased intracellular Ca(2+) in FLO cells, an increase that is blocked by Ca(2+)-free medium with EGTA and thapsigargin. Acid-induced increase in tail moment was significantly decreased by NADPH oxidase inhibitor diphenylene iodonium in FLO cells, and by blockade of intracellular Ca(2+) increase or knockdown of NOX5-S with NOX5 small-interfering RNA (siRNA) in FLO and CP-A cells. Acid-induced increase in histone H2AX phosphorylation was significantly decreased by NOX5 siRNA in FLO cells. Conversely, overexpression of NOX5-S significantly increased tail moment and histone H2AX phosphorylation in FLO cells. We conclude that pulsed acid treatment causes DNA damage via increase of intracellular calcium and activation of NOX5-S. It is possible that in BE acid reflux increases intracellular calcium, activates NOX5-S, and increases ROS production, which causes DNA damage, thereby contributing to the progression from BE to EA. PMID:24699332
Li, Dan; Cao, Weibiao
Cancer - esophagus ... Esophageal cancer is not common in the United States. It occurs most often in men over 50 years old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types ...
Mapping of homozygous deletions in verified esophageal adenocarcinoma cell lines and xenografts.
Human esophageal adenocarcinoma (EAC) cell lines and xenografts are powerful tools in the search for genetic alterations because these models are composed of pure human cancer cell populations without admixture of normal human cells. In particular detection of homozygous deletions (HDs) is easier using these pure populations of cancer cells. Identification of HDs could potentially lead to the subsequent identification of new tumor suppressor genes (TSGs) involved in esophageal adenocarcinogenesis. Genome wide single nucleotide polymorphism (SNP) arrays were used to identify HDs in 10 verified EAC cell lines and nine EAC xenografts. In total, 61 HDs (range 1-6 per sample) were detected and confirmed by polymerase chain reaction. Besides HDs observed in common fragile genomic regions (n = 26), and gene deserts (n = 8), 27 HDs were located in gene-containing regions. HDs were noted for known TSGs, including CDKN2A, SMAD4 and CDH3/CDH1. Twenty-two new chromosomal regions were detected harboring potentially new TSGs involved in EAC carcinogenesis. Two of these regions of homozygous loss, encompassing the ITGAV and RUNX1 gene, were detected in multiple samples indicating a potential role in the carcinogenesis of EAC. To exclude culturing artifacts, these last two deletions were confirmed by fluorescent in situ hybridization in the primary tumors of which the involved cell lines and xenografts were derived. In summary, in this report we describe the identification of HDs in a series of verified EAC cell lines and xenografts. The deletions documented here are a step forward identifying the key genes involved in EAC development. PMID:22081516
Boonstra, Jurjen J; van Marion, Ronald; Douben, Hannie J C W; Lanchbury, Jerry S; Timms, Kirsten M; Abkevich, Victor; Tilanus, Hugo W; de Klein, Annelies; Dinjens, Winand N M
Regulation of Desmocollin3 Expression by Promoter Hypermethylation is Associated with Advanced Esophageal Adenocarcinomas
BACKGROUND: Desmocollin3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and plays an important role in tumor invasion and metastasis. In this study, we investigated the epigenetic mechanism that regulates DSC3 expression in esophageal adenocarcinomas (EACs). METHODS: Expression of DSC3 was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The promoter DNA methylation level of DSC3 was examined using quantitative bisulfite pyrosequencing. RESULTS: The qRT-PCR analysis demonstrated significant down-regulation of the DSC3 mRNA levels in human EAC cell lines and tissue samples (P<.001). In addition, the EAC cell lines and tumor samples have aberrant promoter hypermethylation as compared to normal esophageal samples (P<.001). DSC3 promoter hypermethylation (>10% methylation level) was detected in 97.5% (39/40) of EAC samples whereas none of the normal tissue samples showed hypermethylation (P<.0001). There was a significant inverse correlation between promoter DNA methylation levels and mRNA expression folds for DSC3 (coefficient r=-0.685, P<.0001). Treatment of FLO-1 and SKGT4 EAC cells with 5-Aza-deoxytidine led to a significant reduction in the promoter DNA methylation levels with restoration of the DSC3 expression, suggesting that promoter DNA methylation is a key epigenetic mechanism regulating DSC3 expression. High DSC3 promoter DNA methylation levels were significantly correlated with advanced tumor stage (P<.001) and lymph node metastasis (P<.001). CONCLUSION: Taken together, our results demonstrate that epigenetic silencing of DSC3 is a frequent finding in EAC that is possibly associated with advanced stages.
Wang, Qinggang; Peng, DunFa; Zhu, Shoumin; Chen, Zheng; Hu, TianLing; Soutto, Mohammed; Saad, Rama; Zhang, Shutian; EI-Rifai, Wael
Paget cells in the esophagus: assessment of their histopathologic features and near-universal association with underlying esophageal adenocarcinoma.
Pagetoid spread of primary esophageal melanomas and several cases of pagetoid esophageal squamous cell carcinoma are known. However, true esophageal Paget disease (intraepithelial growth of neoplastic cells with glandular differentiation) has only rarely been reported. We encountered 3 endoscopic biopsy specimens containing Paget cells in squamous epithelium associated with adenocarcinomas in Barrett esophagus (BE) and in the esophagogastric junction. To determine the prevalence of Paget cells in the esophagus, we studied 81 endoscopic mucosal resections and 27 esophagectomies from patients with invasive or intramucosal adenocarcinoma, and compared the findings to a control group of 47 endoscopic mucosal resections and 25 esophagectomies from patients with high-grade dysplasia in BE. Paget cells were present in squamous epithelium overlying 5 (4.9%) of 108 adenocarcinomas but in none (0%) of 72 BE with high-grade dysplasia (P=0.16). A computerized search for primary Paget disease using the terms "Paget's and esophagus" or "pagetoid and esophagus" from 1994 to 2007 did not yield any additional cases. Among the 8 patients with Paget cells (including the 2 index biopsies) there were no differences in either sex distribution (7M:1F) or age (mean 62.4 y) as compared with 103 adenocarcinomas without Paget cells (93M:10F, P=0.58; mean age 69.2 y, P=0.78). Morphologically, all adenocarcinomas with Paget cells contained at least a component of diffuse, poorly differentiated adenocarcinoma, and 1 was a signet ring cell carcinoma. Paget cells involved only squamous epithelium directly above the poorly differentiated tumor foci. Histochemistry for periodic acid-Schiff with diastase (PAS-D) and mucicarmine, and immunohistochemistry for CK7, CK20, p53, and E-cadherin, were performed on 7 Paget cases with the following results: PAS-D+ (7 of 7, 100%), mucicarmine+ (6 of 7, 86%), CK7+ (7 of 7, 100%), CK20+ (5 of 7, 71%), p53 overexpression (3 of 7, 43%), and E-cadherin loss (complete loss in 1 and faint expression in 3, 57%). Overall, PAS-D was the most efficacious stain for highlighting Paget cells. A control group of 19 adenocarcinomas without Paget cells were also stained for E-cadherin; only 1 showed faint expression (5%) and none showed complete loss (P=0.01). These results demonstrate a low but significant prevalence (4.9%) of Paget cells in esophageal and esophagogastric junction adenocarcinomas. Unlike previously described cases of mammary, vulvar, and perianal Paget disease, esophageal Paget cells are almost universally associated with underlying adenocarcinoma and not with high grade dysplasia ("in situ" disease) or primary Paget disease. A commonality among cases with Paget cells is the presence of focal or diffuse, poorly differentiated adenocarcinoma with discohesive cells. E-cadherin alterations seem to play a less significant role. PMID:18496141
Abraham, Susan C; Wang, Huamin; Wang, Kenneth K; Wu, Tsung-Teh
Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal adenocarcinoma
Background Barrett's esophagus (BE) is caused by gastroesophageal reflux with consecutive mucosal inflammation, predisposing patients to the development of esophageal adenocarcinoma (EAC). We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography, a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function. Results Biopsies were taken during endoscopy from BE, EAC, and normal control tissue, and proteomic microscopy was performed on 32 different epitopes. When the significance level was set to p < 0.0005 and the search depth to five antibody combinations, controls and BE can be differentiated by 63, controls and EAC by 3222, and BE from EAC by 1521 distinct protein combinations. For example, the number of activated apoptotic na�ve and memory T cells was significantly increased only in BE, whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC. In contrast, the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC. Confirming different pathways in BE and EAC, the number of T lymphocytes with p53 expression and downregulation of bcl2 expression (CD3+p53+Bcl2-NfkB-) was significantly increased in EAC compared to BE and controls. Interestingly, the number of precursor T cells (CD7+) was significantly elevated only in EAC. These cells lack Bax and caspase-8, suggesting impaired apoptosis in the early stages of T cell differentiation. Conclusion Proteomic analysis showed for the first time that proteins, which are critically involved in the mucosal immune system of the esophagus, are distinctly expressed in BE and EAC, whereas others are comparably altered in both diseases, suggesting that many pathogenic events might be shared by both diseases. Topological proteomic analysis, therefore, helps us to understand the different pathogenic events in the underlying disease pathways.
Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Stage IB Esophageal Cancer; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer
2-Methoxyestradiol inhibits Barrett's Esophageal Adenocarcinoma Growth and Differentiation through differential regulation of ?-catenin-E-cadherin-axis
The purpose of this study was to evaluate whether 2-methoxyestradiol (2-ME2), a promising anticancer agent, modulates Barrett�s esophageal adenocarcinoma (BEAC) cell growth and behavior through cellular pathway involving ?-catenin in partnership with E-cadherin, which appears to play a critical role in the induction of antitumor responses in cancer cells. We found that 2-ME2 markedly reduced the BEAC cell proliferation via regulating apoptotic machinery such as Bcl-2 and Bax. It may nullify the aggressive behavior of the cells by reducing the migratory behavior. Expressions of ?-catenin and E-cadherin and binding of these two proteins is activated in a 2-ME2-dependent fashion in Bic-1 cells. Moreover, over expressions of these two proteins may be due to the stabilization of these proteins by 2-ME2. We found that 2-ME2-induced anti-migratory effects are mediated through the ?-catenin -E-cadherin signaling pathways. In view of these results, we determined whether 2-ME2 reduces BEAC tumor growth. Administration of 2-ME2 significantly decreased the growth of BEAC cells xenografted on the flank of nude mice. The evidence presented points out that the impact of 2-ME2 on ?-catenin-orchestrated signal transduction plausibly plays a multi-faceted functional role to inhibit the proliferation and cell migration of 2-ME2 treated malignant cells and it could be a potential candidate in novel treatment strategies for Barrett�s esophageal adenocarcinoma.
Kambhampati, Suman; Banerjee, Snigdha; Dhar, Kakali; Mehta, Smita; Haque, Inamul; Dhar, Gopal; Majumder, Monami; Ray, Gibanananda; Vanveldhuizen, Peter J.; Banerjee, Sushanta K.
Whole Genome Expression Array Profiling Highlights Differences in Mucosal Defense Genes in Barrett's Esophagus and Esophageal Adenocarcinoma
Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.
Nancarrow, Derek J.; Clouston, Andrew D.; Smithers, B. Mark; Gotley, David C.; Drew, Paul A.; Watson, David I.; Tyagi, Sonika; Hayward, Nicholas K.; Whiteman, David C.
The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.
Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3-positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance. PMID:22301112
Roesly, Heather B; Khan, Mohammad R; Chen, Hwu Dau Rw; Hill, Kimberly A; Narendran, Nirushan; Watts, George S; Chen, Xiaoxin; Dvorak, Katerina
Change of HER2 status in metastatic esophageal adenocarcinoma: heterogeneity of the disease? Case report and review of literature.
A case report is presented of a patient diagnosed with esophageal adenocarcinoma with an extremely aggressive clinical course. Discordant expression of HER2 in longitudinally-collected biopsies was noted, with the original biopsy testing negative and a follow up biopsy testing positive. Upon retest of the original biopsy however, heterogeneity of HER2 expression was found among tumor clones across three distinct fields. The patient did not survive long enough to receive chemotherapy with trastuzumab, which has shown efficacy in tumors with HER2 positive expression. Understanding of the biological heterogeneity of HER2 expression in the primary tumor is crucial to detect HER2 positive clones, which may yield improved patient outcomes. PMID:23205313
Niu, Jiaxin; Weber, Jeffrey; Gelbspan, Deborah
Change of HER2 status in metastatic esophageal adenocarcinoma: heterogeneity of the disease? Case report and review of literature
A case report is presented of a patient diagnosed with esophageal adenocarcinoma with an extremely aggressive clinical course. Discordant expression of HER2 in longitudinally-collected biopsies was noted, with the original biopsy testing negative and a follow up biopsy testing positive. Upon retest of the original biopsy however, heterogeneity of HER2 expression was found among tumor clones across three distinct fields. The patient did not survive long enough to receive chemotherapy with trastuzumab, which has shown efficacy in tumors with HER2 positive expression. Understanding of the biological heterogeneity of HER2 expression in the primary tumor is crucial to detect HER2 positive clones, which may yield improved patient outcomes.
Weber, Jeffrey; Gelbspan, Deborah
Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells
Background Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown. Methods Human esophageal adenocarcinoma cells were treated 18 hours with 50�300 ?M deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-?B activity was measured using a Nuclear factor-?B reporter construct and confirmed by Western blot analysis for Nuclear factor-?B p65. Results MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-?B activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-?B activity, also decreased MUC2 transcription. Nuclear factor-?B p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-?B in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-?B activity, whereas inhibitors of MAP kinase had no effect. Conclusion Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-?B transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase.
Wu, JianTao; Gong, Jun; Geng, Juan; Song, YinXue
LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus?
Background��Investigation of the expression of an intestinal stem cell marker in esophageal adenocarcinomas (EAC) with and without Barrett's\\u000a Esophagus (BE), with respect to a cancer stem cell (CSC) hypothesis.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and methods��Expression of a putative intestinal stem cell marker LgR5 was analyzed in esophageal cancer specimen (n = 70: 41 EAC with\\u000a BE, 19 EAC without BE, and n =
Burkhard HA von Rahden; Stefan Kircher; Maria Lazariotou; Christoph Reiber; Luisa Stuermer; Christoph Otto; Christoph T Germer; Martin Grimm
MicroRNA alterations in Barrett's esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: Insights for chemoprevention
Background: Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs) is documented to occur in multiple cancer types including esophageal adencarcinoma (EAC) and its only known precursor, Barrett's esophagus (BE). Recent studies have linked dysregulation of specific miRNAs to histological grade, neoplastic progression and metastatic potential. Materials and Methods: Herein, we present a summary of previously reported dysregulated miRNAs in BE and EAC tissues as well as EAC cell lines and evaluate a cranberry proanthocyanidin rich extract's (C-PAC) ability to modulate miRNA expression patterns of three human EAC cell lines (JHEso-Ad-1, OE33 and OE19). Results: A review of 13 published studies revealed dysregulation of 87 miRNAs in BE and EAC tissues, whereas 52 miRNAs have been reported to be altered in BE or EAC cell lines, with 48% overlap with miRNA changes reported in tissues. We report for the first time C-PAC�induced modulation of five miRNAs in three EAC cell lines resulting in 26 validated gene targets and identification of key signaling pathways including p53, angiogenesis, T-cell activation and apoptosis. Additionally, mutiple cancer related networks were ideintified as modulated by C-PAC utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein Analysis Through Evolutionary Relationships (PANTHER), and MetaCore analysis tools. Conclusions: Study results support the cancer inhibitory potential of C-PAC is in part attributable to C-PAC's ability to modify miRNA profiles within EAC cells. A number of C-PAC�modulated miRNAs have been been identified as dysregulated in BE and EAC. Further insights into miRNA dysregulation and modulation by select cancer preventive agents will support improved targeted interventions in high-risk cohorts.
Kresty, Laura A.; Clarke, Jennifer; Ezell, Kristin; Exum, Amy; Howell, Amy B.; Guettouche, Toumy
... prevention of Barrett esophagus and esophageal adenocarcinoma. Several early-phase clinical trials of molecularly targeted cancer regimens are being conducted through NCI�s Accelerating Clinical ...
Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts.
The occurrence of phenotypic differences between monozygotic (MZ) twins is commonly attributed to environmental factors, assuming that MZ twins have a complete identical genetic make-up. Yet, recently several lines of evidence showed that both genetic and epigenetic factors could have a role in phenotypic discordance after all. A high occurrence of copy number variation (CNV) differences was observed within MZ twin pairs discordant for Parkinson's disease, thereby stressing on the importance of post-zygotic mutations as disease-predisposing events. In this study, the prevalence of discrepant CNVs was analyzed in discordant MZ twins of the Esophageal Atresia (EA) and Congenital Diaphragmatic Hernia (CDH) cohort in the Netherlands. Blood-derived DNA from 11 pairs (7 EA and 4 CDH) was screened using high-resolution SNP arrays. Results showed an identical copy number profile in each twin pair. Mosaic chromosome gain or losses could not be detected either with a detection threshold of 20%. Some of the germ-line structural events demonstrated in five out of eleven twin pairs could function as a susceptible genetic background. For example, the 177-Kb loss of chromosome 10q26 in CDH pair-3 harbors the TCF7L2 gene (Tcf4 protein), which is implicated in the regulation of muscle fiber type development and maturation. In conclusion, discrepant CNVs are not a common cause of twin discordancy in these investigated congenital anomaly cohorts. PMID:22071887
Veenma, Danielle; Brosens, Erwin; de Jong, Elisabeth; van de Ven, Cees; Meeussen, Connie; Cohen-Overbeek, Titia; Boter, Marjan; Eussen, Hubertus; Douben, Hannie; Tibboel, Dick; de Klein, Annelies
Prognostic Value and Targeted Inhibition of Survivin Expression in Esophageal Adenocarcinoma and Cancer-Adjacent Squamous Epithelium
Background Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies.�While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC) and/or cancer-adjacent squamous epithelium (CASE). The purpose of this study was 1) to determine the degree of survivin up regulation in samples of EAC and CASE, 2) to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3) to examine the effect of survivin inhibition on apoptosis in EAC cells. Methods Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs) to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome. Results Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis. Conclusion Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker.
Malhotra, Usha; Zaidi, Ali H.; Kosovec, Juliann E.; Kasi, Pashtoon M.; Komatsu, Yoshihiro; Rotoloni, Christina L.; Davison, Jon M.; R, Clint; Irvin; Hoppo, Toshitaka; Nason, Katie S.; Kelly, Lori A.; Gibson, Michael K.; Jobe, Blair A.
STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett's adenocarcinomas.
Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC, n=49) and Barrett's adenocarcinomas (BAC, n=61) revealed similar STAT3 expression in ESCCs and BACs (P=0.109), but preferentially activated P-STAT3 in ESCCs (P=0.013). In vitro, strong STAT3 activation was seen by epidermal growth factor (EGF) stimulation in OE21 (ESCC) cells, whereas OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 (P=0.0148) and OE33 (P=0.0243) cells. Importantly, STAT3 knockdown reduced cell migration of OE33 cells by 2.5-fold in two types of migration assays (P=0.073, P=0.015), but not in OE21 cells (P=0.1079, P=0.386). Investigation of transcriptome analysis of STAT3 knockdown revealed a reduced STAT3 level associated with significant downregulation of cell cycle genes in both OE21 (P<0.0001) and OE33 (P=0.01) cells. In contrast, genes promoting cell migration (CTHRC1) were markedly upregulated in OE21 cells, whereas a gene linked to tight-junction stabilization and restricted cell motility (SHROOM2) was downregulated in OE21 but upregulated in OE33 cells. This study shows frequent, but distinct, patterns of STAT3 expression and activation in ESCCs and BACs. STAT3 knockdown reduces cell proliferation in ESCC and BAC cells, inhibits migration of BAC cells and may support cell migration of ESCC cells. Thereby, novel STAT3-regulated genes involved in ESCC and BAC cell proliferation and cell migration were identified. Thus, STAT3 may be further exploited as a potential novel therapeutic target, however, by careful distinction between the two histotypes of esophageal cancers. PMID:23912451
Timme, S; Ihde, S; Fichter, C D; Waehle, V; Bogatyreva, L; Atanasov, K; Kohler, I; Sch�pflin, A; Geddert, H; Faller, G; Klimstra, D; Tang, L; Reinheckel, T; Hauschke, D; Busch, H; Boerries, M; Werner, M; Lassmann, S
Cyclooxygenase inhibitors use is associated with reduced risk of esophageal adenocarcinoma in patients with Barrett's esophagus: a meta-analysis.
Background:Esophageal adenocarcinoma (EAC) has high mortality and is increasing in incidence. Barrett's esophagus (BE) increases the risk for EAC. Studies have reported inconsistent findings on the association between use of cyclooxygenase (COX) inhibitors and the risk of neoplastic progression in BE patients. Therefore, we performed a meta-analysis to investigate this association.Methods:A meta-analysis was undertaken among a total of 9 observational studies using fixed- and random-effects models, comprising 5446 participants; 605 had EAC or high-grade dysplasia (HGD).Results:Overall, COX inhibitors use was associated with a reduced risk of EAC/HGD among BE patients (relative risk (RR)=0.64, 95% confidence interval (CI)=0.53-0.77). Aspirin use also reduced the risk of EAC/HGD (RR=0.63, 95% CI=0.43-0.94), as well as non-aspirin COX inhibitors (RR=0.50, 95% CI=0.32-0.78). The chemopreventive effect seemed to be independent of duration response.Conclusions:Cyclooxygenase inhibitors use is associated with a reduced risk of developing EAC in patients with BE. Both low-dose aspirin and non-aspirin COX inhibitors are associated with a reduced risk of neoplasia. More well-designed randomised controlled trials are needed to increase our understanding of the chemopreventive effect of COX inhibitors. PMID:24651385
Zhang, S; Zhang, X-Q; Ding, X-W; Yang, R-K; Huang, S-L; Kastelein, F; Bruno, M; Yu, X-J; Zhou, D; Zou, X-P
Assessment of the Analgesic Effects of Extrapleural Infusion of Ropivacaine in Neonates with Esophageal Atresia (EA) Repair
Insufficient control of post-thoracotomy pain can produce breathing dysfunction and long term staying in neonatal intensive care unit (NICU). It can increase the incidence of pulmonary complications such as atelectasis, pneumonia and respiratory failure. The aim of this study was to determine the analgesic effect of continuous extrapleural nerve block, using ropivacaine, in neonates younger than 7 days old with esophageal atersia (EA) and the incidence of atelectasis and duration of hospitalization in NICU. For this purpose, from February 2007 till January 2009 in Mofid children�s hospital, 68 neonates under 7 days old whom were candidate for thoracotomy due to esophageal atresia were, randomly divided into two groups in a controlled clinical trial. The cases received extrapleural infusion of ropivacaine 0.5% (0.1 mL/kg/h for 48 h) and controls received acetaminophen 20 mg/kg three times a day via the rectal route. Hemodynamically unstable patients and those who suffered from hospital infections were excluded from the study. After the surgery, all patients had spontaneous breathing without endotracheal tube and stable hemodynamic in NICU. Pain level was determined for each neonate, based on the neonatal infant pain scale (NIPS) grading. The incidence of atelectasis in the first 48 h after operation and throughout the NICU staying were also determined. Results showed that there were no significant difference in the mean age, sex proportions and mean weight between the two groups. The mean pain score in the group received ropivacaine (1.9 � 0.7) was significantly less than the control group (5.2 � 0.6) (p < 0.001). Five percent of cases (n = 1) and 100% of the control group (n=20) had pain scores equal or greater than 3 (p < 0.001). The incidence of atelectasis among cases was less than the control group (35% vs. 65% respectively; p = 0.58). Duration of hospitalization in the case group (12 � 5.6 days) had no significant difference from the control group (13.6 � 4.8 days) (p = 0.3) In conclusion, the results showed that continuous extrapleural infusion of ropivacaine reduces the pain noticeably and atelectasis relatively, after thoracotomy in neonates younger than 7 days suffering from EA, compared to the acetaminophen group.
Rouzrokh, Mohsen; Mirkheshti, Alireza; Mirshemirani, Alireza; Sadeghi, Afsaneh; Tavassoli, Azita; Khaleghnejad Tabari, Ahmad
Genetics Home Reference: Esophageal atresia/tracheoesophageal fistula
... OMIM Genetic disorder catalog Conditions > Esophageal atresia/tracheoesophageal fistula (often shortened to EA/TEF ) On this page: ... 2012 What is EA/TEF? Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a condition resulting from abnormal ...
Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.
Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers. PMID:24901722
Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad
Polymorphism at the 3'-UTR of the thymidylate synthase gene: A potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation
Purpose: To test the hypothesis that TS3'UTR polymorphisms predict outcomes in 146 Caucasian patients with esophageal adenocarcinoma treated with preoperative 5-fluorouracil-based chemoradiation. Methods and Materials: DNA was extracted from hematoxylin-and-eosin stained histologic slides of normal esophageal or gastric mucosa sections from paraffin blocks of esophagectomy specimens. Genotypes of the TS3'UTR polymorphism were determined by polymerase chain reaction for a 6-bp insertion. The genotype groups (0bp/0bp, 6bp/0bp, and 6bp/6bp) were compared for clinical features and overall survival, recurrence-free-survival, locoregional control (LRC), and distant metastasis control. Multivariable Cox regression analyses were performed to find independent predictors for the stated outcomes. Results: There was a trend of association between 6bp/6bp genotype and a decreased risk of local regional recurrence (hazards ratio = 0.211, 95% confidence interval = 0.041-1.095, p = 0.06) compared with other genotypes. There was a trend that patients with 6bp/6bp genotype had a higher 3-year probability of LRC compared with patients with the other two genotypes combined (p = 0.07); however, the difference was not statistically significant. Conclusions: The null hypotheses were not rejected in this study, probably owing to small sample size or the single gene examined. Prospective studies with adequate statistical power analyzing a family of genes involved in the 5-fluorouracil metabolism are needed to assess genetic determinants of treatment-related outcomes in esophageal adenocarcinoma.
Liao Zhongxing [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)]. E-mail: email@example.com; Liu Hongji [Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Swisher, Stephen G. [Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Wang Luo [Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Wu, Tsung-Teh [Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Correa, Arlene M. [Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Roth, Jack A. [Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Wei Qingyi [Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma
Introduction The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. Materials and methods Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n?=?173), including paired samples of benign-appearing squamous epithelium (n?=?51), gastric mucosa (n?=?114), Barrett�s esophagus (BE) or intestinal metaplasia (IM) (n?=?57) and lymph node metastases (n?=?75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. Results PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p?0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p?=?0.002) and inversely associated with involved margins (p?=?0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a prolonged OS (HR?=?0.60, 95% CI 0.36-0.99) and RFS (HR?=?0.49, 95% CI 0.27-0.90) in patients with radically resected (R0) primary tumours and of an improved RFS (HR?=?0.32, 95% CI 0.15-0.69) in curatively treated patients with R0 resection/distant metastasis-free disease. Conclusion High PIGR expression independently predicts a decreased risk of recurrence and an improved survival in patients with adenocarcinoma of the upper gastrointestinal tract. These findings are of potential clinical relevance and merit further validation.
Genome-Wide Catalogue of Chromosomal Aberrations in Barrett's Esophagus and Esophageal Adenocarcinoma: a High-Density SNP Array Analysis
To better understand the molecular mechanisms behind esophageal adenocarcinoma (EAC) tumorigenesis, we used high-density single nucleotide polymorphism (SNP) arrays to profile chromosomal aberrations at each of the four sequential progression stages � Barrett�s metaplasia (BM), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC, in 101 patients. We observed a significant trend toward increasing loss of chromosomes with higher progression stage. For BM, LGD, HGD, and EAC, respectively, the average numbers of chromosome arms with loss per sample were 0.30, 3.21, 7.70, and 11.90 (P for trend= 4.82 � 10?7), and the mean percentages of SNPs with allele loss were 0.1%, 1.8%, 6.6%, and 17.2% (P for trend = 2.64 � 10?6). In LGD, loss of 3p14.2 (68.4%) and 16q23.1 (47.4%) was limited to narrow regions within the FHIT (3p14.2) and WWOX (16q23.1) genes, whereas loss of 9p21 (68.4%) occurred in larger regions. A significant increase in the loss of other chromosomal regions was seen in HGD and EAC; loss of 17p (47.6%) was one of the most frequent events in EAC. Many recurrent small regions of chromosomal loss disrupted single genes, including FHIT, WWOX, RUNX1, KIF26B, MGC48628, PDE4D, C20orf133, GMDS, DMD, and PARK2, most of which are common fragile site (CFS) regions in the human genome. But RUNX1 at 21q22 appeared to be a potential tumor suppressor gene in EAC. Amplifications were less frequent than losses and mostly occurred in EAC. The 8q24 (containing Myc) and 8p23.1 (containing CTSB) were the two most frequently amplified regions. In addition, a significant trend toward increasing amplification was associated with higher progression stage.
Gu, Jian; Ajani, Jaffer; Hawk, Ernest; Ye, Yuanqing; Lee, Jeffrey H.; Bhutani, Manoop S.; Hofstetter, Wayne L.; Swisher, Stephen G.; Wang, Kenneth; Wu, Xifeng
Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma Shared Susceptibility Locus in PLCE1: A Meta-Analysis
Background And Objective Two recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). Subsequent case-control studies have reported this association in other populations. However, the findings were controversial and the effect remains undetermined. Our aim is to provide a precise quantification of the association between PLCE1 rs2274223 variation and the risk of ESCC and GCA. Methods Studies were identified by a literature search in MEDLINE and EMBASE databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association in allele, dominant, recessive, homozygous, and heterozygous models. Results Ten articles were identified, including 22156 ESCC cases and 28803 controls, 5197 GCA cases and 17613 controls. Overall, PLCE1 rs2274223 G allele (G vs. A: OR=1.26, 95% CI: 1.15-1.39 for ESCC; OR=1.51, 95% CI: 1.35�1.69 for GCA) and its carrier (GG +AG vs. AA: OR = 1.23; 95% CI =1.02-1.49 for ESCC; OR =1.62; 95% CI =1.15-2.29 for GCA) were significantly associated with the risk of ESCC and GCA. In stratified analysis by ethnicity, significant association of PLCE1 rs2274223 G allele and the risk of ESCC (OR=1.33, 95% CI 1.21�1.45) and GCA (OR =1.56, 95% CI: 1.47-1.64) was observed in Chinese population. Conclusions Our meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population.
Mai, Ruiqin; Cheng, Yabin; Huang, Yuanshen; Zhang, Guohong
Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays.
We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23-208) per tumor. LOH and gains averaged 33 (range, 3-83) and 31 (range, 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7-57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0-11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development. PMID:18519675
Nancarrow, Derek J; Handoko, Herlina Y; Smithers, B Mark; Gotley, David C; Drew, Paul A; Watson, David I; Clouston, Andrew D; Hayward, Nicholas K; Whiteman, David C
The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma
Esophageal adenocarcinoma (EAC) arises in the backdrop of reflux-induced metaplastic phenomenon known as Barrett esophagus. The prognosis of advanced EAC is dismal, and there is an urgent need for identifying molecular targets for therapy. Serial Analysis of Gene Expression (SAGE) was performed on metachronous mucosal biopsies from a patient who underwent progression to EAC during endoscopic surveillance. SAGE confirmed significant upregulation of Axl �tags� during the multistep progression of Barrett esophagus to EAC. In a cohort of 92 surgically resected EACs, Axl overexpression was associated with shortened median survival on both univariate (p < 0.004) and multivariate (p < 0.036) analysis. Genetic knockdown of Axl receptor tyrosine kinase (RTK) function was enabled in two EAC lines (OE33 and JH-EsoAd1) using lentiviral short hairpin RNA (shRNA). Genetic knockdown of Axl in EAC cell lines inhibited invasion, migration and in vivo engraftment, which was accompanied by downregulation in the activity of the Ral GTPase proteins (RalA and RalB). Restoration of Ral activation rescued the transformed phenotype of EAC cell lines, suggesting a novel effector mechanism for Axl in cancer cells. Pharmacological inhibition of Axl was enabled using a small molecule antagonist, R428 (Rigel Pharmaceuticals). Pharmacological inhibition of Axl with R428 in EAC cell lines significantly reduced anchorageindependent growth, invasion and migration. Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2/neu) at the Tyr877 residue, indicative of receptor crosstalk. Axl RTK is an adverse prognostic factor in EAC. The availability of small molecule inhibitors of Axl function provides a tractable strategy for molecular therapy of established EAC.
Alvarez, Hector; Montgomery, Elizabeth A; Karikari, Collins; Canto, Marcia; Dunbar, Kerry B; Wang, Jean S; Feldmann, Georg; Hong, Seung-Mo; Haffner, Michael C; Meeker, Alan K; Holland, Sacha J; Yu, Jiaxin; Heckrodt, Thilo J; Zhang, Jing; Ding, Pingyu; Goff, Dane; Singh, Rajinder; Roa, Juan Carlos; Marimuthu, Arivusudar; Riggins, Gregory J; Eshleman, James R; Nelkin, Barry D; Pandey, Akhilesh
Association of HER2/ErbB2 Expression and Gene Amplification with Pathological Features and Prognosis in Esophageal Adenocarcinomas
Purpose We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression and gene amplification in patients with curatively resected esophageal adenocarcinoma (EAC). Experimental Design HER2 expression was analyzed by immunohistochemistry (IHC) in surgical EAC specimens (n=713). Gene amplification was examined by fluorescence in situ hybridization (FISH) in a large subset (n=344). Most tumors were T3�4 (66%) or node-positive (72%); 95% were located in the esophagus or gastroesophageal junction. No patient received neoadjuvant therapy. Cox models were used. Results Overall, 17% of EACs were HER2-positive (ie, IHC3+ or IHC2+ with amplification), with strong agreement between HER2 amplification (HER2/CEP17 ratio ?2) and expression (?=.83). HER2-positivity was significantly associated with lower tumor grade, less invasiveness, fewer malignant nodes, and the presence of adjacent Barrett�s esophagus (BE). EACs with BE had higher odds of HER2-positivity compared to EACs without BE, independent of pathologic features (odds ratio 1.8 [95% confidence interval (CI) 1.1�2.8], p=.014). Among all cases, HER2-positivity was significantly associated with disease-specific survival (DSS) in a manner that differed by the presence or absence of BE (p for interaction=.0047). In EACs with BE, HER2-positivity was significantly associated with improved DSS (hazard ratio 0.54 [95% CI 0.35�0.84], p=.0065) and overall survival (p=.0022) independent of pathologic features, but was not prognostic among EACs without BE. Conclusions HER2-positivity was demonstrated in 17% of resected EACs and associated with reduced tumor aggressiveness. EACs with BE had nearly twice the odds of being HER2-positive and, within this subgroup, HER2-positivity was independently associated with improved survival.
Yoon, Harry H.; Shi, Qian; Sukov, William R.; Wiktor, Anne E.; Khan, Maliha; Sattler, Christopher A.; Grothey, Axel; Wu, Tsung-Teh; Diasio, Robert B.; Jenkins, Robert B.; Sinicrope, Frank A.
Optimization and expansion of predictive models for Barrett's esophagus and esophageal adenocarcinoma: could a life-course exposure history be beneficial?
Thrift et al. provide preliminary evidence that younger age of symptomatic gastroesophageal reflux disease exposure is associated with increased risk of Barrett's esophagus. If these findings are confirmed in other studies, the next logical steps are to test whether this, and other age-specific exposures, can help optimize predictive models of Barrett's esophagus and progression to esophageal adenocarcinoma. Expansion of these models to the general population and the greater Barrett's esophagus population, respectively, will be required for a screening and surveillance approach to be clinically successful and cost-effective. PMID:23735915
Cook, Michael B
Early Involvement of Death-Associated Protein Kinase Promoter Hypermethylation in the Carcinogenesis of Barrett's Esophageal Adenocarcinoma and Its Association with Clinical Progression1
Esophageal Barrett's adenocarcinoma (BA) develops through a multistage process, which is associated with the transcriptional silencing of tumor-suppressor genes by promoter CpG island hypermethylation. In this study, we explored the promoter hypermethylation and protein expression of proapoptotic deathassociated protein kinase (DAPK) during the multistep Barrett's carcinogenesis cascade. Early BA and paired samples of premalignant lesions of 61 patients were analyzed by methylation-specific polymerase chain reaction and immunohistochemistry. For the association of clinicopathological markers and protein expression, an immunohistochemical tissue microarray analysis of 66 additional BAs of advanced tumor stages was performed. Hypermethylation of DAPK promoter was detected in 20% of normal mucosa, 50% of Barrett's metaplasia, 53% of dysplasia, and 60% of adenocarcinomas, and resulted in a marked decrease in DAPK protein expression (P < .01). The loss of DAPK protein was significantly associated with advanced depth of tumor invasion and advanced tumor stages (P < .001). Moreover, the severity of reflux esophagitis correlated significantly with the hypermethylation rate of the DAPK promoter (P < .003). Thus, we consider DAPK inactivation by promoter hypermethylation as an early event in Barrett's carcinogenesis and suggest that a decreased protein expression of DAPK likely plays a role in the development and progression of BA.
Kuester, Doerthe; Dar, Altaf A; Moskaluk,, Christopher C; Krueger, Sabine; Meyer, Frank; Hartig, Roland; Stolte, Manfred; Malfertheiner, Peter; Lippert, Hans; Roessner, Albert; El-Rifai, Wael; Schneider-Stock, Regine
Hypomethylation of Noncoding DNA Regions and Overexpression of the Long Noncoding RNA, AFAP1-AS1, in Barrett's Esophagus and Esophageal Adenocarcinoma
BACKGROUND & AIMS Alterations in methylation of protein-coding genes are associated with Barrett�s esophagus (BE) and esophageal adenocarcinoma (EAC). Dys-regulation of noncoding RNAs occurs during carcinogen-esis but has never been studied in BE or EAC. We applied high-resolution methylome analysis to identify changes at genomic regions that encode noncoding RNAs in BE and EAC. METHODS We analyzed methylation of 1.8 million CpG sites using massively parallel sequencing-based HELP tagging in matched EAC, BE, and normal esophageal tissues. We also analyzed human EAC (OE33, SKGT4, and FLO-1) and normal (HEEpic) esophageal cells. RESULTS BE and EAC exhibited genome-wide hypomethylation, significantly affecting intragenic and repetitive genomic elements as well as noncoding regions. These methylation changes targeted small and long noncoding regions, discriminating normal from matched BE or EAC tissues. One long noncoding RNA, AFAP1-AS1, was extremely hypomethylated and overexpressed in BE and EAC tissues and EAC cells. Its silencing by small interfering RNA inhibited proliferation and colony-forming ability, induced apoptosis, and reduced EAC cell migration and invasion without altering the expression of its protein-coding counterpart, AFAP1. CONCLUSIONS BE and EAC exhibit reduced methylation that includes noncoding regions. Methylation of the long noncoding RNA AFAP1-AS1 is reduced in BE and EAC, and its expression inhibits cancer-related biologic functions of EAC cells.
Wu, Wenjing; Bhagat, Tushar D.; Yang, Xue; Song, Jee Hoon; Cheng, Yulan; Agarwal, Rachana; Abraham, John M.; Ibrahim, Sariat; Bartenstein, Matthias; Hussain, Zulfiqar; Suzuki, Masako; Yu, Yiting; Chen, Wei; Eng, Charis; Greally, John; Verma, Amit; Meltzer, Stephen J.
Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer
Long-term outcome of esophageal anastomosis.
After repair of esophageal atresia (EA) in a newborn, esophageal dysmotility presenting as dysphagia and symptomatic gastroesophageal reflux are common. Significant esophageal morbidity associated with EA extends into adulthood. In adulthood approximately one-fifth of the patients have developed epithelial metaplastic changes, one-third of these have intestinal metaplasia (Barrett esophagus). Surgical complications, increasing age, and impaired esophageal motility predict the development of epithelial metaplasia after repair of EA. To date, worldwide, eight cases of esophageal cancer have been reported in young adults treated for EA. Incidence of esophageal cancer after EA repair is very much likely to increase in the future. Life-long endoscopic follow-up is warranted in patients with EA. PMID:23737132
Rintala, R J; Pakarinen, M P
Genomic array and expression analysis of frequent high-level amplifications in adenocarcinomas of the gastro-esophageal junction.
Adenocarcinomas of the gastroesophageal junction (GEJ) show frequent high-level amplifications (HLA), but the underlying genes are not well defined. We have characterized genomic gain in 14 GEJ carcinomas by array-based comparative genomic hybridization (aCGH). The most frequent gains and amplifications were detected at 7q (57%), 8q (57%), 17q (64%), and 20q (79%), with minimally amplified regions at 7q21.1, 8q24.2, 17q12, and 20q13.2. Five HLA were detected on 7q, one on 8q, two on 17q, and three on 20q. HLA of 8q24 and 17q12 were related to MYC and ERBB2, respectively. The HLA on 7q21 was associated recurrently with ABCB1, whereas the amplified region on 20q13 implicated ZNF217, BCAS1, and CYP24. RNA expression analysis of 11 adenocarcinomas by reverse-transcription polymerase chain reaction was performed for cancer-related genes residing at 7q21 (ABCB1, ABCB4, CDK6, HGF, DMTF1, SRI, TP53AP1) and 20q13 (ZNF217, BCAS1, CYP24, TNFRSF6B). The most frequently upregulated gene on 7q21 was HGF (45%), but there was no association with genomic amplification. The most frequently overexpressed gene at 20q13 was BCAS1 (27%), which was related to HLA of this region (P = 0.006) in all three cases. We conclude that HLA occur often in GEJ adenocarcinomas. The gene responsible for the HLA of 7q21 requires further investigation, whereas BCAS1 is a good candidate for the frequent amplification of 20q13. PMID:16631473
van Dekken, Herman; Vissers, Kees; Tilanus, Hugo W; Kuo, Wen L; Tanke, Hans J; Rosenberg, Carla; Ijszenga, Marije; Szuhai, Karoly
Phase I and II enzyme polymorphisms as risk factors for Barrett's esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis
SUMMARY Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett�s esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta-analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single-nucleotide polymorphisms (SNPs) examined in ?3 studies were meta-analyzed to obtain a pooled estimate of effect. Meta-analysis suggested the minor allele for GSTP1 Val105 conveys modest excess risk (odds ratio [OR]BE = 1.50, 95% confidence interval [CI] 1.16�1.95; OREAC = 1.20, 95% CI 0.94�1.54). No excess risk was observed with GSTM1 null (ORBE = 0.77, 95% CI: 0.56�1.08; OREAC = 1.08, 95% CI: 0.79�1.48), GSTT1 null (ORBE = 1.35, 95% CI: 0.91�2.01; OREAC = 0.84, 95% CI: 0.48�1.49), or CYP1A Val462 (OREAC = 0.89, 95% CI: 0.40�1.97). Insufficient data existed to meta-analyze remaining SNPs. Our review identified GSTP1Ile105Val as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta-analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non-Caucasians and to evaluate other phase I/II polymorphisms.
Bull, L. M.; White, D. L.; Bray, M.; Nurgalieva, Z.; El-Serag, H. B.
Most of the children operated for esophageal atresia will survive the neonatal period. However, medium-term and late complications are frequent in this population. Gastroesophageal reflux disease is observed in 26 to 75% of the cases and can be responsible for peptic esophagitis, anastomotic stenosis, and Barrett esophagus, which is a risk factor for adenocarcinoma of the esophagus. Dysphagia is frequently observed, sometimes several years after the surgery, affecting up to 45% of children at the age of 5 years. Growth retardation is present in nearly one-third of children at the age of 5 years. Ear, nose, and throat and respiratory complications are also very frequent but tend to improve with time. Tracheomalacia is found in 75% of these children at birth, sometimes responsible for severe complications (malaise, bradycardia). Respiratory symptoms are dominated by chronic cough, wheezing, and infections reported in 29% of the children by the age of 5 years. Restrictive, obstructive syndromes and bronchial hyperactivity can be observed, but usually remain moderate. All these complications can influence the patient's quality of life, which is moderately impaired compared to healthy controls. The high frequency of late sequelae in esophageal atresia justifies regular and multidisciplinary follow-up through adulthood. PMID:22835908
Gottrand, F; Sfeir, R; Thumerelle, C; Gottrand, L; Fayoux, P; Storme, L; Lamblin, M-D; Seguy, D; Michaud, L
Prenatal diagnosis of esophageal atresia
The prenatal sonographic detection of esophageal atresia (EA) has been possible for more than a decade and relies on the finding of a small or absent fetal stomach bubble associated with maternal polyhydramnios. The aims of this study were to assess the accuracy of this technique and to determine whether the outcome of prenatally diagnosed EA differs from its postnatal
Mark D Stringer; Kathleen M McKenna; Ruth B Goldstein; Roy A Filly; N. Scott Adzick; Michael R Harrison
HER-2/neu Gene Amplification in Relation to Expression of HER2 and HER3 Proteins in Patients With Esophageal Adenocarcinoma
BACKGROUND Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors� knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance. METHODS Patients with untreated EACs (N 5 673) were analyzed for HER2 amplification and polysomy 17 by fluorescence in situ hybridization in parallel with immunohistochemistry (IHC) (IHC scores of 0�1+, 2+, and 3+). Amplification was defined as HER2=CEP17 ?2. HER3 expression by IHC was analyzed in randomly selected cases (n 5 224). IHC and fluorescence in situ hybridization results were compared using least squares linear regression. RESULTS Overall, 17% of the EACs (116 of 673 EACs) were HER2-amplified with an amplification frequency that was highest among IHC3+ cases (89%) and declined among IHC2+ cases (13%) and IHCO to IHC1+ cases (4%). Among HER2-amplified cases, the level of amplification increased linearly with HER2 membranous expression (HER2/CEP17 ratio: 7.9 in IHC3+ and 5.5 in IHC2+ vs 2.8 in IHCO to IHC11 [P<.0001]), with 14% of amplified tumors demonstrating absent/faint expression (IHCO to IHC1+). Polysomy 17 was not found to be associated with HER2 expression. Cytoplasmic HER3 expression was detected in 87% of tumors (195 of 224 tumors) and was found to be significantly associated with better differentiation (P<.0001). Stepwise increases in HER3 expression were associated with higher HER2 expression levels (P = .0019). CONCLUSIONS Levels of HER2 protein expression and amplification were found to be linearly associated and highly concordant. Among amplified tumors with absent/faint expression, the level of amplification was low. Frequent expression of HER3 suggests its relevance as a therapeutic target, and its significant association with HER2 supports ongoing efforts to inhibit HER2/HER3 in patients with EAC.
Yoon, Harry H.; Sukov, William R.; Shi, Qian; Sattler, Christopher A.; Wiktor, Anne E.; Diasio, Robert B.; Wu, Tsung-Teh; Jenkins, Robert B.; Sinicrope, Frank A.
Physical Activity and Sedentary Behavior in Relation to Esophageal and Gastric Cancers in the NIH-AARP Cohort
Introduction Body mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). Methods Self-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI) Results During 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR>5 times/week vs. never=0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15�18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR5�6 hrs/day vs. <1 hr=0.57, 95%CI: 0.36, 0.92). There was no evidence that BMI was a confounder or effect modifier of any relationship. After adjustment for multiple testing, none of these results were deemed to be statistically significant at p<0.05. Conclusions We find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior.
Cook, Michael B.; Matthews, Charles E.; Gunja, Munira Z.; Abid, Zaynah; Freedman, Neal D.; Abnet, Christian C.
Overexpression of interleukin-8 receptor 2 (IL-8R2) indicates better prognosis in esophageal adenocarcinoma and squamous cell carcinoma procession.
Researches have showed that interleukin family or receptors play a role in many human tumor progressions including esophageal carcinoma. In this study, we examined the expression of interleukin-8 receptor 2 (IL-8R2) and analyze the relationship between it and esophageal carcinoma clinical characteristics. IL-8R2 protein expression was confirmed by immunohistochemistry and immunofluorescence arrays and was analyzed further via Western blot and qRT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics were evaluated by Mann-Whitney and Kruskal-Wallis test. Via�Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with normal esophageal tissue, IL-8R2 protein was overexpressed significantly in esophageal cancer (p�<�0.05) and was observed both in cytoplasm and nuclear. The lower expression of IL-8R2 protein was observed with higher p staging of esophageal cancer, and the significant association between them was confirmed (p�=�0.000), and in advanced p T stage, the similar result was obtained (p�=�0.015); however, compared with lymph node metastasis-negative group, it is no significant difference in positive group (p�=�0.152). In a Kaplan-Meier analysis, compared with IL-8R2 low expression, IL-8R2 high expression identified a group of patients with the longest OS. Cox proportional hazard models revealed that IL-8R2 predicted long time to OS. The higher expression of IL-8R2 was found in early esophageal carcinoma, which may indicate that IL-8R2 plays an important role and is better prognostic factor in esophageal cancer development. PMID:24972913
Liang, Bing; Zhao, Hui; Che, Jian-Bo; Wang, Hao-Jie; Shi, Gong-Ning
Management of Barrett's esophageal carcinoma.
Barrett's esophagus (BE) is the premalignant lesion from which esophageal adenocarcinoma near the esophagogastric junction arises. The management of BE and the treatment of Barrett's esophageal adenocarcinoma (BEA) are important clinical issues in Europe and the United States. As the Helicobacter pylori infection rate in Japan is decreasing in the younger population, the incidence of BE and adenocarcinoma arising from BE may start increasing. Thus, we review the current status of BEA and its management. Magnifying endoscopy with narrow-band imaging is important for diagnosing dysplasia arising from BE. In Japan, adenocarcinoma arising from BE is managed the same way as squamous cell carcinoma in the same location. Strategies to prevent BEA may include medication such as non-steroidal anti-inflammatory drugs and proton pump inhibitors, and anti-reflux surgery. Understanding the pathophysiology of BE will help to reduce the incidence of BEA. PMID:23283352
Miyazaki, Tatsuya; Inose, Takanori; Tanaka, Naritaka; Yokobori, Takehiko; Suzuki, Shigemasa; Ozawa, Daigo; Sohda, Makoto; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kuwano, Hiroyuki
Current knowledge on esophageal atresia
Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of EA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for EA and TEF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap EA is still controversial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following EA/TEF repair. The determination of the risk factors for the complicated evolution following EA/TEF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding EA.
Pinheiro, Paulo Fernando Martins; Simoes e Silva, Ana Cristina; Pereira, Regina Maria
What is prostate adenocarcinoma? Prostate adenocarcinoma accounts for 95 percent of all prostate cancers. It starts in the prostate gland and, ... Cancer Society. Who is most likely to have prostate adenocarcinoma? Prostate adenocarcinoma becomes more common in men ...
Epidemiology of esophageal cancer
Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate. It ranks sixth among all cancers in mortality. In retrospective studies of EsC, smoking, hot tea drinking, red meat consumption, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett�s esophagus is clearly recognized as a risk factor for EsC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we investigated the epidemiologic patterns and causes of EsC. Using population based cancer data from the Surveillance, Epidemiology and End Results Program of the United States; we generated the most up-to-date stage distribution and 5-year relative survival by stage at diagnosis for 1998-2009. Special note should be given to the fact that esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is contributing to increasing death rates (20%) among males in the United States. To further explore the mechanism of development of EsC will hopefully decrease the incidence of EsC and improve outcomes.
Zhang, Yuwei
Tracheal Trifurcation Associated With Esophageal Atresia
We report a newborn with esophageal atresia (EA) in whom right tracheal bronchus (TB) and a tracheal diverticulum were identified intra-operatively. The right TB was further confirmed on MRI scan performed post-operatively. Such a tracheal trifurcation associated with EA has not been reported hitherto from Indian subcontinent.
Progression of Barrett's Metaplasia to Adenocarcinoma Is Associated with the Suppression of the Transcriptional Programs of Epidermal Differentiation
We did expressional profiling on 24 paired samples of normal esophageal epithelium, Barrett's metaplasia, and esophageal adenocarcinomas. Matching tissue samples representing the three different histologic types were obtained from each patient undergoing esophagectomy for adenocarcinoma. Our analysis compared the molecular changes accompanying the transformation of normal squamous epithelium with Barrett's esophagus and adenocarcinoma in individual patients rather than in a
Erik T. Kimchi; Mitchell C. Posner; James O. Park; Thomas E. Darga; Masha Kocherginsky; Theodore Karrison; John Hart; Kerrington D. Smith; James J. Mezhir; Ralph R. Weichselbaum; Nikolai N. Khodarev
Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression
A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to\\u000a molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case�control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia\\u000a adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined
Jonine D. Figueroa; Mary Beth Terry; Marilie D. Gammon; Thomas L. Vaughan; Harvey A. Risch; Fang-Fang Zhang; David E. Kleiner; William P. Bennett; Christine L. Howe; Robert Dubrow; Susan T. Mayne; Joseph F. Fraumeni Jr; Wong-Ho Chow
Adjuvant concurrent chemoradiation using intensity-modulated radiotherapy and simultaneous integrated boost for resected high-risk adenocarcinoma of the distal esophagus and gastro-esophageal junction
Purpose Multimodality therapy leads to improved outcomes for adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) over surgery alone. At our institution, adjuvant chemoradiation (chemoRT) using IMRT and SIB is standard of care for resected high-risk disease. In this study, we review our experience with a recent cohort of patients treated in this manner. Methods and materials We identified 18 patients with resected T3 and/or N1 adenocarcinoma of the distal esophagus and GEJ who received adjuvant chemoRT. A large elective volume (PTV1) and a smaller high-risk volume (PTV2) were irradiated simultaneously using IMRT and an SIB technique. All patients received concurrent chemotherapy. Relevant clinical outcomes are reported. Results The median dose to 95% of PTV1 was 3747cGy and to 95% of PTV2 was 4876cGy. All RT was given in a median of 28 daily fractions. Four patients did not complete chemotherapy. At a median follow up of 952 days from the start of RT, 7 of 18 patients were dead; of these, 3 had developed local recurrence only; 3 had developed both local and distant recurrence; 1 died of a late toxicity, without recurrence. OS was 88% at 1year, 76% at 2 years and 58% at 3 years. Freedom from local recurrence was 88% at 1 year, 82% at 2 years and 82% at 3 years. Freedom from distant recurrence was 72% at 1 year, 67% at 2 years and 56% at 3 years. Toxicity was acceptable. Conclusions Adjuvant concurrent chemoRT with IMRT and SIB is feasible for resected high-risk adenocarcinoma of the distal esophagus and GEJ. Our results describe how modern treatment techniques can be employed as part of a treatment paradigm that is neither commonly used nor commonly described in the literature.
Complete and Sustained Objective Response per RECIST to Irvalec (PM02734) in Undifferentiated Large Cell Esophageal Adenocarcinoma: A Case Report and a Review of the Literature
Undifferentiated large cell carcinoma is a rare entity in esophageal cancer and very few data are available in the literature on this uncommon histological subtype. We report a case of a 58-year-old Caucasian male previously treated with cisplatin/5-fluorouracil, docetaxel and carboplatin/plitidepsin who received treatment with a novel antitumor agent, Irvalec (PM02734), as fourth line. The patient received treatment from July 2006 to July 2009, a total of 49 cycles, at a dose of 2.4 mg/m2 as a 24-hour infusion every 3 weeks. He did not present severe complications or unplanned or cumulative toxicities. Complete and durable response according to RECIST was reported. He was alive at the last follow-up on March 2012.
Salazar, Ramon; Cuadra, Carmen; Gil-Martin, Marta; Vandermeeren, Andrea; Alfaro, Vicente; Coronado, Cinthya
Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population.
The DNA repair pathways help to maintain genomic integrity and therefore genetic variation in the pathways could affect the propensity to develop cancer. Selected germline single nucleotide polymorphisms (SNPs) in the pathways have been associated with esophageal cancer and gastric cancer (GC) but few studies have comprehensively examined the pathway genes. We aimed to investigate associations between DNA repair pathway genes and risk of esophageal squamous cell carcinoma (ESCC) and GC, using data from a genome-wide association study in a Han Chinese population where ESCC and GC are the predominant cancers. In sum, 1942 ESCC cases, 1758 GC cases and 2111 controls from the Shanxi Upper Gastrointestinal Cancer Genetics Project (discovery set) and the Linxian Nutrition Intervention Trials (replication set) were genotyped for 1675 SNPs in 170 DNA repair-related genes. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-level associations were determined using the resampling-based adaptive rank-truncated product approach. The DNA repair pathways overall were significantly associated with risk of ESCC (P = 6.37 � 10(-4)), but not with GC (P = 0.20). The most significant gene in ESCC was CHEK2 (P = 2.00 � 10(-6)) and in GC was CLK2 (P = 3.02 � 10(-4)). We observed several other genes significantly associated with either ESCC (SMUG1, TDG, TP53, GTF2H3, FEN1, POLQ, HEL308, RAD54B, MPG, FANCE and BRCA1) or GC risk (MRE11A, RAD54L and POLE) (P < 0.05). We provide evidence for an association between specific genes in the DNA repair pathways and the risk of ESCC and GC. Further studies are warranted to validate these associations and to investigate underlying mechanisms. PMID:23504502
Li, Wen-Qing; Hu, Nan; Hyland, Paula L; Gao, Ying; Wang, Zhao-Ming; Yu, Kai; Su, Hua; Wang, Chao-Yu; Wang, Le-Min; Chanock, Stephen J; Burdett, Laurie; Ding, Ti; Qiao, You-Lin; Fan, Jin-Hu; Wang, Yuan; Xu, Yi; Shi, Jian-Xin; Gu, Fangyi; Wheeler, William; Xiong, Xiao-Qin; Giffen, Carol; Tucker, Margaret A; Dawsey, Sanford M; Freedman, Neal D; Abnet, Christian C; Goldstein, Alisa M; Taylor, Philip R
No role for glutathione S-transferase genotypes in Caucasian esophageal squamous cell or adenocarcinoma etiology: an European case-control study
Background Identifying and monitoring high-risk patients can aid the prevention of esophageal cancer (EC). The interaction of environmental risk factor exposure and genetic susceptibility may contribute to the etiology of EC. Biotransformation enzymes such as Glutathione S-Transferases (GSTs ) detoxify mutagenic and genotoxic compounds and therefore control the rate of detoxification of carcinogens. Functional polymorphisms in the genes coding for GSTs alter their enzyme activity in vitro, and were reported to modify EC risk in Asians. We hypothesized that altered enzyme activity GST genotypes influence the susceptibility for esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) in Caucasians. Methods We performed a case�control study including 440 Caucasian patients with EC and 592 healthy Caucasian controls matched for age and sex. Functional polymorphisms were selected and genotypes were determined in GST classes Alpha, Mu, Theta and Pi by means of polymerase chain reaction. Genotypes were classified into predicted high, intermediate and low enzyme activity categories based on in vitro activity data. The distribution of the activity genotypes were compared between patients with EAC or ESCC, and controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analyses. Gene-gene interactions were tested and for comparison purposes, the predicted low and intermediate activity genotypes were combined. Genotypes with similar risks for EAC or ESCC were combined and analyzed for multiplicative effects. Results Our analyses includes 327 patients with EAC and 106 patients with ESCC. Low or intermediate activity enzyme genotypes for GSTM1, GSTA1, GSTP1 I105V and A114V as well as for GSTT1, did not significantly modify the risk for ESCC or EAC in our Dutch population. Conclusion Functional genotypes in GST genes are not involved in EAC or ESCC susceptibility in Caucasians, in contrast to results on ESCC from Asia or Africa.
l-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma1
Abstract The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P < .001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P < .05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P < .001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1.
Lin, Jules; Raoof, Duna A; Thomas, Dafydd G; Greenson, Joel K; Giordano, Thomas J; Robinson, Gregory S; Bourner, Maureen J; Bauer, Christopher T; Orringer, Mark B; Beer, David G
Chronic Esophageal reflux induces reflux esophagitis, which is a common finding in gastroenterological practice. Reflux esophagitis produce symptoms like pirosis, regurgitation and in some cases respiratory complains resembling asthma or angina-like chest pain. The pathophysiology of this disease is based on a multifactorial origin, which usually results in the chronic evolution of the disease. In recent years, there have appeared new evidences pointing out to alterations in the relaxing mechanisms of the lower esophageal sphincter; however, some patients having reflux esophagitis show normal shincteric pressure. The sweep action of esophageal smooth muscle is a key point for sending back to stomach the eventually refluxed material; it has been demonstrated that this sweeping action is impaired in many patients having reflux esophagitis. Incompetence of lower esophageal sphincter seems to be related a local to neural alteration rather than to smooth muscle functional disturbance. Recent findings stablis a link between local nitric oxide release and relaxation of the lower esophageal sphincter. Esophageal mucosaldisplay an intrinsic resistance to HCL, pepsin, bilis and enzymes deleterious action by a blockade of back-defusion of hydrogen ions contained in the refluxed material. Nevertheless, some other luminal and non-luminal factors are involved in this mucosalprotection. When these intrinsic resistance factors are abated, tisular lesions like ersion, ulcer and Barret's mucosal changes can occur; is of particular interest because its potential malignant evolution. Esophageal reflux usually resolves with medical treatmen, but in some particular cases surgical correction is indicated for improving the antireflux barrier. PMID:7768423
Salas Coll, C A
Columbia study reveals origins of esophageal cancer:
Researchers at Columbia University Medical Center have identified the critical early cellular and molecular events that give rise to a type of esophageal cancer called esophageal adenocarcinoma, the fastest-rising solid tumor in the United States. The findings, published online today in Cancer Cell, challenge conventional wisdom regarding the origin and development of this deadly cancer and its precursor lesion, Barrett�s esophagus, and highlight possible targets for new clinical therapies.
Epidemiologic risk factors for esophageal cancer development.
In retrospective studies of esophageal cancer (EC), cigarettes and hookah smoking, nass use (a chewing tobacco product), opium consumption, hot tea drinking, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett's esophagus is clearly recognized as a risk factor for EC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we review the epidemiologic studies that have investigated the epidemiologic patterns and causes of EC. PMID:22320939
Mao, Wei-Min; Zheng, Wei-Hui; Ling, Zhi-Qiang
Four patients with herpetic esophagitis were examined. In three of them, the presenting symptom was odynophagia. Early in the course of herpetic esophagitis, shallow round and oval ulcers were seen on barium esophagograms. Later, the ulcers filled with fibrinous exudate, forming nodular plaques that projected into the esophageal lumen. Although these findings are diagnostic of esophagitis, they are not specific for a herpes virus infection. The definitive diagnosis must be established by histologic examination, which demonstrates the cytopathic effect of the herpes virus infection within the squamous epithelium.
Shortsleeve, M.J.; Gauvin, G.P.; Gardner, R.C.; Greenberg, M.S.
Culture - esophageal ... where it is placed in a special dish (culture media) and checked daily to see if any ... There is no preparation needed for a culture. For information on how to prepare for the removal of a piece of esophageal tissue, see EGD .
Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure
Background & Aims: Barrett's esophagus (BE) results from chronic, severe gastroesophageal reflux and predisposes to esophageal adenocarcinoma. Cyclooxygenase (COX)-2 is involved in chronic inflammation and epithelial cell growth. We investigated COX-2 expression in BE and esophageal adenocarcinoma to explore a potential relation between COX-2 expression and metaplasia or carcinogenesis. Methods: Endoscopic mucosal biopsy specimens of Barrett's intestinal metaplasia (n =
Vivian N. Shirvani; Rodica Ouatu-Lascar; Baljeet S. Kaur; M. Bishr Omary; George Triadafilopoulos
Late-onset achalasia after esophageal atresia repair.
The development of achalasia in a patient with a history of esophageal atresia (EA) is rare. Here, we report a patient who had undergone surgery for EA at birth and presented achalasia at 30?years of age. He was successfully treated with laparoscopic surgery. PMID:22151015
Marinello, F G; Targarona, E M; Poca, M; Mones, J; Hern�ndez-Ballesteros, C
Long-term results of esophageal atresia: Helsinki experience and review of literature.
Esophageal atresia (EA) affects one in 2,840 newborns, and over half have associated anomalies that typically affect the midline. After EA repair in infancy, gastroesophageal reflux (GER) and esophageal dysmotility and respiratory problems are common. Significant esophageal morbidity associated with EA extends into adulthood. Surgical complications, increasing age, and impaired esophageal motility predict the development of epithelial metaplasia after repair of EA. To date, worldwide, six cases of esophageal cancer have been reported in young adults treated for EA. According to our data, the statistical risk for esophageal cancer is not higher than 500-fold that of the general population. However, the overall cancer incidence among adults with repaired EA does not differ from that of the general population. Adults with repaired EA have had significantly more respiratory symptoms and infections, as well as more asthma and allergies than does the general population. Nearly half the patients have bronchial hyperresponsiveness. Thoracotomy-induced rib fusion and gastroesophageal reflux-associated columnar epithelial metaplasia are the most significant risk factors for the restrictive ventilatory defect that occurs in over half the patients. Over half the patients with repaired EA are likely to develop scoliosis. Risk for scoliosis is 13-fold after repair of EA in relation to that of the general population. Nearly half of the patients have had vertebral anomalies predominating in the cervical spine, and of these, most were vertebral fusions. The natural history of spinal deformities seems, however, rather benign, with spinal surgery rarely indicated. PMID:21960312
Sistonen, Saara J; Pakarinen, Mikko P; Rintala, Risto J
Toll-Like Receptors in Esophageal Cancer
Esophageal squamous cell carcinoma and esophageal adenocarcinoma are cancers of high mortality. EAC develops through Barrett�s esophagus (BE) and columnar dysplasia, preceded by gastro-esophageal reflux disease. The risk of esophageal squamous cell carcinoma is increased by smoking and alcohol consumption. New treatment options for esophageal cancer are desperately needed. Toll-like receptors (TLRs) play a central role in mammalian immunity and cancer. TLRs are activated by microbial components, such as lipopolysaccharide, flagellin, DNA, and RNA, as well as endogenous ligands, including heat-shock proteins and endogenous DNA. This review summarizes the studies on TLRs in esophageal squamous cell carcinoma and EAC. It has been shown that TLRs 1�10 are expressed in the normal esophagus. In esophageal squamous cell carcinoma, TLRs3, 4, 7, and 9 have been studied, showing associations to aggressive disease properties. In BE and EAC, only TLRs4, 5, and 9 have been studied. In the review, we discuss the implications of TLRs in esophageal cancer.
Kauppila, Joonas H.; Selander, Katri S.
Eosinophilic esophagitis (EoE) is an atopic condition of the esophagus that has become increasingly recognized over the last decade. Diagnosis of the disorder is dependent on the patient�s clinical manifestations and histologic findings on esophageal mucosal biopsies. Patients with eosinophilic esophagitis should be referred to both an allergist and gastroenterologist for optimal management, which may include dietary modifications, pharmacologic agents such as corticosteroids, leukotriene modifiers and biologics as well as mechanical dilatation of the esophagus. The epidemiology, pathophysiology, diagnosis, treatment, and prognosis of EoE are discussed in this review.
Esophageal infarction or acute necrotizing esophagitis is a rare condition that has a dramatic endoscopic appearance of a "black esophagus." The esophageal involvement can vary from the distal third to the total esophagus. Excluding corrosive injury and other well-known rare causes of black esophagus, the etiology of this condition is unknown. Ischemia due to hypoperfusion state is thought to play a central role in the pathogenesis. The treatment is supportive with acid suppression and gastrointestinal rest. Mortality is high due to comorbid conditions. PMID:17298765
Hawari, Rami; Pasricha, Pankaj J
Skeletal malformations associated with esophageal atresia: Clinical and experimental studies
Background\\/Purpose: Patients with esophageal atresia (EA) often have skeletal malformations. The purpose of this study is to examine if similar defects occur in rat fetuses prenatally exposed to Adriamycin, a chemical capable of causing EA in these animals.Methods: The charts of 443 babies with EA were reviewed to assess the incidence and nature of these defects in them. Time-mated female
Huimin Xia; Lucia Migliazza; Sandra Montedonico; Jose I. Rodriguez; Juan A. Diez-Pardo; Juan A. Tovar
Histology, anatomy, or geography? Exome sequencing begins to delineate somatic mutational differences in esophageal cancer.
Esophageal carcinoma is composed of squamous cell and adenocarcinoma types, each with geographically distinct incidence. The earliest exome sequences in this disease begin to illuminate the genetic demarcations of these anatomically related cancers. PMID:23071029
Collisson, Eric A; Cho, Raymond J
[Columnar-celled metaplasia and adenocarcinoma of the esophagus in inhabitants of the Leningrad oblast (by the data of esophagogastroduodenoscopy)].
The article presents an analysis of results of 24 384 endoscopic examinations of the upper gastrointestinal tract in population of the Leningrad oblast with symptoms of gastric dyspepsia during the period from 2007 to 2011. The detection of the columnar-celled metaplasia was 1.1%, adenocarcinoma of the esophagus--0.045%. Esophageal adenocarcinoma occurred in 3.95% of cases of the column-celled esophagus. Barrett's esophagus was revealed in males more often than in women (56.5% and 54.5% respectively). The peak incidence of esophageal adenocarcinoma in males was at the age from 46 to 60 years (36.4% of patients), in females--from 61 to 75 years (27.3% of patients). Intestinal metaplasia was detected in 72.7% of cases with esophageal adenocarcinoma: The diagnosis of long and short segment of column-celled esophagus revealed no significant difference in the development of esophageal adenocarcinoma. PMID:23488270
Vasilevski?, D I; Silant'ev, D S; Mikhaleva, K V; Priadko, A S; Filin, A V; Vorob'ev, S L; Mednikov, S N; Luft, A V; Kulagin, V I; Bagnenko, S F
Loss of Annexin 1 Correlates with Early Onset of Tumorigenesis in Esophageal and Prostate Carcinoma
Annexin I protein expression was evaluated in patient-matched longi- tudinal study sets of laser capture microdissected normal, premalignant, and invasive epithelium from human esophageal squamous cell cancer and prostatic adenocarcinoma. In 25 esophageal cases (20 by Western blot and 5 by immunohistochemistry) and 17 prostate cases (3 by Western blot and 14 by immunohistochemistry), both tumor types showed either com-
Cloud P. Paweletz; David K. Ornstein; Mark J. Roth; Verena E. Bichsel; John W. Gillespie; Valerie S. Calvert; Cathy D. Vocke; Stephen M. Hewitt; Paul H. Duray; Judi Herring; Quan-Hong Wang; Nan Hu; W. Marston Linehan; Phillip R. Taylor; Lance A. Liotta; Michael R. Emmert-Buck; Emanuel F. Petricoin
Esophageal dysphagia can arise from a variety of causes such as motility disorders, mechanical and inflammatory diseases. Adequate management includes a detailed history, evaluation with upper endoscopy, barium radiography and manometry. Treatment is usually tailored to the underlying disease process and in some cases, as in inoperable cancer, palliative management may be necessary. PMID:18940638
Lawal, Adeyemi; Shaker, Reza
... in a Pap test or biopsy by the primary care physician. How does a pathologist diagnose cervical adenocarcinoma? ... abnormal Pap test or has other symptoms, the primary care doctor will perform a colposcopy to remove a ...
Understanding Esophageal Dilation
Understanding Esophageal Dilation What is Esophageal Dilation? Esophageal dilation is a procedure that allows your doctor to dilate, or stretch, a narrowed area of your esophagus [swallowing tube]. Doctors ...
Amiloride and guggulsterone suppression of esophageal cancer cell growth in vitro and in nude mouse xenografts
Esophageal adenocarcinoma is increasing in the US and Western countries and frequent gastresophageal reflux or gastresophageal reflux disease carrying gastric acid and bile acid could contribute to esophageal adenocarcinogenesis. This study was designed to detect the expression of gastric acid-inducing gene Na + /H + exchanger-1 (NHE-1) ex vivo and then to explore targeting of NHE-1 expression or activity to control esophageal cancer cell viability in vitro and in nude mouse xenografts. The data showed that NHE-1 was highly expressed in esophageal adenocarcinoma tissues (66 of 101 cases [65.3%], but not in normal esophageal squamous cell epithelium (1 of 26 cases [3.8%]). Knockdown of NHE-1 expression using NHE-1 shRNA or inhibition of NHE-1 activity using the NHE-1 inhibitor amiloride suppressed viability and induced apoptosis in esophageal cancer cells. Molecularly, amiloride inhibited expression of cyclooxygenase-2 and matrix metallopeptidase-9 but not NHE-1 mRNA in esophageal cancer cells. A combination of amiloride and guggulsterone (a natural bile acid receptor inhibitor) showed more than additive effects in suppressing esophageal cancer cell growth in vitro and in nude mouse xenografts. This study suggests that inhibition of NHE-1 expression or activity or combination of amiloride and guggulsterone could be useful in control of esophageal adenocarcinoma.
GUAN, Baoxiang; HOQUE, Ashraful; XU, Xiaochun
Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China
BACKGROUND: Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse. METHODS: 600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first
Ying Gao; Nan Hu; XiaoYou Han; Carol Giffen; Ti Ding; Alisa Goldstein; Philip Taylor
Diagnosis and Recognition of Early Esophageal Neoplasia
Barrett�s esophagus (BE) is the precursor lesion of esophageal adenocarcinoma, a malignancy with increasing incidence in Western countries. Malignant transformation of Barrett�s metaplasia is a multistep process in which intestinal metaplasia progresses through low-grade and high-grade dysplasia into eventually invasive cancer. Several risk factors for the development of BE have been identified. The degree of dysplasia is currently used as
L�szl� Hersz�nyi; Istv�n Pregun; Zsolt Tulassay
Genetic Alterations in Barrett Esophagus and Adenocarcinomas of the Esophagus and Esophagogastric Junction Region
The incidence of esophageal adenocarcinoma has in- creased markedly in the past two decades, but the genetic alterations in this cancer and its precursor, Barrett mucosa, have not been characterized exten- sively. DNA replication errors and allelic losses of chromosomes 17p, 18q, and 5q were studied in 36 resected adenocarcinomas arising in the esophagus and esophagogastric junction, 56 Barrett adenocarci-
Tsung-Teh Wu; Toshiaki Watanabe; Richard Heitmiller; Marianna Zahurak; Arlene A. Forastiere
Esophageal functional impairments in experimental eosinophilic esophagitis
Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease. Despite the increasing diagnosis of EoE globally, the causes of EoE and other esophageal eosinophilic disorders are not clearly understood. EoE pathology includes accumulation of inflammatory cells (e.g., eosinophils, mast cells), characteristic endoscopic features (e.g., furrows, the formation of fine concentric mucosal rings, exudates), and functional impairments (e.g., esophageal stricture, dysmotility). We hypothesized that the esophageal structural pathology and functional impairments of EoE develop as a consequence of the effector functions of the accumulated inflammatory cells. We analyzed eosinophils (anti-major basic protein immunostaining), esophageal stricture (X-ray barium swallowing), and esophageal motility (isometric force) in two established transgenic murine models of EoE (CD2-IL-5 and rtTA-CC10-IL-13) and a novel eosinophil-deficient model (?dblGATA/CD2-IL-5). Herein, we show the following: 1) CD2-IL-5 and doxycycline (DOX)-induced rtTA-CC10-IL-13 mice have chronic eosinophilic and mast cell esophageal inflammation; 2) eosinophilic esophageal inflammation promotes esophageal stricture in both transgenic murine models; 3) the eosinophil-deficient ?dblGATA/CD-2-IL-5 mice were protected from the induction of stricture, whereas the eosinophil-competent CD2-IL-5 mice develop esophageal stricture; 4) esophageal stricture is not reversible in DOX-induced rtTA-CC10-IL-13 mice (8 wk DOX followed by 8 wk no-DOX); and 5) IL-5 transgene-induced (CD2-IL-5) EoE evidences esophageal dysmotility (relaxation and contraction) that is independent of the eosinophilic esophageal inflammation: CD2-IL-5 and ?dblGATA/CD2-IL-5 mice have comparable esophageal dysmotility. Collectively, our present study directly implicates chronic eosinophilic inflammation in the development of the esophageal structural impairments of experimental EoE.
Mavi, Parm; Rajavelu, Priya; Rayapudi, Madhavi; Paul, Richard J.
Glycomic Expression in Esophageal Disease
Glycosylation is among the most common post translation modifications of proteins in humans. Decades of research have demonstrated that aberrant glycosylation can lead to malignant degeneration. Glycoproteomic studies in the past several years have identified techniques that can successfully characterize a glycan or glycan profile associated with a high-grade dysplastic or malignant state. This review summarizes the current glycomic and glycoproteomic literature with specific reference to esophageal cancer. Esophageal adenocarcinoma represents a highly morbid and mortal cancer with a defined progression from metaplasia (Barrett's esophagus) to dysplasia to neoplasia. This disease is highlighted because (1) differences in glycan profiles between the stages of disease progression have been described in the glycoproteomic literature; (2) a glycan biomarker that identifies a given stage may be used as a predictor of disease progression and thus may have significant influence over clinical management; and (3) the differences in glycan profiles between disease and disease-free states in esophageal cancer are more dramatic than in other cancers.
Mohanty, Sanjay; Tsiouris, Athanasios; Hammoud, Zane
Physical Activity and Esophageal and Gastric Carcinoma in a Large Prospective Study
Background Few studies have investigated the relationship of physical activity to esophageal and gastric carcinoma according to histology and anatomic site. Methods This study prospectively investigated the association between physical activity and esophageal and gastric carcinoma in a cohort of 487,732 U.S. men and women, followed from 1995�1996 to December 31, 2003. All analyses were performed in 2007� 2008. Results During 8 years of follow-up study, 523 cases of esophageal carcinoma (149 squamous cell and 374 adenocarcinoma) and 642 cases of gastric carcinoma (313 cardia and 329 noncardia) were documented. Physical activity was associated with reduced risk of esophageal and gastric adenocarcinomas but was unrelated to esophageal squamous cell carcinoma. The inverse association with physical activity was strongest for gastric noncardia adenocarcinoma (multivariate relative risk [RR] for highest versus lowest physical activity level=0.62, 95% CI=0.44, 0.87). Relationships were weaker but evident for gastric cardia adenocarcinoma (RR=0.83; 95% CI=0.58, 1.19) and esophageal adenocarcinoma (RR=0.75; 95% CI=0.53, 1.06). No significant relationship with physical activity was observed for esophageal squamous cell carcinoma (RR=1.05; 95% CI=0.64, 1.74). Exclusion of cases diagnosed during the first 2 follow-up years did not change those estimates, indicating that the findings are not due to decreased activity levels among participants with undiagnosed cancer at entry. Conclusions Physical activity may play a role in the prevention of upper gastrointestinal tract adenocarcinomas. No association was seen between physical activity and esophageal squamous cell carcinoma.
Leitzmann, Michael F.; Koebnick, Corinna; Freedman, Neal D.; Park, Yikyung; Ballard-Barbash, Rachel; Hollenbeck, Albert; Schatzkin, Arthur; Abnet, Christian C.
Inhibition of Farnesoid X Receptor Controls Esophageal Cancer Cell Growth In Vitro and in Nude Mouse Xenografts
BACKGROUND Gastroesophageal reflux is a risk factor for esophageal adenocarcinoma and bile acid and its farnesoid X receptor (FXR) have been implicated in esophageal tumorigenesis. We investigated the role of FXR expression and activity in esophageal cancer initiation and growth. METHODS FXR expression in esophageal adenocarcinoma tissues was assessed by immunohistochemistry. Knockdown of FXR expression in esophageal cancer cells in vitro and in nude mice xenografts was suppressed by FXR shRNA and guggulsterone (a natural FXR inhibitor). Esophageal cancer cells were treated with bile acids to show their effects on growth-promoting genes. RESULTS FXR was expressed in 48 of 59 esophageal adenocarcinoma tissues (81.3%), and this overexpression was associated with higher tumor grade, greater tumor size, and lymph node metastasis, but was inversely associated with RAR-?2 expression. Knockdown of FXR expression suppressed tumor cell growth in vitro and in nude mouse xenografts. Guggulsterone reduced viability of esophageal cancer cells in a time- and dose-dependent manner, whereas this effect was diminished after knockdown of FXR expression. Guggulsterone induced apoptosis through activation of caspases-8, -9, and -3 in tumor cells. FXR mediated bile acid�induced alterations of gene expression, e.g., RAR-?2 and COX-2. CONCLUSION Inhibition of FXR by FXR shRNA or guggulsterone suppressed tumor cell viability and induced apoptosis in vitro and reduced tumor formation and growth in nude mouse xenografts. FXR mediated bile acid�induced alterations of cell growth-related genes in esophageal cancer cells.
Guan, Baoxiang; Li, Hao; Yang, Zhengduo; Hoque, Ashraful; Xu, Xiaochun
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
Pathological validity of esophageal endoscopy. How real is what we see? Myth or reality?
The purpose of this study was to characterize the spectrum of esophageal pathology at a provincial tertiary care hospital and to evaluate these findings with their respective endoscopic diagnoses. The pathology slides of 183 esophageal biopsies for the year 2000 were reviewed and classified as esophagitis, intestinal metaplasia, low or high grade dysplasia, adenocarcinoma, squamous cell carcinoma or normal. One hundred and fifteen cases (63%) had complete concordant results with respective endoscopic reports. Sixty-eight cases (37%) had discordant results with inaccurate recognition of Barrett's esophagus in 9% and of esophagitis with a false positive in 16% and false negative in 7%. Although esophagoscopy remains a primary investigative tool in gastroesophageal diseases, evaluation of erythema, inflammation and esophagitis can be misleading. Pathologically confirmed esophagitis can occur in a 'normal' esophagus. Accurate endoscopic recognition of short-segment Barrett's remains a diagnostic challenge. PMID:15569367
Kanthan, R; Torkian, B; Kanthan, S C
EPHX1 polymorphisms do not modify esophageal carcinoma susceptibility in Dutch Caucasians.
Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Crucial risk factors are exposure to toxins or carcinogens. Microsomal epoxide hydrolase (mEH) is a biotransformation enzyme essential for the detoxification of xenobiotics. Polymorphisms in exon 3 and exon 4 of the microsomal epoxide hydrolase gene (EPHX1) modify catalytic activity of this enzyme and subsequently may play a role in EC etiology. This case-control study investigated whether these polymorphisms in the EPHX1 gene influence esophageal cancer susceptibility in a Dutch Caucasian population. A case-control study including 349 Caucasian EC patients and 581 Caucasian healthy controls was conducted and the polymorphisms Tyr113His (exon 3) and His139Arg (exon 4) in the EPHX1 gene were determined, using polymerase chain reaction. The distribution of exon 3 and exon 4 genotypes were compared between cases and controls. Analyses included a stratification according to tumor histology; esophageal adenocarcinoma (EAC) or squamous cell carcinoma (ESCC). Furthermore, on the basis of allelic in vitro enzyme activity assays, exon 3 and 4 genotypes were combined and categorized according to their predicted high, medium or low enzyme activity. Homozygosity and heterozygosity for both exon 3 and 4 polymorphisms were correlated with a decreased esophageal squamous cell carcinoma risk. Heterozygosity and homozygosity for both polymorphisms correlated with an increased and a decreased esophageal adenocarcinoma risk, respectively. Predicted intermediate and high activity genotypes were risk and protective factors for esophageal squamous cell carcinoma and esophageal adenocarcinoma, respectively. However, none of these associations were statistically significant. In conclusion, the polymorphisms in exon 3 and exon 4 of the EPHX1 gene do not seem to be modifiers of esophageal squamous cell carcinoma or esophageal adenocarcinoma risk in Dutch Caucasians. PMID:22447130
Dura, Polat; Bregitha, Caro V V; Te Morsche, Rene H M; Roelofs, Hennie M J; Kristinsson, Jon O; Wobbes, Theo; Witteman, Ben J M; Tan, Adriaan C I T L; Drenth, Joost P H; Peters, Wilbert H M
... the disease is found and treated at an early stage . There is no standard or routine screening test for esophageal cancer. Screening for esophageal cancer is under study with screening clinical trials taking place in many parts of the ...
Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin
AIM: To determine the effects of curcumin, (-)-epigallocatechin-3-gallate (EGCG), lovastatin, and their combinations on inhibition of esophageal cancer. METHODS: Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin, EGCG and lovastatin treatment. Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines, tumor xenografts and human esophageal cancer tissues, respectively. RESULTS: These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro. Molecularly, these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2), c-Jun and cyclooxygenase-2 (COX-2), but activated caspase 3 in esophageal cancer cells. The nude mouse xenograft assay showed that EGCG and the combinations of curcumin, EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67, phosphorylated Erk1/2 and COX-2. The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry. The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein. In particular, phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma, while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma. CONCLUSION: The combinations of curcumin, EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts, these drugs also inhibited phosphorylated Erk1/2, c-Jun and COX-2 expression.
Ye, Fei; Zhang, Gui-Hong; Guan, Bao-Xiang; Xu, Xiao-Chun
Evaluation of esophageal diseases.
The diagnosis of esophageal disease can be made by history alone in 80 percent of patients. Primary symptoms include dysphagia, odynophagia, heartburn and central chest pain. Although these symptoms may overlap, one esophageal symptom often predominates. This observation and an understanding of the available diagnostic tests enable the clinician to develop an algorithmic approach to the diagnosis of esophageal diseases. PMID:3942041
Dabaghi, R E; Scott, L D
Esophageal disease in pediatrics
The following on esophageal disease in pediatrics contains commentaries on acquisition of neuromuscular maturation; physiology of esophageal peristaltic and sphincteric reflexes; implications for clinical practice; and conditions that predispose to severe gastroesophageal reflux disease (GERD) in children with potential risk for esophageal cancer.
Jadcherla, Sudarshan R.; Nurko, Samuel
Current management of esophageal cancer
Management of esophageal cancer has evolved since the two last decades. Esophagectomy remains the primary treatment for early stage esophageal cancer although its specific role in superficial cancers is still under debate since the development of endoscopic mucosal treatment. To date, there is strong evidence to consider that locally advanced cancers should be recommended for a multimodal treatment with a neoadjuvant chemotherapy or a combined chemoradiotherapy (CRT) followed by surgery. For locally advanced squamous cell carcinoma or for a part of adenocarcinoma, some centers have proposed treating with definitive CRT to avoid related-mortality of surgery. In case of persistent or recurrent disease, a salvage esophagectomy remains a possible option but this procedure is associated with higher levels of perioperative morbidity and mortality. Despite the debate over what constitutes the best surgical approach (transthoracic versus transhiatal), the current question is if a minimally procedure could reduce the periopertive morbidity and mortality without jeopardizing the oncological results of surgery. Since the last decade, minimally invasive esophagectomy (MIE) or hybrid operations are being done in up to 30% of procedures internationally. There are some consistent data that MIE could decrease the incidence of the respiratory complications and decrease the length of hospital-stay. Nowadays, oncologic outcomes appear equivalent between open and minimally invasive procedures but numerous phase III trials are ongoing.
Thomas, Pascal Alexandre
Robotic benign esophageal procedures.
Robotic master-slave devices can assist surgeons to perform minimally invasive esophageal operations with approaches that have already been demonstrated using laparoscopy and thoracoscopy. Robotic-assisted surgery for benign esophageal disease is described for the treatment of achalasia, epiphrenic diverticula, refractory reflux, paraesophageal hernias, duplication cysts, and benign esophageal masses, such as leiomyomas. Indications and contraindications for robotic surgery in benign esophageal disease should closely approximate the indications for laparoscopic and thoracoscopic procedures. Given the early application of the technology and paucity of clinical evidence, there are currently no procedures for which robotic esophageal surgery is the clinically proven preferred approach. PMID:24780427
Hanna, Jennifer M; Onaitis, Mark W
Neoadjuvant treatment for esophageal squamous cell carcinoma
Squamous cell carcinoma and adenocarcinoma are types of esophageal cancer, one of the most aggressive malignant diseases. Since both histological types present entirely different diseases with different epidemiology, pathogenesis and tumor biology, separate therapeutic strategies should be developed against each type. While surgical resection remains the dominant therapeutic intervention for patients with operable esophageal squamous cell carcinoma (ESCC), alternative strategies are actively sought to reduce the frequency of post-operative local or distant disease recurrence. Such strategies are particularly sought in the preoperative setting. Currently, the optimal management of resectable ESCC differs widely between Western and Asian countries (such as Japan). While Western countries focus on neoadjuvant or definitive chemoradiotherapy, neoadjuvant chemotherapy followed by surgery is the standard treatment in Japan. Importantly, each country and region has established its own therapeutic strategy from the results of local randomized control trials. This review discusses the current knowledge, available data and information regarding neoadjuvant treatment for operable ESCC.
Baba, Yoshifumi; Watanabe, Masayuki; Yoshida, Naoya; Baba, Hideo
Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction
Esophageal adenocarcinoma develops in response to severe gastroesophageal reflux disease through the precursor lesion Barrett esophagus, in which the normal squamous epithelium is replaced by a columnar lining. The incidence of esophageal adenocarcinoma in the United States has increased by over 600% in the past 40 years and the overall survival rate remains less than 20% in the community. This review highlights some of the signaling pathways for which there is some evidence of a role in the development of esophageal adenocarcinoma. An increasingly detailed understanding of the biology of this cancer has emerged recently, revealing that in addition to the well-recognized alterations in single genes such as p53, p16, APC, and telomerase, there are interactions between the components of the reflux fluid, the homeobox gene Cdx2, and the Wnt, Notch, and Hedgehog signaling pathways.
Clemons, Nicholas J; Phillips, Wayne A; Lord, Reginald V
Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines
Purpose: Paclitaxel is a highly effective chemotherapy agent against adenocarcinomas and squamous cell carcinomas of the esophagus.\\u000a However, its precise effects in human esophageal cancer cells are not well understood. This study was designed to examine\\u000a the relationship between cell-cycle phases of paclitaxel-activated checkpoints and to elucidate the molecular pathway of the\\u000a effect of paclitaxel in human esophageal squamous cell
Ahmad Faried; Leri S. Faried; Hitoshi Kimura; Makoto Sohda; Masanobu Nakajima; Tatsuya Miyazaki; Hiroyuki Kato; Tatsuya Kanuma; Hiroyuki Kuwano
High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death
Background High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma. Material and methods Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n?=?173). In addition paired samples of normal squamous epithelium (n?=?53), gastric mucosa (n?=?117), Barrett�s esophagus/gastric intestinal metaplasia (n?=?61) and lymph node metastases (n?=?71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS). Results RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS). Conclusion High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation.
Intramural esophageal dissection associated with esophageal perforation.
Intramural esophageal dissection (IED) is a rare clinical entity involving a mucosal injury and creation of a true and false lumen within the esophagus. We report on a case of IED caused by repeated vomiting due to a small bowel obstruction associated with a small amount of pneumomediastinum on CT. IED has traditionally been believed not to be associated with esophageal perforation. Our case adds to the few reported instances where IED has been associated with extraluminal air leakage, the mildest form of esophageal perforation and demonstrates imaging not previously published in the radiology literature. Our case was successfully managed conservatively. PMID:23819141
Monu, Nicholas C; Murphy, Brian L
[The detection rate of the esophageaL GERD complications among residents of the Leningrad Region (according to the data of esophagogastroduodenoscopy tests)].
This article presents the analysis of 24384 endoscopic investigations of the upper gastrointestinal tract in population of Leningrad region with symptoms of dyspepsia during the period 2007-2011.The results revealed erosive esophagitis in 5.4%, peptic strictures of the esophagus--0.2%, the columnar-lining esophagus (Barrett's esophagus)--1.1%, and esophageal adenocarcinoma--0.045%. This data shows a high prevalence of esophageal complications of GERD in a local population of Russians. PMID:24501940
Vasilevski?, D I; Silant'ev, D S; Mikhaleva, K V; Filin, A V; Vorob'ev, S L; Mednikov, S N; Luft, A V; Kulagin, V I; Bagnenko, S F
Eosinophilic esophagitis: case report.
Eosinophilic esophagitis is an inflammatory condition of the esophagus characterized by eosinophilic infiltration. It is a condition mainly affecting children; the adult form has only recently gained recognition as a distinct entity. The major symptom among adults with eosinophilic esophagitis is dysphagia. It is often misdiagnosed as gastroesophageal reflux disease because of the similarity in symptoms. An endoscopic biopsy is required to distinguish between the conditions. The cause of eosinophilic esophagitis is poorly understood, but food allergy has been implicated. Topical steroids are the most effective and convenient method for the treatment of eosinophilic esophagitis in adults. The long-term prognosis of eosinophilic esophagitis is uncertain; however, data suggests a benign course. We herein present two eosinophilic esophagitis cases that were the first to be diagnosed in our clinic. PMID:17602357
Mungan, Zeynel; Pinarba?i, Binnur; Kaymako?lu, Sabahattin
Esophageal squamous carcinoma in five patients with Barrett's esophagus.
Adenocarcinoma of the esophagus is a well-known complication of Barrett's esophagus. This report describes five patients (three men and two women) with Barrett's esophagus and squamous carcinoma of the esophagus. All patients had hiatal hernia, and three had a history of tobacco and alcohol use. The tumors were located in the Barrett's mucosa in one case, at the squamocolumnar junction in two cases, and in the squamous-lined mucosa above the Barrett's mucosa in two cases. One patient also had focal adenocarcinoma associated with the squamous carcinoma of the esophagus. Review of the literature identified 11 previously reported cases. Occurrence of esophageal squamous carcinoma in Barrett's esophagus patients suggests a possible relationship between these two conditions, and the need for a careful evaluation of the squamous esophageal mucosa and the squamocolumnar junction at the time of endoscopy. PMID:1590313
Paraf, F; Fl�jou, J F; Potet, F; Molas, G; F�k�t�, F
Intramural ganglion structures in esophageal atresia: a morphologic and immunohistochemical study.
Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E), and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF. PMID:20041008
Zuccarello, Biagio; Spada, Antonella; Turiaco, Nunzio; Villari, Daniela; Parisi, Saveria; Francica, Isabella; Fazzari, Carmine; Pederiva, Federica; Tovar, Juan A
Recurrent Spontaneous Esophageal Dissection
Introduction: Spontaneous esophageal dissection is a rare disorder of the esophagus. Case Description: We present what is believed to be the first reported case of recurrent esophageal dissection in a previously healthy 33-year-old man with chronic eosinophilic esophagitis. He had two episodes of spontaneous dissection of the midesophagus separated by a 5-month interval. Both episodes responded to treatment with endoscopic intervention. He has remained free of additional recurrences after definitive endoscopic therapy and oral steroid therapy. A complete description of the case, relevant radiologic imaging, and a review of the relevant literature are provided. Discussion: Endoscopic therapy is an option for the management of recurrent esophageal dissection.
Stephens, Nicholas A.; Walker, Peter A.; Jayanty, Vikram; Raijman, Isaac; Khalil, Kamal
L-Type Amino Acid Transporter1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma1
The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA micro- arrays, overexpression of LAT-1 was found in 87.5% (7\\/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dys- plasia) and was confirmed in 100% (28\\/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5%
Jules Lin; Duna A. Raoof; Dafydd G. Thomas; Joel K. Greenson; Thomas J. Giordano; Gregory S. Robinson; Maureen J. Bourner; Christopher T. Bauer; Mark B. Orringer; David G. Beer
Meat consumption and risk of esophageal and gastric cancer in a large prospective study
Background Red and processed meats could increase cancer risk via several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied. Methods We estimated hazards ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During approximately 10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas and 501 gastric non-cardia adenocarcinomas. Results Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile = 1.79, 95% CI: 1.07�3.01, P for trend = 0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR = 1.44, 95% CI: 1.01�2.07, P for trend = 0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR = 1.35, 95% CI: 0.97�1.89, P for trend = 0.022; HR = 1.45, 95% CI: 0.99�2.12, P for trend = 0.463; HR = 1.47, 95% CI: 0.99-2.20, P for trend = 0.063, respectively). Benzo[a]pyrene, nitrate and nitrite were not associated with esophageal or gastric cancer. Conclusions We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer.
Cross, Amanda J.; Freedman, Neal D.; Ren, Jiansong; Ward, Mary H.; Hollenbeck, Albert R.; Schatzkin, Arthur; Sinha, Rashmi; Abnet, Christian C.
Stomach and esophageal cancers are close in anatomical location and have been combined into one project within TCGA. Although they are two separate cancer types, TCGA is collecting samples from various anatomic subsites along the esophageal and gastric tracts for analysis.
Drug-induced esophagitis is being recognized increasingly in the past few years. Since 1970 more than 650 cases have been reported worldwide caused by 30 or more medications. We have reviewed these cases with a view to classifying this disease based on underlying pathological mechanism. Drug-induced esophageal injury tends to occur at the anatomical site of narrowing, with the middle third behind the left atrium predominating (75.6%). The disease is broadly classified into two groups. The first group being transient and self-limiting as exemplified by the tetracycline group induced injury (65.8%). The second is the persistent esophagitis group, often with stricture, with two distinct entities: (i) patients on nonsteroidal anti-inflammatory agents whose injury is aggravated by gastroesophageal reflux (21.8%) (reflux aggravated); and (ii) patients with potasium chloride and quinidine sulphate induced injury (12.4%) (persistent drug injury). Severe esophageal injury has been reported in some women taking biphosphonates as treatment for postmenopausal osteoporosis. Endoscopic findings in such patients with esophageal injury generally suggested a chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Most cases of medication-induced esophageal injury heal without intervention within a few days. Thus, the most important aspect of therapy is to make the correct diagnosis and then to avoid reinjury with the drug. When possible, potentially caustic oral medications should be discontinued. PMID:19392845
Zografos, G N; Georgiadou, D; Thomas, D; Kaltsas, G; Digalakis, M
Brain metastasis from esophageal carcinoma.
Esophageal carcinoma rarely metastasizes to brain. In our center, among 504 cases of esophageal cancer registered for treatment during a 15-year (1990-2005) period, brain metastasis from esophageal carcinoma was detected in only 1 case. An unusual case of esophageal carcinoma that presented with brain metastasis is reported here. PMID:19542674
Agrawal, Rashi; Shukla, Prity; Shukla, Vikas; Chauhan, Arvind
Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome
Thirty-nine patients with endometrioid adenocarcinoma (EA) and atypical hyperplasia (AH) of the endometrium who received conservative treatment to preserve fertility were collected from member institutions of the Japan Gynecologic Oncology Study Group. Twenty-nine and ten were originally diagnosed with EA without myometrial invasion and AH, respectively. We performed a central pathological review to make definite diagnoses, and the diagnosis of
Tsunehisa Kaku; Hiroyuki Yoshikawa; Hitoshi Tsuda; Atsuhiko Sakamoto; Masaharu Fukunaga; Yoshinori Kuwabara; Masaki Hataeg; Shoji Kodama; Kazuo Kuzuya; Shinji Sato; Toshinobu Nishimura; Masamichi Hiura; Hitoo Nakano; Tsuyoshi Iwasaka; Koji Miyazaki; Toshiharu Kamura
CDX2 hox gene product in a rat model of esophageal cancer
Background Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis. Methods The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10�30 weeks; Group C: >30 weeks). Results No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001). Conclusion De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.
Loss of Heterozygosity Involves Multiple Tumor Suppressor Genes in Human Esophageal Cancers 1
Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppres- sor genes. We examined 72 esophageal tumors (46 squamous cell car- cinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of
Ying Huang; Robert F. Boynton; Patricia L. Blount; Richard J. Silverstein; Jing Yin; Yi Tong; Timothy K. McDaniel; Carnell Newkirk; James H. Resau; Rajeshwari Sridhara; Brian J. Reid; Stephen J. Meltzer
Esophageal cancer staging: improved accuracy by endoscopic ultrasound of celiac lymph nodes
Background. Clinical staging of esophageal cancer is required for optimal therapy but remains imprecise. Pathologic verification of involved lymph nodes could potentially direct treatment allocation. With the rising incidence of distal and gastroesophageal junction adenocarcinomas, assessment of the celiac axis lymph nodes (CLNs) becomes important because it is a common nodal drainage basin. Endoscopic ultrasound (EUS) permits evaluation of CLNs
Carolyn E Reed; Girish Mishra; Anand V Sahai; Brenda J Hoffman; Robert H Hawes
Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk.
MicroRNAs (miRNA) can act as oncogenes or tumor suppressors and modulate the expression of approximately one third of all human genes. To test the hypothesis that adverse alleles in miRNA-related genes may increase the risk for esophageal cancer, we assessed the associations between esophageal cancer risk and 41 potentially functional single nucleotide polymorphisms (SNP) in 26 miRNA-related genes in a case-control study of 346 Caucasian esophageal cancer patients (85.5% with esophageal adenocarcinoma) and 346 frequency-matched (age, gender, and ethnicity) controls. Seven SNPs were significantly associated with esophageal cancer risk. The most notable finding was that the SNP rs6505162, which is located in the pre-mir423 region, was associated with a per-allele odds ratio of 0.64 [95% confidence interval (95% CI), 0.51-0.80; P for trend < 0.0001]. This association remained significant after we corrected for multiple comparisons. A common haplotype of the GEMIN4 gene was associated with a significantly reduced risk of esophageal cancer (odds ratio, 0.65; 95% CI, 0.42-0.99). We did a combined unfavorable genotype analysis to further evaluate the cumulative effects of the promising (risk associated) SNPs. In comparison with the low-risk group (fewer than three unfavorable genotypes), the medium-risk group (three unfavorable genotypes) had a 2.00-fold (95% CI, 1.31-3.08) increased risk and the high-risk group (more than three unfavorable genotypes) had a 3.14-fold (95% CI, 2.03-4.85) increased risk (P for trend < 0.0001). Results for the risk of esophageal adenocarcinoma were similar to the overall risk results. The present study provides the first evidence that miRNAs may affect esophageal cancer risk in general and that specific genetic variants in miRNA-related genes may affect esophageal cancer risk individually and jointly. PMID:19138993
Ye, Yuanqing; Wang, Kenneth K; Gu, Jian; Yang, Hushan; Lin, Jie; Ajani, Jaffer A; Wu, Xifeng
Genetic Variations in microRNA-related Genes Are Novel Susceptibility Loci for Esophageal Cancer Risk
MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors and modulate the expression of approximately one-third of all human genes. To test the hypothesis that adverse alleles in miRNA-related genes may increase the risk for esophageal cancer, we assessed the associations between esophageal cancer risk and 41 potentially functional single-nucleotide polymorphisms (SNPs) in 26 miRNA-related genes in a case-control study of 346 Caucasian esophageal-cancer patients (85.5% with esophageal adenocarcinoma) and 346 frequencymatched (age, gender, and ethnicity) controls. Seven SNPs were significantly associated with esophageal cancer risk. The most notable finding was that the SNP rs6505162, which is located in the pre-mir423 region, was associated with a per-allele odds ratio of 0.64 (95% confidence interval [CI], 0.51-0.80; P for trend < 0.0001). This association remained significant after we corrected for multiple comparisons. A common haplotype of the GEMIN4 gene was associated with a significantly reduced risk of esophageal cancer (odds ratio = 0.65; 95% CI, 0.42-0.99). We performed a combined unfavorable genotype analysis to further evaluate the cumulative effects of the promising (risk-associated) SNPs. In comparison with the low-risk group (fewer than three unfavorable genotypes), the medium-risk group (three unfavorable genotypes) had a 2.00-fold (95% CI=1.31-3.08) increased risk and the high-risk group (more than three unfavorable genotypes) had a 3.14-fold (95% CI=2.03-4.85) increased risk (P for trend < 0.0001). Results for the risk of esophageal adenocarcinoma were similar to the overall risk results. The present study provides the first evidence that miRNAs may affect esophageal cancer risk in general and that specific genetic variants in miRNA-related genes may affect esophageal cancer risk individually and jointly.
Ye, Yuanqing; Wang, Kenneth K.; Gu, Jian; Yang, Hushan; Lin, Jie; Ajani, Jaffer A.
From the radiologic pathology archives: esophageal neoplasms: radiologic-pathologic correlation.
Esophageal neoplasms have a wide spectrum of clinical features, pathologic findings, and imaging manifestations. Leiomyomas are the most common benign esophageal neoplasm, typically appearing as smoothly marginated intramural masses. Fibrovascular polyps arise in the cervical esophagus, gradually elongating as they are pulled inferiorly by esophageal peristalsis. Granular cell tumors are generally incidental small intramural masses with an appearance similar to that of leiomyomas. Malignant esophageal neoplasms are a common cause of cancer mortality, particularly squamous cell carcinoma (SCC) and adenocarcinoma. Both of these tumors occur in older men, most often appearing as irregular infiltrative lesions at barium examination, with evidence of tumor spread beyond the esophagus at cross-sectional imaging. Adenocarcinoma arises from Barrett esophagus and is much more likely than SCC to involve the gastroesophageal junction. Esophageal involvement by lymphoma is usually secondary to tumor spread from the stomach or mediastinum. Spindle cell carcinoma is a biphasic malignancy with carcinomatous and sarcomatous elements that forms a bulky polypoid intraluminal mass. Neuroendocrine carcinoma is an aggressive neoplasm that may be hypervascular and is usually associated with metastatic disease at presentation. Understanding the imaging appearances and pathologic bases of esophageal neoplasms is essential for their detection, differential diagnosis, staging, and treatment planning. PMID:23842973
Lewis, Rachel B; Mehrotra, Anupamjit K; Rodriguez, Pablo; Levine, Marc S
Metastasis of Esophageal Cancer.
National Technical Information Service (NTIS)
Metastatic involvement (59.2%) was noted in esophageal cancer during autopsy on 710 cases, with lymphogenic metastasis predominating over hematogenic metastasis. In those dying soon after radiation therapy there were metastasis in 49% and in 30% after sur...
A. I. Pirogov V. D. Ryndin
... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... chance of developing esophageal cancer increases with age. Squamous cell carcinoma of the esophagus is more common in blacks ...
Genetics of Eosinophilic Esophagitis.
National Technical Information Service (NTIS)
Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals...
M. Rothenberg
Genetics of Eosinophilic Esophagitis.
National Technical Information Service (NTIS)
Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals...
M. E. Rothenberg
Neoadjuvant chemoradiotherapy for esophageal/gastroesophageal carcinoma
Background Esophageal/gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Methods Consecutive patients with distal esophageal/GEJ adenocarcinoma (?T2 or N+) treated from July 2010 to October 2011 were identified. Treatment included neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy (ILE). PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Results Over this timeframe, 16 patients completed trimodality therapy. All were male, median age of 60 years (45-72 years). All tumors were grade 2-3 with mean tumor length of 4.4 cm (1-9 cm). A median of 6 cycles (5-9 cycles) neoadjuvant carboplatin/paclitaxel were administered. Average time from diagnosis to CRT completion was 76 days (44-141 days) and 60 days (35-92 days) from CRT end to surgery. Neoadjuvant CRT was well tolerated with mean weight loss of 3.9 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13 days (8-28 days). Pathologic complete response (pCR) was seen in 38% of patients, microscopic residual disease (isolated tumor cells or <2 mm) in 31%, and macroscopic residual disease remained in 31%. Mean SUV reduction was 41% (0-100%). Of 11 patients with ?35% SUV decrease, 45% had pCR and 27% had microscopic residual disease. Three patients had signet ring features. Of these, 2 had no SUV reduction and all had gross residual disease, including the only patient with positive nodal disease. Conclusions Trimodality therapy utilizing concurrent carboplatin/paclitaxel and radiotherapy to 50.4 Gy followed by surgery was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.
Nurkin, Steven J.; Fong, Mei Ka; Groman, Adrienne; Flaherty, Leayn; Malhotra, Usha; LeVea, Charles M.; Yendamuri, Sai; Warren, Graham W.; Nava, Hector R.; May, Kilian S.
Isolated cervical esophageal reconstruction for rare esophageal tumors
Background. Isolated defects in the cervical esophagus in patients who have not undergone total laryngec- tomy are uncommon. We report 2 cases of rare esophageal tumors requiring reconstruction of the cervical esophagus after tumor resection. Methods and Results. The patients were a 51-year-old woman with an esophageal granular cell tumor and a 54-year- old woman with an esophageal schwannoma. Both
Vincent P. Marin; Peirong Yu; Randal S. Weber
P66shc and its downstream Eps8 and Rac1 proteins are upregulated in esophageal cancers
Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to be related to cell proliferation and carcinogenesis. Whereas p46shc and p52shc drive the reaction forward, the role of p66shc in cancers remains to be understood clearly. Hence, their expression in cancers needs to be evaluated carefully so that Shc analysis may provide prognostic information in the development of carcinogenesis. In the present study, the expression of p66shc and its associate targets namely Eps8 (epidermal pathway substrate 8), Rac1 (ras-related C3 botulinum toxin substrate1) and Grb2 (growth factor receptor bound protein 2) were examined in fresh tissue specimens from patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma using western blot analysis. A thorough analysis of both esophageal squamous cell carcinoma and adenocarcinoma showed p66shc expression to be significantly higher in both types of carcinomas as compared to the controls. The controls of adenocarcinoma show a higher basal expression level of p66shc as compared to the controls of squamous cell carcinoma. The expression level of downstream targets of p66shc i.e., eps8 and rac1 was also found to be consistently higher in human esophageal carcinomas, and hence correlated positively with p66shc expression. However the expression of grb2 was found to be equal in both esophageal squamous cell carcinoma and adenocarcinoma. The above results suggest that the pathway operated by p66shc in cancers does not involve the participation of Ras and Grb2 as downstream targets instead it operates the pathway involving Eps8 and Rac1 proteins. From the results it is also suggestive that p66shc may have a role in the regulation of esophageal carcinomas and represents a possible mechanism of signaling for the development of squamous cell carcinoma and adenocarcinoma of esophagus.
Association of Esophageal Inflammation, Obesity and Gastroesophageal Reflux Disease: From FDG PET/CT Perspective
Objective Gastroesophageal reflux disease (GERD) is associated with bothersome symptoms and neoplastic progression into Barrett's esophagus and esophageal adenocarcinoma. We aim to determine the correlation between GERD, esophageal inflammation and obesity with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Methods We studied 458 subjects who underwent a comprehensive health check-up, which included an upper gastrointestinal endoscopy, FDG PET/CT and complete anthropometric measures. GERD symptoms were evaluated with Reflux Disease Questionnaire. Endoscopically erosive esophagitis was scored using the Los Angeles classification system. Inflammatory activity, represented by standardized uptake values (SUVmax) of FDG at pre-determined locations of esophagus, stomach and duodenum, were compared. Association between erosive esophagitis, FDG activity and anthropometric evaluation, including body mass index (BMI), waist circumference, visceral and subcutaneous adipose tissue volumes were analyzed. Results Subjects with erosive esophagitis (n?=?178, 38.9%) had significantly higher SUVmax at middle esophagus (2.69�0.74 vs. 2.41�0.57, P<.001) and esophagogastric junction (3.10�0.89 vs. 2.38�0.57, P<.001), marginally higher at upper esophageal sphincter (2.29�0.42 vs. 2.21�0.48, P?=?.062), but not in stomach or duodenum. The severity of erosive esophagitis correlated with SUVmax and subjects with Barrett's esophagus had the highest SUVmax at middle esophagus and esophagogastric junction. Heartburn positively correlated with higher SUVmax at middle oesophagus (r?=?.262, P?=?.003). Using multivariate regression analyses, age (P?=?.027), total cholesterol level (P?=?.003), alcohol drinking (P?=?.03), subcutaneous adipose tissue (P<.001), BMI (P<.001) and waist circumference (P<.001) were independently associated with higher SUVmax at respective esophageal locations. Conclusions Esophageal inflammation demonstrated by FDG PET/CT correlates with endoscopic findings and symptomatology of GERD. Obesity markers, both visceral and general, are independent determinants of esophageal inflammation.
Lee, Yi-Chia; Wang, Shan-Ying; Chiu, Han-Mo; Tu, Chia-Hung; Wang, Hsiu-Po; Lin, Jaw-Town; Wu, Ming-Shiang; Yang, Wei-Shiung
In Vivo Cancer Biomarkers of Esophageal Neoplasia
Summary The emergence of in vivo cancer biomarkers is promising tool for early detection, risk stratification, and therapeutic intervention in the esophagus, where adenocarcinoma is increasing at a rate that is faster than any other in industrialized nations. Exciting advances in target identification, probe development, and optical instrumentation are creating tremendous new opportunities for advancing techniques of molecular imaging. Progress in these areas is being made with small animal models of esophageal cancer using surgical approaches to induce reflux of acid and bile, and these findings are beginning to be evaluated in the clinic. Further identification of relevant targets, characterization of specific probes, and development of endoscopic imaging technologies are needed to further this direction in the field of molecular medicine. In the future, new methods that use in vivo cancer biomarkers for the early detection of neoplastic changes in the setting of Barrett's esophagus will become available.
Lu, Shaoying; Wang, Thomas D
Adenocarcinoma following urinary diversion
The use of bowel segments in urinary diversions has been associated with an increased risk of neoplasia. This report describes three cases of intestinal adenocarcinoma following urinary diversion. In the first case, a 73-year-old woman developed moderately-differentiated colonic adenocarcinoma in her Indiana pouch 10.5 years after cystectomy. The second case involved a 77-year-old man with well-differentiated adenocarcinoma in his Indiana pouch 9 years after radical cystoprostatectomy and en bloc urethrectomy. The third case involved a 38-year-old man with moderately-differentiated adenocarcinoma arising in his ileal conduit 33 years after the creation of the conduit. These cases highlight the diagnostic signs of adenocarcinoma arising in urinary diversions and emphasize the importance of lifelong surveillance in these patients.
Jian, Peter Yicum; Godoy, Guilherme; Coburn, Michael; Lynch, Garrett; Ro, Jae Y.; Zhai, Qihui "Jim"; Nishino, Michiya; Lerner, Seth P.
Clinical implications and pathogenesis of esophageal remodeling in eosinophilic esophagitis.
In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in the epithelium and subepithelium where lamina propria fibrosis, expansion of the muscularis propria, and increased vascularity occur. The clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Available therapies have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic end points account for the fundamental contributions of esophageal remodeling to overall disease activity. PMID:24813517
Hirano, Ikuo; Aceves, Seema S
Immunohistochemical analysis on potential new molecular targets for esophageal cancer.
Despite multimodal therapeutic options, esophageal cancer is still among the most deadly malignancies. In the past decade, targeted therapy has shown great potential in other cancers, but data on esophageal carcinoma are still rare. Five potential new molecular targets in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) were investigated for their expression characteristics: vascular endothelial growth factor receptor (VEGFR)-3, human epidermal growth factor receptor-2, stem cell growth factor receptor, tissue inhibitors of metalloproteinase (TIMP)-4 and TIMP-3. One hundred seventy-one EAC and ESCC tissue samples obtained from patients undergoing esophagectomy from 2000 to 2008 were included. Clinical data were evaluated retrospectively. Immunohistochemical staining was performed using tumor tissue with and without neoadjuvant treatment and healthy tissue. For samples without neoadjuvant treatment, expression of all targets was higher in tumor tissue than in healthy tissue except for VEGFR-3 (>98% expression in both tissues). For TIMP-4, TIMP-3 and stem cell growth factor receptor, trends to higher expression in tumor tissue were also found in EAC and ESCC that had received neoadjuvant treatment. Using Matched-pair analysis, we compared target expression in tumor tissue with and without neoadjuvant treatment. Only TIMP-3 had significantly lower expression in neoadjuvant treated tumor tissue (EAC: P = 0.059, ESCC: P = 0.006). TIMP-4, TIMP-3 and VEGFR-3 appear to qualify for targeted therapy in esophageal cancer because of their high expression in neoplastic tissue. TIMP-3 appears to be downregulated in neoadjuvantly treated esophageal cancer, and VEGFR-3 shows high expression in healthy mucosa leading to severe side effects by molecular targeting. Thus, TIMP-4 seems the most promising target. PMID:23551625
Maurer, J; Sch�pp, M; Thurau, K; Haier, J; K�hler, G; Hummel, R
Adenocarcinoma complicating Barrett's esophagus: an analysis of cell proliferation.
In Japan, cases of Barrett's esophagus with concurrent adenocarcinoma are relatively rare. We report herein a case of long-segment Barrett's esophagus-associated adenocarcinoma in a 72-year-old Japanese man. The surgical specimen showed that an ulcerating tumor, measuring 5.5 x 3.9 cm, was present in the lower esophagus adjacent to the esophagogastric junction, the background lower esophagus having an erythematous appearance. Histologically, the ulcerating tumor was a well-to-moderately differentiated tubular adenocarcinoma, with a small area of signet ring cell carcinoma invading the adventitia. In addition, the esophageal epithelium was replaced by columnar epithelium (9.5 cm in length) with multifocal dysplastic changes. Immunohistochemically, the number of Ki-67-positive cells gradually increased, moving from the normal gastric mucosa (mean Ki-67 labeling index [mKLI], 2.6%) through Barrett's epithelium (mKLI, 12.9%), low-grade dysplasia (mKLI, 16.9%), and high-grade dysplasia (mKLI. 23.7%) to invasive carcinoma, in that order, with labeling higher in the invasive tubular adenocarcinoma elements (mKLI, 40.5%) than in areas of signet ring cell carcinoma (mKLI, 20.4%). Findings in our patient suggest that increased cellular proliferation plays an integral part, in the progression of Barrett's metaplasia to adenocarcinoma. The collection of further cases for analysis will be necessary to confirm this hypothesis. PMID:11428588
Matsumoto, Y; Arai, N; Mieno, H; Murakami, K; Ishii, K; Mitomi, H
Esophageal Metastasis to the Iris Effectively Palliated Using Stereotactic Body Radiation Therapy and Adjuvant Intravitreal Chemotherapy: Case Report and Literature Review
We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris.
Dhakal, Sughosh; Lema, Gareth M.C.; DiLoreto, David A.; Katz, Alan W.
Esophageal Perforation in Adults
Objective: To evaluate the outcome of aggressive conservative therapy in patients with esophageal perforation. Summary Background Data: The treatment of esophageal perforation remains controversial with a bias toward early primary repair, resection, and/or proximal diversion. This review evaluates an alternate approach with a bias toward aggressive drainage of fluid collections and frequent CT and gastographin UGI examinations to evaluate progress. Methods: From 1992 to 2004, 47 patients with esophageal perforation (10 proximal, 37 thoracic) were treated (18 patients early [<24 hours], 29 late). There were 31 male and 16 females (ages 18�90 years). The etiology was iatrogenic (25), spontaneous (14), trauma (3), dissecting thoracic aneurysm (3), and 1 each following a Stretta procedure and Blakemore tube placement. Results: Six of 10 cervical perforations underwent surgery (3 primary repair, 3 abscess drainage). Nine of 10 perforations healed at discharge. In 37 thoracic perforations, 2 underwent primary repair (1 iatrogenic, 1 spontaneous) and 4 underwent limited thoracotomy. Thirty-4 patients (4 cervical, 28 thoracic) underwent nonoperative treatment. Thirteen of the 14 patients with spontaneous perforation (thoracic) underwent initial nonoperative care. Overall mortality was 4.2% (2 of 47 patients). These deaths represent 2 of 37 thoracic perforations (5.4%). There were no deaths in the 34 patients treated nonoperatively. Esophageal healing occurred in 43 of 45 surviving patients (96%). Subsequent operations included colon interposition in 2, esophagectomy for malignancy in 3, and esophagectomy for benign stricture in 2. Conclusions: Aggressive treatment of sepsis and control of esophageal leaks leak lowers mortality and morbidity, allow esophageal healing, and avoid major surgery in most patients.
Vogel, Stephen B.; Rout, W Robert; Martin, Tomas D.; Abbitt, Patricia L.
Two Cases of Esophageal Eosinophilia: Eosinophilic Esophagitis or Gastro-Esophageal Reflux Disease?
Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease are among the major causes of isolated esophageal eosinophilia. Isolated esophageal eosinophilia meeting criteria for EoE may respond to proton pump inhibitor (PPI) treatment. This entity is termed proton pumps inhibitor responsive esophageal eosinophilia (PPI-REE). Gastro-esophageal reflux is thought to comprise a subgroup of patients with PPI-REE. According to the latest guidelines, PPI responsiveness distinguishes people with PPI-REE from patients having EoE (non-responders). In this report, two unusual cases with findings belonging to both EoE and PPI-REE are discussed with known and unknown facts.
Yilmaz, Ozlem; Karagol, Hacer Ilbilge Ertoy; Topal, Erdem; Unlusoy, Aysel Aksu; Egritas, Odul; Gonul, Ipek Isik; Bakirtas, Arzu
Early Experience of Thoracoscopic Aortopexy for Severe Tracheomalacia in Infants After Esophageal Atresia and Tracheo-esophageal Fistula Repair.
Abstract Background: Aortopexy is the most effective treatment for severe tracheomalacia associated with esophageal atresia with distal tracheo-esophageal fistula (EA/TOF). In the last few years, the thoracoscopic approach has been proposed, but the number of patients treated is limited. The purpose of this study is to review our initial experience with thoracoscopic aortopexy. Patients and Methods: A retrospective review of medical records was performed on EA/TOF patients undergoing thoracoscopic aortopexy at the Great Ormond Street Hospital for Sick Children (London, United Kingdom) from January 2009 to May 2012. Patient demographics, indication, perioperative course, and long-term results when available were noted. Results: Four patients underwent a successful thoracoscopic aortopexy, with no operation being converted. No morbidity or mortality was associated with the procedure. Length of postoperative stay ranged from 2 to 4 days. All patients were relieved of their symptoms, and no recurrence was noted. Conclusions: Thoracoscopic aortopexy is a feasible and successful treatment for severe tracheomalacia in EA/TOF patients. The complication rate may be lower than after the open procedure and is more satisfactory in terms of cosmetic appearance. However, we need a larger and prospective study with a longer follow-up to confirm these preliminary results. PMID:24987844
Arnaud, Alexis P; Rex, Dean; Elliott, Martin J; Curry, Joe; Kiely, Edward; Pierro, Agostino; Cross, Kate; Coppi, Paolo De
Concurrent superficial squamous cell carcinoma of the esophagus and early gastric adenocarcinoma. Report of a case.
We report a patient with concurrent superficial carcinomas of the esophagus and stomach. The tumors occurred in a 68-year-old woman. The esophageal tumor was an intramucosal squamous cell carcinoma, and the gastric tumor an intramucosal adenocarcinoma, type III in the Japanese classification of early gastric cancer. This is the first reported case of associated superficial esophageal and gastric cancers originating from a Western country. Such an association may be more frequent than realized, and therefore it is important to examine both the stomach and esophagus if a patient has one of these tumors. PMID:1556406
Flejou, J F; Jones, E A; Diomande, I M; Gayet, B; Henin, D; Potet, F
Management of gastric adenocarcinoma
Gastric adenocarcinoma is the second most common cause of cancer death worldwide. The prognosis for patients with gastric\\u000a adenocarcinoma depends on the stage of the disease at the time of diagnosis and treatment. Early gastric cancer, limited to\\u000a the mucosa and submucosa, is best treated surgically and has a five-year survival rate of 70�95%. Surgical resection remains\\u000a the primary curative
P. Khosravi Shahi; V. M. D�az Mu�oz de la Espada; P. Garc�a Alfonso; S. Encina Garc�a; Y. Izarzugaza Per�n; J. L. Arranz Cozar; B. Hern�ndez Mar�n; G. P�rez Manga
... determine if you have a ring or a web, your doctor may order one of these tests: Barium swallow test. This allows the radiologist to ... contribute to the development of esophageal rings and webs, your doctor probably will order a blood test for iron levels and, if you are deficient, ...
Gastric adenocarcinoma inducing portal hypertension: A rare presentation
Advanced gastric cancer usually presents with symptoms due to direct extension into adjacent viscera, distant metastases from lymphatic or hematogenic dissemination and peritoneal seeding. However, portal hypertension as a presentation of metastatic gastric cancer is rare and usually seen in association with other malignancies, e.g. hepatocellular and pancreatic carcinoma. We report a case of signet ring adenocarcinoma of the stomach that presented with esophageal and duodenal varices and bleeding due to portal hypertensive gastropathy. Pagetoid spread of cancer cells likely caused early metastasis and the unusual presentation. We also discussed the pathophysiology of development of portal hypertension in association with malignancies.
Ghosh, Pradipta; Miyai, Katsumi; Chojkier, Mario
Delayed diagnosis of high proximal tracheoesophageal fistula in esophageal atresia and a novel approach to the treatment of tracheomalacia by submanubrial tracheopexy.
An infant with esophageal atresia (EA) had delayed diagnosis of proximal tracheoesophageal fistula (TEF) and severe tracheomalacia. We recommend bronchoscopy via laryngeal mask or rigid bronchoscopy to rule out associated TEF in infants diagnosed with esophageal atresia, as flexible bronchoscopy via endotracheal tube may not provide complete visualization of the trachea. We also describe a novel cervical approach to tracheopexy via neck incision for treatment of associated severe tracheomalacia in this infant. PMID:24634808
Bjornson, Candice; Brindle, Mary; Bailey, Ja Michelle; Mitchell, Ian; Soles, Melissa
Tracheo-esophageal fistula: Successful palliation after failed esophageal stent
The incidence of tracheo-esophageal (TO) fistula is on the rise, especially after palliative management for esophageal malignancies. We report a case of cancer of esophagus who after chemotherapy and radiotherapy developed TO fistula. Placement of an esophageal stent helped him in taking food orally, but his cough and dyspnoea continued to worsen. Fibreoptic bronchoscopy demonstrated a severely compressed trachea secondary to protrusion of esophageal stent which responded very well to an Ultraflex-covered tracheal stent and the patient achieved relief from cough and dyspnoea.
Chawla, Rakesh K.; Madan, Arun; Chawla, Kiran
Tracheo-esophageal fistula: Successful palliation after failed esophageal stent.
The incidence of tracheo-esophageal (TO) fistula is on the rise, especially after palliative management for esophageal malignancies. We report a case of cancer of esophagus who after chemotherapy and radiotherapy developed TO fistula. Placement of an esophageal stent helped him in taking food orally, but his cough and dyspnoea continued to worsen. Fibreoptic bronchoscopy demonstrated a severely compressed trachea secondary to protrusion of esophageal stent which responded very well to an Ultraflex-covered tracheal stent and the patient achieved relief from cough and dyspnoea. PMID:22919174
Chawla, Rakesh K; Madan, Arun; Chawla, Kiran
Esophageal Rupture as a Primary Manifestation in Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is a chronic inflammatory process characterized by symptoms of esophageal dysfunction and, histologically, by eosinophilic infiltration of the esophagus. In adults, it commonly presents with dysphagia, food impaction, and chest or abdominal pain. Chronic inflammation can lead to diffuse narrowing of the esophageal lumen which may cause food impaction. Endoscopic procedures to relieve food impaction may lead to complications such as esophageal perforation due to the friability of the esophageal mucosa. Spontaneous transmural esophageal rupture, also known as Boerhaave's syndrome, as a primary manifestation of EoE is rare. In this paper, we present two adult patients who presented with esophageal perforation as the initial manifestation of EoE. This rare complication of EoE has been documented in 13 other reports (11 adults, 2 children) and only 1 of the patients had been previously diagnosed with EoE. A history of dysphagia was present in 1 of our patients and in the majority of previously documented patients. Esophageal perforation is a potentially severe complication of EoE. Patients with a history of dysphagia and patients with spontaneous esophageal perforation should warrant an evaluation for EoE.
Vernon, Natalia; Mohananey, Divyanshu; Ghetmiri, Ehsan; Ghaffari, Gisoo
Esophageal cancer proliferation is mediated by cytochrome P450 2C9 (CYP2C9).
Cytochrome P450 epoxygenases (CYP450) have been recently shown to promote malignant progression. Here we investigated the mRNA and protein expression and potential clinical relevance of CYP2C9 in esophageal cancer. Highest expression was detected in esophageal adenocarcinoma (EAC; n=78) and adjacent esophageal mucosa (NEM; n=79). Levels of CYP2C9 in EAC and NEM were significantly higher compared to esophageal squamous cell carcinoma (ESCC; n=105). Early tumor stages and well-differentiated tumors showed a significantly higher CYP2C9 expression compared to progressed tumors. Moreover, CYP2C9 expression was correlated to high Ki-67 labeling indices in EAC and Ki-67 positive tumor cells in EAC and ESCC. Selective inhibition of CYP2C9 decreased tumor cell proliferation (KYSE30, PT1590 and OE19) in vitro, which was abolished by 11,12-epoxyeicosatrienoic acid (11,12-EET). Cell-cycle analysis using FACS revealed that inhibition of CYP2C9 leads to a G0/G1 phase cell-cycle arrest. CYP2C9 seems to be relevant for early esophageal cancer development by promoting tumor cell proliferation. Pharmacological inhibition of CYP2C9 might contribute to a more efficient therapy in CYP2C9 highly expressing esophageal cancers. PMID:21167292
Schmelzle, Moritz; Dizdar, Levent; Matthaei, Hanno; Baldus, Stephan E; Wolters, Judith; Lindenlauf, Nina; Bruns, Ingmar; Cadeddu, Ron-Patrick; Kr�pil, Feride; Topp, Stefan A; Schulte am Esch, Jan; Eisenberger, Claus F; Knoefel, Wolfram T; Stoecklein, Nikolas H
Nonmuscle myosin IIA is associated with poor prognosis of esophageal squamous cancer.
Nonmuscle myosin IIA (myosin IIA) is a force-producing protein involved in the process of cell migration. Its expression has been considered as a bad prognostic indicator in stage I lung adenocarcinoma. However, the expression and clinical significance of myosin IIA in esophageal cancer has not been explored. In this study, we investigate the expression level of myosin IIA in 50 esophageal squamous cancer and 30 adjacent normal esophageal tissues by immunohistochemical staining and correlated its expression with clinicopathological features. Myosin IIA was expressed in all esophageal squamous cancer tissues (100%) and 8 of 30 adjacent normal tissues (26.7%, P = 0.000). In cancer tissues, elevated myosin IIA expression level was significantly correlated with increasing metastatic lymph nodes, poorer cancer differentiation, and advanced tumor stage. Further univariate analysis suggested that strong myosin IIA expression was associated with a significantly shorter overall survival (P = 0.021). In addition, MYH9 SiRNA was transfected into esophageal squamous cancer cell line (KYSE-510) to study the role of myosin IIA in cell migration. SiRNA-mediated depletion of myosin IIA in KYSE-510 cells significantly increased cell-matrix adhesion and attenuated cell migration ability (P = 0.000). In conclusion, these findings indicate that overexpression of myosin IIA may contribute to the progression and poor prognosis of esophageal squamous cancer, and this effect may be associated with increased cancer cell migration. PMID:21951916
Xia, Z-K; Yuan, Y-C; Yin, N; Yin, B-L; Tan, Z-P; Hu, Y-R
Eosinophilic esophagitis: Pathobiology and management
Patients with eosinophilic esophagitis present with symptoms similar to those found in GERD, along with dense esophageal eosinophilia\\u000a that persist despite aggressive acid blockade. A dramatic increase in prevalence of eosinophilic esophagitis over the past\\u000a several years has provided clinicians with a new explanation for previously unexplained dysphagia, food impaction, and vomiting.\\u000a In light of this recognition, an increasing number
Jessica J. Lee; Glenn T. Furuta
Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer
Background: Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in the world. In a nested case-cohort study that originated from two cancer prevention trials in Linxian, we examined the relationship between these cancers and two polymorphisms in the DNA repair gene XRCC1.Methods: We conducted a case-cohort
Luke D. Ratnasinghe; Christian Abnet; You-Lin Qiao; Rama Modali; Rachael Stolzenberg-Solomon; Zhi-Wei Dong; Sanford M. Dawsey; Steven D. Mark; Philip R. Taylor
Long-term respiratory complications of congenital esophageal atresia with or without tracheoesophageal fistula: an update.
Despite early surgical repair, congenital esophageal atresia with or without tracheoesophageal fistula (EA � TEF) has long-term effects on respiratory and gastrointestinal function. This review updates summarizes research published since 2003 on long-term respiratory complications in patients with a history of EA � TEF. Pulmonary hypoplasia appears to not be rare in patients with EA � TEF. Tracheomalacia is common and is associated with respiratory symptoms in childhood. Aspiration, associated with esophageal dysmotility and/or gastroesophageal reflux, may lead to reduced pulmonary function and bronchiectasis. Pulmonary function is generally normal, although lower than in control patients, and restrictive defects tend to be commoner than obstructive defects. Abnormal airway reactivity is common and, along with respiratory symptoms, is associated with atopy. However, the inflammatory profile in EA � TEF patients based on bronchial biopsies and exhaled nitric oxide differs from typical allergic asthma. Recent studies suggest that in older patients, respiratory symptoms tend to be associated with atopy, but abnormal lung function tends to be associated with gastroesophageal reflux and with chest wall abnormalities. Early detection and management of aspiration may be important to help prevent decrements in pulmonary function and serious long-term complications in EA � TEF patients. PMID:23679034
Kovesi, T
[Achalasia and esophageal cancer].
During the period included between January 1970 and December 1990, we studied 242 patients with manometric and radiological diagnosis of esophageal achalasia. Eight of these patients (3.3%) developed during the evolution of their disease an esophageal carcinoma. Eight cases showed histologic type of epidermoid carcinoma: 3 differentiated, 3 semi-differentiated and 2 anaplastic. Therapy for achalasia was: one patient, Heller myotomy, 4 patients, dilatations with bougies in numerous opportunities, and the other two patients receive no treatment for achalasia. Two patients reported tracheobronchial fistulas as complication of carcinoma. Treatment received for carcinoma included: three patients, radiotherapy (4000 rads); one patient, chemotherapy; one patient, chemotherapy and radiotherapy, one resection surgery and two patients feeding gastrostomy. All of the eight patients died within the year of diagnosis of epidermoid carcinoma. PMID:1300847
Corti, R E; Monastra, L; Fern�ndez Marty, P; Barco, J C; Ferro, F E; Galindo, F; Musi, A O; Kogan, Z
[Giant esophageal fibrovascular polyp].
Fibrovascular polyps are extremely rare benign neoplasias of the esophagus, which usually originate in the lower cricoid area. They do not produce any discomfort in the patient for a long time, however it may make itself evident by the patient's regurgitation of the polyp, producing asphyxia or, more frequently, dysphagia. The case of a 58 year old male patient is presented herein, with a 9 month record of dysphagia, weight loss and intermittent melena. The barium x-ray showed a distended esophagus, with a tumor running from the upper esophageal sphincter to the cardia. The endoscopy confirmed the presence of a pediculated tumor, implanted in the cervical esophagus. Surgeons suspected the potential malignancy of the tumor and performed a transhiatal esophagectomy. The final pathologic diagnosis was giant fibrovascular esophageal polyp. PMID:14532922
Palacios, Fernando; Contardo, Carlos; Guevara, Jorge; Vera, Augusto; Aguilar, Luis; Huam�n, Manuel; Palomino, Am�rico; Yabar, Alejandro
Prognostic significance of differentially expressed miRNAs in esophageal cancer
Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21, and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126, and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-?2 expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell de-differentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e, and miR-200a expression were associated with shorter overall and disease-free survival in esophageal adenocarcinoma patients; however, miR-16-2, miR-30e, and miR-200a expression was not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study.
Hu, Yuxin; Correa, Arlene M.; Hoque, Ashraful; Guan, Baoxiang; Ye, Fei; Huang, Jie; Swisher, Stephen G.; Wu, Tsung Teh; Ajani, Jaffer A.; Xu, Xiao-chun
Esophageal and Gastric Injuries
\\u000a Traumatic lesions of the esophagus can be classified into. Primary lesions, Perforations, Ruptures, Secondary lesions, Fistulas,\\u000a Strictures Perforations: Perforations are due to internal or external forces. The vast majority of esophageal perforations\\u000a occur iatrogenic (e.g., endoscopy, dilatation, transesophageal echocardiography (TEE), Sengstaken�Blakemore tubes, endotracheal\\u000a tubes). Penetrating injuries due to external forces (e.g., stab wounds, gunshots) are less frequent. For the therapeutic
Paul M. Schneider; Georg Lurje; Peter Bauerfeind; Marc Schiesser
ABL regulation by AXL promotes cisplatin resistance in esophageal cancer.
Esophageal adenocarcinoma (EAC) is characterized by resistance to chemotherapy and poor outcome. Although cisplatin (CDDP) has been used as a first-line therapy in patients with EAC, resistance remains a major clinical problem. The AXL receptor tyrosine kinase, originally isolated as a transforming gene from leukemia, is overexpressed in several solid tumors. Herein, we assessed AXL protein expression in human EACs and examined its role in CDDP resistance in human EAC cells. AXL overexpression was detected in more than 50% of tumors examined. Elevating AXL in nonoverexpressing cells doubled the CDDP IC(50) and increased cell survival three-fold, while attenuating AXL in overexpressing cells reduced survival two-fold. The effects of AXL modulation on cell survival were associated with changes in cellular and molecular markers of apoptosis. Mechanistic investigations revealed that AXL blocked CDDP-induced activation of endogenous p73? (TP73), reducing its protein half-life, and inhibited CDDP-induced levels of p-c-ABL(Y412) and p-p73?(Y99). These changes were associated with a disruption of c-ABL/p73? protein interactions due to association with c-ABL in the cytoplasm, thereby blocking nuclear accumulation of c-ABL and phosphorylation of p73? in response to DNA damage. Together, our results establish that AXL promotes CDDP resistance in esophageal adenocarcinoma and argue that therapeutic targeting of AXL may sensitize these cancers to DNA-damaging drugs. PMID:23117882
Hong, Jun; Peng, Dunfa; Chen, Zheng; Sehdev, Vikas; Belkhiri, Abbes
O-6-methylguanine-deoxyribonucleic acid methyltransferase methylation enhances response to temozolomide treatment in esophageal cancer
Background: World-wide, esophageal cancer is a growing epidemic and patients frequently present with advanced disease that is surgically inoperable. Hence, chemotherapy is the predominate treatment. Cytotoxic platinum compounds are mostly used, but their efficacy is only moderate. Newer alkylating agents have shown promise in other tumor types, but little is known about their utility in esophageal cancer. Methods: We utilized archived human esophageal cancer samples and esophageal cancer cell lines to evaluate O-6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) hypermethylation status and determined sensitivity to the alkylating drug temozolomide (TMZ). Immunoblot analysis was performed to determine MGMT protein expression in cell lines. To assess and confirm the effect of TMZ treatment in a methylated esophageal cancer cell line in vivo, a mouse flank xenograft tumor model was utilized. Results: Nearly 71% (12/17) of adenocarcinoma and 38% (3/8) of squamous cell carcinoma (SCC) patient samples were MGMT hypermethylated. Out of four adenocarcinoma and nine SCC cell lines tested, one of each histology was hypermethylated. Immunoblot analyses confirmed that hypermethylated cell lines did not express the MGMT protein. In vitro cell viability assays showed the methylated Kyse-140 and FLO cells to be sensitive to TMZ at an IC50 of 52-420 ?M, whereas unmethylated cells Kyse-410 and SKGT-4 did not respond. In an in vivo xenograft tumor model with Kyse-140 cells, which are MGMT hypermethylated, TMZ treatment abrogated tumor growth by more than 60%. Conclusion: MGMT methylation may be an important biomarker in subsets of esophageal cancers and targeting by TMZ may be utilized to successfully treat these patients.
Hasina, Rifat; Surati, Mosmi; Kawada, Ichiro; Arif, Qudsia; Carey, George B.; Kanteti, Rajani; Husain, Aliya N.; Ferguson, Mark K.; Vokes, Everett E.; Villaflor, Victoria M.; Salgia, Ravi
Clinical applications of esophageal manometry
In recent times, there has been considerable controversy over the accuracy, reproducibility, and importance of pressures measured in the esophagus and its sphincters. This has led to confusion about the potential clinical utility of esophageal manometry in the diagnosis of abnormalities of esophageal function. There are at least two important aspects that should be considered when formulating an opinion concerning
D. O. Castell
Pill-induced esophageal injury
We report four cases of esophageal injury associated with the ingestion of commonly prescribed tablets or capsules. History and clinical characteristics of these cases suggest that the medications failed to transit the esophagus and acted locally to produce esophagitis. A search of English- and foreign-language medical journals documented 221 similar cases due to 26 different types of medication. While most
James Walter Kikendall; Arnold C. Friedman; Morakinyo Anthony Oyewole; David Fleischer; Lawrence F. Johnson
Eosinophilic Esophagitis: Biology to Therapy
Eosinophilic esophagitis, a recently recognized and growing clinical disorder over the past decade, is characterized by antigen-driven eosinophil accumulation in the esophagus. Symptoms frequently mimic those of gastroesophageal reflux disease (GERD) but the two diseases are quite distinct in terms of their histopathology, genetic signature, response to therapy, hereditary risk and association with allergy. Disease pathogenesis involves the interplay of external and genetic factors, particularly food antigens and the eosinophil chemoattractant eotaxin-3, respectively. Transcript signatures and animal models have uncovered the importance of adaptive T cell immunity involving IL-5 and IL-13 elicited esophageal epithelial cell responses. Notably, symptoms, dysregulated esophageal gene expression and pathology are largely reversible following reduction of specific food antigen exposure, as well as anti-inflammatory therapy, but chronic treatment is necessary to prevent relapse. As such, eosinophilic esophagitis is a disease with the unique features of chronic esophagitis, atopy, immune sensitization to oral antigens, reversibility and familial association.
Rothenberg, Marc E.
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.
Cigarette Smoking and Adenocarcinomas of the Esophagus and Esophagogastric Junction: A Pooled Analysis From the International BEACON Consortium
Background Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose�response, and duration of cigarette smoking cessation. Methods We used primary data from 10 population-based case�control studies and two cohort studies from the Barrett�s Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided. Results The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose�response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and ?10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar. Conclusions Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.
Kamangar, Farin; Whiteman, David C.; Freedman, Neal D.; Gammon, Marilie D.; Bernstein, Leslie; Brown, Linda M.; Risch, Harvey A.; Ye, Weimin; Sharp, Linda; Pandeya, Nirmala; Webb, Penelope M.; Wu, Anna H.; Ward, Mary H.; Giffen, Carol; Casson, Alan G.; Abnet, Christian C.; Murray, Liam J.; Corley, Douglas A.; Nyren, Olof; Vaughan, Thomas L.; Chow, Wong-Ho
Code of Federal Regulations, 2011 CFR
...false EAS Decoder. 11.33 Section 11.33 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements � 11.33 EAS Decoder. (a) An EAS Decoder must at a minimum be...
Code of Federal Regulations, 2011 CFR
...false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements � 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable...
Code of Federal Regulations, 2012 CFR
...COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements...CAP)-formatted EAS messages into EAS alert messages that comply with the EAS...Display and logging. For received alert messages formatted in both the...
Code of Federal Regulations, 2010 CFR
...false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements � 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable...
47 CFR 11.18 - EAS Designations.
Code of Federal Regulations, 2011 CFR
...EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General � 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential...
Code of Federal Regulations, 2010 CFR
...false EAS Decoder. 11.33 Section 11.33 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements � 11.33 EAS Decoder. (a) An EAS Decoder must at a minimum be...
47 CFR 11.18 - EAS Designations.
Code of Federal Regulations, 2010 CFR
...EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General � 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential...
Code of Federal Regulations, 2012 CFR
...false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements � 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable...
47 CFR 11.18 - EAS Designations.
Code of Federal Regulations, 2012 CFR
...EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General � 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential...
Code of Federal Regulations, 2013 CFR
...COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements...CAP)-formatted EAS messages into EAS alert messages that comply with the EAS...Display and logging. For received alert messages formatted in both the...
Code of Federal Regulations, 2013 CFR
...false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable...
47 CFR 11.18 - EAS Designations.
Code of Federal Regulations, 2013 CFR
...EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General § 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential...
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
Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities.
Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstays of current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy. PMID:24834141
Napier, Kyle J; Scheerer, Mary; Misra, Subhasis
Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis
Animal models are important for the development of novel therapies for esophageal cancer. Histone deacetylase 1 (HDAC1)/metastasis-associated gene (MTA1) complexes inhibit p53 acetylation and thus, inhibit p53-induced apoptosis. The aim of the present study was to evaluate HDAC1 and MTA1 expression in esophageal carcinogenesis in rats. The rats underwent a total gastrectomy followed by esophagojejunostomy to induce chronic duodenal content reflux esophagitis. The rats were sacrificed sequentially at 20, 30, 40 and 50 weeks post-surgery and the esophagi were examined. Immunohistochemical analysis was conducted to assess the expression and localization of HDAC1 and MTA1. At 20 weeks post-surgery, squamous proliferative hyperplasia and Barrett�s metaplasia (BM) were observed. While, adenocarcinoma-associated BM and squamous cell carcinoma were observed at 30�50 weeks post-surgery. The nuclear expression of HDAC1 and MTA1 was observed in all of the stages of squamous carcinogenesis and adenocarcinogenesis, although not in the normal esophageal epithelium. The expression of HDAC1 and MTA1 may be involved in duodenoesophageal reflux-induced neoplastic transformation of the esophageal mucosa into cancer cells with squamous and adeno differentiation.
Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities
Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstays of current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.
Napier, Kyle J; Scheerer, Mary; Misra, Subhasis
The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract
Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection.
Serum concentration and expression of Reg IV in patients with esophageal cancer: Age-related elevation of serum Reg IV concentration
Regenerating islet-derived family, member 4 (REG4, which encodes Reg IV) is a marker for cancer and inflammatory bowel disease. This study aimed to investigate the diagnostic utility of Reg IV measurement in sera from esophageal cancer patients. Reg IV expression was examined in 269 esophageal cancer samples by immunostaining and the Reg IV levels in sera were measured from 65 patients with esophageal squamous cell carcinoma (SCC) by enzyme-linked immunosorbent assay. No Reg IV staining was detected in 255 SCC and 4 small cell carcinoma samples, whereas Reg IV was stained in 4 of 10 (40%) adenocarcinoma samples. Serum Reg IV concentration in esophageal SCC patients was significantly higher compared to that of the control subjects (P=0.0003). A significant correlation between serum Reg IV concentration and age was found in control subjects (P<0.0001). When serum Reg IV concentration was analyzed according to age, the distribution of serum Reg IV concentration in patients with esophageal SCC was similar to that of the control subjects. These results suggest that Reg IV expression is highly specific for adenocarcinoma of the esophagus. Further investigation is required to clarify whether Reg IV serves as a serum tumor marker for esophageal cancer.
Acid corrosive esophagitis: radiographic findings.
Thirty-nine esophagograms of 24 patients after ingestion of muriatic acid (27% HCI) in suicide attempts were reviewed. All esophagograms were obtained in the acute, subacute, and chronic phases. In the acute and subacute phases, the radiographic findings consisted of mucosal edema, submucosal edema or hemorrhage, ulcerations, sloughing of the mucosa, atony, and dilatation. Strictures of the esophagus were present in the chronic phase. These radiographic findings were not different from those found in alkaline corrosive esophagitis. The severity of the corrosive esophagitis is considered related to the concentration, amount, viscosity, and duration of contact between the caustic agent and the esophageal mucosa. PMID:6770621
Muhletaler, C A; Gerlock, A J; de Soto, L; Halter, S A
Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis
Background Esophageal cancer ranks eighth among frequent cancers worldwide. Our aim was to investigate whether and at which neoplastic stage promoter hypermethylation of CAV1 is involved in human esophageal carcinogenesis. Methods Using real-time quantitative methylation-specific PCR (qMSP), we examined CAV1 promoter hypermethylation in 260 human esophageal tissue specimens. Real-time RT-PCR and qMSP were also performed on OE33 esophageal cancer cells before and after treatment with the demethylating agent, 5-aza-2�-deoxycytidine (5-Aza-dC). Results CAV1 hypermethylation showed highly discriminative ROC curve profiles, clearly distinguishing esophageal adenocarcinomas (EAC) and esophageal squamous cell carcinomas (ESCC) from normal esophagus (NE) (EAC vs. NE, AUROC?=?0.839 and p?0.0001; ESCC vs. NE, AUROC?=?0.920 and p?0.0001). Both CAV1 methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett�s metaplasia (BE), low-grade and high-grade dysplasia occurring in BE (D), EAC, and ESCC than in NE (all p?0.01, respectively). Meanwhile, among 41 cases with matched NE and EAC or ESCC, CAV1 NMVs in EAC and ESCC (mean?=?0.273) were significantly higher than in corresponding NE (mean?=?0.146; p?0.01, Student�s paired t-test). Treatment of OE33 EAC cells with 5-Aza-dC reduced CAV1 methylation and increased CAV1 mRNA expression. Conclusions CAV1 promoter hypermethylation is a frequent event in human esophageal carcinomas and is associated with early neoplastic progression in Barrett�s esophagus.
Endometrial Adenocarcinoma in Pregnancy
Objective. The coexistence of endometrial adenocarcinoma and pregnancy is rare. Most cases are discovered in the first trimester due to irregular bleeding or spontaneous abortion.Case. A 44-year-old woman, gravida 3, para 2, was admitted due to abnormal vaginal bleeding. After complete history, physical examination, and laboratory evaluation, she was diagnosed with spontaneous abortion and underwent a suction curettage. Pathological examination
A. Ayhan; S. Gunalp; C. Karaer; A. Gokoz; U. Oz
Opinion statement��Cervical adenocarcinomas are increasing in incidence each year, comprising up to 25% of all cervical cancers diagnosed in\\u000a the United States. This increase largely reflects the inherent difficulty in detecting glandular precursor lesions using current\\u000a screening practices. However, there also appears to be a recent shift in the epidemiology of the disease process with younger\\u000a women being diagnosed more
John O. Schorge; Lynne M. Knowles; Jayanthi S. Lea
[The role of esophageal sphincter tonus and of gastric motility in the extent of reflux esophagitis].
Thirty-two patients with symptomatic gastroesophageal reflux disease were investigated by esophagogastroduodenoscopy, 24 h pH monitoring, esophageal manometry and measurement of gastric emptying of solids, in order to elucidate the relative importance of lower esophageal sphincter tone, amount of acid reflux and gastric emptying on the degree of esophagitis. The mechanical competency of lower esophageal sphincter was significantly deranged in patients with moderate/severe esophagitis than in patients with mild esophagitis. The gastric emptying time was significantly delayed in patients with moderate/severe esophagitis than in patients with mild esophagitis. No relationship was observed between amount of acid reflux, lower esophageal sphincter function and gastric emptying time. Our results suggest that resting pressure of lower esophageal sphincter and the gastric motor function play a major role in severity of reflux esophagitis. PMID:1553047
Cogliandolo, A; Gulino, F M; Pustorino, S; Migliorato, D; Bottari, M; Saitta, F P; Micali, B
The Multifactorial Origin of Respiratory Morbidity in Patients Surviving Neonatal Repair of Esophageal Atresia
Esophageal atresia with or without tracheoesophageal fistula (EA?�?TEF) occurs in 1 out of every 3000 births. Current survival approaches 95%, and research is therefore focused on morbidity and health-related quality of life issues. Up to 50% of neonates with EA?�?TEF have one or more additional malformations including those of the respiratory tract that occur in a relatively high proportion of them and particularly of those with vertebral, anal, cardiac, tracheoesophageal, renal, and limb association. Additionally, a significant proportion of survivors suffer abnormal pulmonary function and chronic respiratory tract disease. The present review summarizes the current knowledge about the nature of these symptoms in patients treated for EA?�?TEF, and explores the hypothesis that disturbed development and maturation of the respiratory tract could contribute to their pathogenesis.
Fragoso, Ana Catarina; Tovar, Juan A.
The multifactorial origin of respiratory morbidity in patients surviving neonatal repair of esophageal atresia.
Esophageal atresia with or without tracheoesophageal fistula (EA?�?TEF) occurs in 1 out of every 3000 births. Current survival approaches 95%, and research is therefore focused on morbidity and health-related quality of life issues. Up to 50% of neonates with EA?�?TEF have one or more additional malformations including those of the respiratory tract that occur in a relatively high proportion of them and particularly of those with vertebral, anal, cardiac, tracheoesophageal, renal, and limb association. Additionally, a significant proportion of survivors suffer abnormal pulmonary function and chronic respiratory tract disease. The present review summarizes the current knowledge about the nature of these symptoms in patients treated for EA?�?TEF, and explores the hypothesis that disturbed development and maturation of the respiratory tract could contribute to their pathogenesis. PMID:24829898
Fragoso, Ana Catarina; Tovar, Juan A
Adenocarcinoma of the Small Bowel
PURPOSE: Primary small-bowel adenocarcinoma is uncommon. There are few large studies that have evaluated the prognostic impact of clinical and pathologic parameters. The purpose of this study was to perform a comprehensive analysis of the Cleveland Clinic experience with small-bowel adenocarcinoma, with emphasis on histopathologic parameters as prognostic indicators. METHODS: Thirty-seven cases of primary small-bowel adenocarcinomas resected at the Cleveland
Neil A. Abrahams; Amy Halverson; Victor W. Fazio; Lisa A. Rybicki; John R. Goldblum
Recent experience with esophageal atresia.
A nine-year experience with esophageal atresia of all types is described with current diagnostic and therapeutic approaches and long-term results. During this time, 53 neonates with esophageal atresia and tracheoesophageal fistula had a 93% survival, with four deaths in risk group C. Temporary postoperative morbidity related to the anastomosis occurred in ten patients. All patients had some disturbance in esophageal motility. While all have been studied for gastroesophageal reflux, only five had significant reflux, and four required fundoplication. Five patients with isolated esophageal atresia survived staged repair, and an additional five patients with H-type fistulae survived primary repair, including one with a long tracheoesophageal cleft. Despite the fact that 45% of the 63 patients had significant associated anomalies, initial survival was 93.5% and late survival 91%. Long-term functional results were generally satisfactory.
O'Neill, J A; Holcomb, G W; Neblett, W W
Esophageal Cancer - Featured Clinical Trials
Esophageal Cancer - Featured Clinical Trials The following list shows Featured Clinical Trials for a specific type of cancer. You may also want to view: Multiple Cancer Types - Featured Clinical Trials Supportive Care - Featured Clinical Trials Related
Human Esophageal Epithelial Cell Lines.
National Technical Information Service (NTIS)
Human esophageal epithelial cells having replicative capacity in cell culture that is enhanced compared to normal cells and are unable to produce tumors is disclosed. Normal human esophagus tissue from two autopsy specimens was explanted in serum-free med...
G. D. Stoner R. R. Reddel C. C. Harris R. Roger
Esophageal manometry in gastroesophageal reflux disease.
High-resolution manometry (HRM) allows nuanced evaluation of esophageal motor function, and more accurate evaluation of lower esophageal sphincter (LES) function, in comparison with conventional manometry. Pathophysiologic correlates of gastroesophageal reflux disease (GERD) and esophageal peristaltic performance are well addressed by this technique. HRM may alter the surgical decision by assessment of esophageal peristaltic function and exclusion of esophageal outflow obstruction before antireflux surgery. Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve and help predict the likelihood of transit symptoms following antireflux surgery. HRM represents a continuously evolving new technology that compliments the evaluation and management of GERD. PMID:24503360
Mello, Michael; Gyawali, C Prakash
Endoscopic and clinicopathological patterns of esophageal cancer in Tanzania: experiences from two tertiary health institutions
Background Esophageal cancer is one of the most serious gastrointestinal cancer worldwide, owing to its rapid development and fatal prognoses in most cases. There is a paucity of published data regarding esophageal cancer in Tanzania and the study area in particular. This study was conducted to describe the endoscopic and clinicopathological patterns of esophageal cancer in this part of the world. The study provides baseline local data for future comparison. Methods This was a retrospective study of histologically confirmed cases of esophageal cancer seen at Bugando Medical Center and Muhimbili National Hospital between March 2008 and February 2013. Data were retrieved from medical record computer database and analyzed using SPSS computer software version 17.0. Results A total of 328 esophageal cancer patients were enrolled in the study, representing 25.3% of all malignant gastrointestinal tract tumors. The male to female ratio was 2.2:1. The median age of patients at presentation was 47 years. The majority of patients (86.6%) were peasants coming from the rural areas. Smoking and alcohol consumption were documented in 74.7% and 61.6% of patients respectively. Family history of esophageal cancer was reported in 4.6% of cases. The majority of patients (81.7%) presented late with advanced stage of cancer. Progressive dysphagia and weight loss were the most common presenting symptoms occurring in all patients. The middle third esophagus (58.5%) was the most frequent anatomical site for esophageal cancer followed by lower third (27.4%) and upper third esophagus (10.4%). Squamous cell carcinoma (96.0%) was the most common histopathological type. Adenocarcinoma occurred in 13 (4.0%) patients. TNM staging was documented in only 104 (31.7%) patients. Of these, 102(98.1%) patients were diagnosed with advanced esophageal cancer (Stages III and IV). According to tumor grading, most of tumors were moderately differentiated accounting for 56.1% of cases. Distant metastasis was documented in 43.3% of patients. Conclusion Esophageal cancer is not uncommon in this region and shows a trend towards a relative young age at presentation and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations and detecting esophageal cancer at an early stage in order to improve chances for successful treatment and survival.
Steroids in pediatric eosinophilic esophagitis.
Swallowed fluticasone and oral viscous budesonide are effective first-line therapies for eosinophilic esophagitis in children. Side effects are minimal without evidence of Cushing syndrome, as seen in treatment with systemic corticosteroids. New studies on alternative delivery systems and different corticosteroids (eg, ciclesonide) are encouraging. As knowledge of corticosteroids in eosinophilic esophagitis expands, newer questions continue to arise concerning dose, delivery, and choice of corticosteroids; long-term adverse effects; and maintenance therapies. PMID:24813520
Contreras, Emily M; Gupta, Sandeep K
Giant asymptomatic primary esophageal schwannoma.
Primary esophageal schwannomas are uncommon. We describe a case of a large asymptomatic primary esophageal schwannoma in a 65-year-old patient. Computed tomography and positron emission tomography revealed an (18)F-fluorodeoxyglucose-avid 11-cm mass arising from the esophagus. A preoperative diagnosis was made via endoscopic ultrasound. The patient underwent a three-field esophagogastrectomy with cervical esophagogastric anastomosis. He remains well and free of recurrence 10 months after treatment. PMID:22450109
Kassis, Edmund S; Bansal, Shelly; Perrino, Carmen; Walker, Jon P; Hitchcock, Charles; Ross, Patrick; Daniel, Vincent C
Surgical pathology of adenocarcinoma arising in Barrett's esophagus. Analysis of 67 cases.
Numerous reviews of adenocarcinoma arising in Barrett's esophagus have been reported, but detailed pathologic findings or survival analysis have rarely been provided. This retrospective study analyzed 67 patients (mean age, 64 years; male-to-female ratio, 10:1) with an adenocarcinoma arising in Barrett's esophagus treated by surgical resection. Prevalence of smokers was 63%, alcohol users, 45%, and patients with hiatal hernia, 73%. Five patients had another synchronous cancer, and seven patients, previous esophageal surgery. Forty percent of the tumors were well differentiated, 31% moderately differentiated, 15% poorly differentiated, 7% mucinous, and 6% composed of signet-ring cells. Depth of invasion in the esophageal wall was limited to mucosa in 13% of cases and submucosa in 18%. Invasive adenocarcinomas extended to the muscular layer in 12% of cases, to adventitia in 33%, and to periesophageal tissue in 24%. Vascular and perineural neoplastic invasion was present in 67 and 38% of cases. Regional lymph node involvement and distant metastases were found in 51 and 9% of cases. Overall, 1-, 2-, and 5-year survival rates were 63, 41, and 32%, respectively. Five-year survival rate was significantly better for patients with superficial cancer limited to mucosa or submucosa (82 vs. 12%) or without regional lymph node involvement (59 vs. 10%). Tumor differentiation, vascular and perineural invasion, extranodal spread, distant metastases, and resection margins status also had a significant prognostic value on univariate analysis. In a multivariate Cox regression analysis for overall survival, depth of invasion in the esophageal wall and regional lymph node involvement were independent prognostic factors. Careful pathologic staging is of value in determining the prognosis of patients with adenocarcinoma arising in Barrett's esophagus. PMID:7832278
Paraf, F; Fl�jou, J F; Pignon, J P; F�k�t�, F; Potet, F
Hyperthermochemoradiotherapy and esophageal carcinoma
Cancer of the esophagus still poses considerable treatment problems, with a poor 5-year survival rate after surgery, an even worse outlook after radiation and surgery, and a not very satisfactory response to chemotherapy. After several years of continued research, in 1983 we developed a Radio Frequency System with endotract electrode and thermosensors for administering hyperthermochemoradiotherapy to patients with carcinoma of the esophagus. Results in 129 patients are discussed. Immediate improvement of subjective complaints and decrease or elimination of the cancer lesion are so distinct that this treatment, by means of an endotract antenna, shows promise as a modality for esophageal lesions and may find application in diseases such as colorectal cancer or carcinoma of the uterine cervix.
Sugimachi, K.; Inokuchi, K.
The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging
Background In intestinal epithelium, tyrosine kinase receptor Ephrin B3 (Eph B3) maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Eph B3 is linked to colorectal cancer initiation, overexpression of Eph B3 in cancer cell lines inhibits growth and induces functional changes with decreased mesenchymal and increased epithelial markers. In order to study this tumor suppressor activity of Eph B3 in esophageal adenocarcinoma we analyzed the simultaneous expression of Eph B3 and E-cadherin in both the healthy esophagus and in Barrett�s carcinoma. Methods Simultaneous expression of Eph B3 and E-cadherin was investigated in samples from 141 patients with Barrett�s carcinoma and from 20 healthy esophagi using immunhistology and quantitative PCR. Results from healthy squamous epithelium, Barrett�s metaplasia and staging-specific esophageal adenocarcinoma were correlated. Results A significantly reduced E-cadherin mRNA expression could be detected in adenocarcinoma compared to dysplasia. The immunhistological activity of E-cadherin and Eph B3 was reduced in adenocarcinoma compared to dysplasia or healthy esophageal mucosa. The intracellular E-cadherin distribution changed significantly from the cytoplasm to the membrane, when the Eph receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Eph B3 showed a significant inverse correlation to tumor stage. Conclusions We present novel evidence of the tumor suppressor activity of Eph B3 in esophageal adenocarcinoma possibly due to the impact on redistribution of cellular E-cadherin to the membrane. Our results suggest that this effect might play a role in the dysplasia-adenocarcinoma sequence, the infiltrative growth pattern and the development of lymph node metastases.
Esophageal Atresia and Tracheo-Esophageal Fistula -- 25 Years' Experience and Current Management
A review of the experience with esophageal atresia and tracheoesophageal fistula over a 25-year period appears to lead to the advisability of the following procedures in surgical management: � Emergency gastrostomy under local anesthesia in all patients. � Extrapleural interruption of tracheo-esophageal fistula and end-to-end esophago-esophagostomy in patients who have the common type of upper esophageal atresia with distal tracheo-esophageal fistula. � Upper esophageal stretching and eventual esophago-esophagostomy in patients with proximal and distal esophageal atresia with or without proximal tracheo-esophageal fistula. ImagesFigure 1.Figure 2.
Krishinger, G. L.; Woolley, Morton M.
Sucralfate Prevents Experimental Peptic Esophagitis in Rabbits.
National Technical Information Service (NTIS)
Sucralfate was tested in a rabbit model for the ability to prevent experimental esophagitis. Esophagitis was assessed by gross appearance and microscopic examination by an uninformed observer. In addition, the permeability of the esophagus to a number of ...
E. J. Schweitzer B. L. Bass L. F. Johnson J. W. Harmon
Esophageal surgery in newborns, infants and children.
The most common surgery on the esophagus by pediatric surgeons the world over is performed in the newborn period in babies with congenital esophageal atresia with tracheo-esophageal fistula. Post-operative complications like recurrent fistula, anastomotic stricture and some patients with gastroesophageal reflux would also require surgical intervention. Apart from esophageal dilatation, gastrostomy and feeding jejunostomy, children with strictures secondary to caustic ingestion, reflux or previous esophageal anastomosis may require esophageal substitution. This operation may also be required in babies with pure esophageal atresia as well as those with a long gap esophageal atresia with fistula. The entire stomach, stomach tubes, colon or jejunum are often used but techniques preserving as much of the original esophagus as possible are preferable and more physiological. Surgery is also required in children with congenital esophageal stenosis and duplication cyst. PMID:19011807
Menon, Prema; Rao, K L N
21 CFR 878.3610 - Esophageal prosthesis.
Code of Federal Regulations, 2013 CFR
... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal prosthesis. (a) Identification. An esophageal...
MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma
MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2?-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.
Jin, Zhe; Cheng, Yulan; Gao, Yan; Feng, Xianling; Dong, Ming; Cao, Ziyi; Chen, Si; Yu, Huimin; Zhao, Zhenfu; Zhang, Xiaojing; Liu, Jie; Mori, Yuriko; Fan, Xinmin; Meltzer, Stephen J.
Renal Adenocarcinoma in Young Adults
Renal adenocarcinoma is rare in young people. The prognosis of the condition would appear to be better in young people justifying a radical treatment rationale even in cases of advanced disease. This report describes a series of patients under the age of 30 with renal adenocarcinoma and a review of the literature. The possible mechanisms for the apparent improved survival
J. G. Noble; A. M. Parikh; C. R. Chapple; P. H. L. Worth; E. J. G. Milroy
A Comprehensive Review of Esophageal Stents
Esophageal stents are important tools for palliative treatment of inoperable esophageal malignancies. With the development of multiple self-expandable stents, there are now several therapeutic options for managing benign and malignant esophageal diseases. This paper discusses the various types of esophageal stents currently available, indications for their placement, challenges and complications that gastroenterologists face when placing these stents, and some of the innovations that will become available in the near future.
Hong, Jinwha; Lam-Tsai, Yvette; Gress, Frank
New and emerging combination therapies for esophageal cancer
Esophageal cancer comprises two different histological forms � squamous cell carcinoma (SCC) and adenocarcinoma (AC). While the incidence of AC has increased steeply in Western countries during the last few years, the incidence of SCC is fairly stable. Both forms differ in pathogenesis and response to chemotherapy and radiation therapy. Plenty of studies have evaluated new chemotherapy combination regimens in the neoadjuvant, adjuvant, and palliative setting. In addition, new radiation and chemoradiation protocols have been investigated. Finally, molecular-targeted therapy has been included in several new randomized prospective trials. Therefore, this review presents new data on this topic and critically discusses promising approaches towards a more effective treatment in a disease with a grim prognosis.
Wiedmann, Marcus W; Mossner, Joachim
Gallium-67 imaging in candidal esophagitis
Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis.
Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. (Beth Israel Medical Center, New York, NY (USA))
Endoscopic diagnosis of cervical esophageal heterotopic gastric mucosa with conventional and narrow-band images
AIM: To compare the diagnostic yield of heterotopic gastric mucosa (HGM) in the cervical esophagus with conventional imaging (CI) and narrow-band imaging (NBI). METHODS: A prospective study with a total of 760 patients receiving a CI examination (mean age 51.6 years; 47.8% male) and 760 patients undergoing NBI examination (mean age 51.2 years; 45.9% male). The size of HGM was classified as small (1-5 mm), medium (6-10 mm), or large (> 1 cm). A standardized questionnaire was used to obtain demographic characteristics, social habits, and symptoms likely to be related to cervical esophageal HGM, including throat symptoms (globus sensation, hoarseness, sore throat, and cough) and upper esophageal symptoms (dysphagia and odynophagia) at least 3 mo in duration. The clinicopathological classification of cervical esophageal HGM was performed using the proposal by von Rahden et al. RESULTS: Cervical esophageal HGM was found in 36 of 760 (4.7%) and 63 of 760 (8.3%) patients in the CI and NBI groups, respectively (P = 0.007). The NBI mode discovered significantly more small-sized HGM than CI (55% vs 17%; P < 0.0001). For the 99 patients with cervical esophageal HGM, biopsies were performed in 56 patients; 37 (66%) had fundic-type gastric mucosa, and 19 had antral-type mucosa. For the clinicopathological classification, 77 patients (78%) were classified as HGM?I?(asymptomatic carriers); 21 as HGM II (symptomatic without morphologic changes); and one as HGM III (symptomatic with morphologic change). No intraepithelial neoplasia or adenocarcinoma was found. CONCLUSION: NBI endoscopy detects more cervical esophageal HGM than CI does. Fundic-type gastric mucosa constitutes the most common histology. One-fifth of patients have throat or dysphagic symptoms.
Cheng, Chi-Liang; Lin, Cheng-Hui; Liu, Nai-Jen; Tang, Jui-Hsiang; Kuo, Yen-Lin; Tsui, Yi-Ning
The Pathophysiology of Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-? to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.
Raheem, Mayumi; Leach, Steven T.; Day, Andrew S.; Lemberg, Daniel A.
Columnar metaplasia in a surgical mouse model of gastro-esophageal reflux disease is not derived from bone marrow-derived cell.
The incidence of esophageal adenocarcinoma has increased in the last 25 years. Columnar metaplasia in Barrett's mucosa is assumed to be a precancerous lesion for esophageal adenocarcinoma. However, the induction process of Barrett's mucosa is still unknown. To analyze the induction of esophageal columnar metaplasia, we established a mouse gastro-esophageal reflux disease (GERD) model with associated development of columnar metaplasia in the esophagus. C57BL/6 mice received side-to-side anastomosis of the esophagogastric junction with the jejunum, and mice were killed 10, 20, and 40 weeks after operation. To analyze the contribution of bone marrow-derived cells to columnar metaplasia in this surgical GERD model, some mice were transplanted with GFP-marked bone marrow after the operation. Seventy-three percent of the mice (16/22) showed thickened mucosa in esophagus and 41% of mice (9/22) developed columnar metaplasia 40 weeks after the operation with a mortality rate of 4%. Bone marrow-derived cells were not detected in columnar metaplastic epithelia. However, scattered epithelial cells in the thickened squamous epithelia in regions of esophagitis did show bone marrow derivation. The results demonstrate that reflux induced by esophago-jejunostomy in mice leads to the development of columnar metaplasia in the esophagus. However, bone marrow-derived cells do not contribute directly to columnar metaplasia in this mouse model. PMID:23734763
Aikou, Susumu; Aida, Junko; Takubo, Kaiyo; Yamagata, Yukinori; Seto, Yasuyuki; Kaminishi, Michio; Nomura, Sachiyo
Prognostic value of baseline FDG uptake on PET-CT in esophageal carcinoma
AIM: To evaluate the influence of baseline maximum standardized uptake value (SUVmax) on survival in a cohort of patients, undergoing positron emission tomography-computed tomography (PET-CT) scan for esophageal carcinoma. METHODS: The pre-treatment SUVmax numeric reading was determined in patients with confirmed esophageal or junctional cancer having PET-CT scan during the time period 1st January 2007 until 31st July 2012. A minimum follow up of 12 mo was required. Patients were subdivided into quartiles according to SUVmax value and the influence of SUVmax on survival was assessed using univariate and multivariate analysis. The following pre-treatment factors were investigated: patient characteristics, tumor characteristics and planned treatment. RESULTS: The study population was 271 patients (191 male) with esophageal or junctional carcinoma. The median age was 65 years (range 40-85) and histologic subtype was adenocarcinoma in 197 patients and squamous carcinoma in 74 patients. The treatment intent was radical in 182 and palliative in 89 patients. SUVmax was linked to histologic subtype (P = 0.008), tumor site (P = 0.01) and Union for International Cancer Control (UICC) stage (P < 0.001). On univariate analysis, prognosis was significantly associated with SUVmax (P = 0.001), T-stage (P < 0.001) and UICC stage (P < 0.001). On multivariate analysis, only T-stage and UICC stage remained significant. CONCLUSION: Pretreatment SUVmax was not a useful marker in isolation for determining prognosis of patients with esophageal carcinoma.
Al-Taan, Omar S; Eltweri, Amar; Sharpe, David; Rodgers, Peter M; Ubhi, Sukhbir S; Bowrey, David J
Deoxycholic acid impairs glycosylation and fucosylation processes in esophageal epithelial cells.
It is generally accepted that esophageal adenocarcinoma arises from a Barrett's metaplastic lesion. Altered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown. The bile acid deoxycholic acid (DCA) alters many cell signaling pathways and is implicated in esophageal cancer progression. We have demonstrated that DCA disrupts Golgi structure and affects protein secretion and glycosylation processes in cell lines derived from normal squamous epithelium (HET-1A) and Barrett's metaplastic epithelium (QH). Cell surface expression of glycans was identified using carbohydrate-specific probes (wheat germ agglutinate, conconavalin A, peanut agglutinin, lithocholic acid and Ulex europaeus agglutinin) that monitored N-glycosylation, O-glycosylation and core fucosylation in resting and DCA-treated cells. DCA altered intracellular localization and reduced cell surface expression of N-acetyl-D-glucosamine, ?-methyl-mannopyranoside (Man/Glc) and fucose in both cell lines. Furthermore, DCA reduced the expression of epithelial growth factor receptor and E-cadherin in a manner analogous to treatment of cells with the N-glycan biosynthesis inhibitor tunicamycin. This is the first study to identify an altered Golgi structure and glycomic profile in response to DCA in esophageal epithelial cells, a process which could potentially contribute to metaplasia, dysplasia and cancer of the esophagus. PMID:22223758
Byrne, Anne-Marie; Sharma, Ruchika; Duggan, Gina; Kelleher, Dermot; Long, Aideen
Therapeutic and Radiosensitizing Effects of Armillaridin on Human Esophageal Cancer Cells
Background. Armillaridin (AM) is isolated from Armillaria mellea. We examined the anticancer activity and radiosensitizing effect on human esophageal cancer cells. Methods. Human squamous cell carcinoma (CE81T/VGH and TE-2) and adenocarcinoma (BE-3 and SKGT-4) cell lines were cultured. The MTT assay was used for cell viability. The cell cycle was analyzed using propidium iodide staining. Mitochondrial transmembrane potential was measured by DiOC6(3) staining. The colony formation assay was performed for estimation of the radiation surviving fraction. Human CE81T/VGH xenografts were established for evaluation of therapeutic activity in vivo. Results. AM inhibited the viability of four human esophageal cancer cell lines with an estimated concentration of 50% inhibition (IC50) which was 3.4�6.9??M. AM induced a hypoploid cell population and morphological alterations typical of apoptosis in cells. This apoptosis induction was accompanied by a reduction of mitochondrial transmembrane potential. AM accumulated cell cycle at G2/M phase and enhanced the radiosensitivity in CE81T/VGH cells. In vivo, AM inhibited the growth of CE81T/VGH xenografts without significant impact on body weight and white blood cell counts. Conclusion. Armillaridin could inhibit growth and enhance radiosensitivity of human esophageal cancer cells. There might be potential to integrate AM with radiotherapy for esophageal cancer treatment.
Chi, Chih-Wen; Chen, Chien-Chih; Chen, Yu-Jen
Risks of Esophageal Cancer Screening
... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... adenocarcinoma each year and fewer new cases of squamous cell carcinoma. Squamous cell carcinoma of the esophagus is found ...
Treatment strategy and long-term prognosis for patients with esophageal atresia and congenital heart diseases.
A review examined six consecutive cases of patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) who underwent cardiac surgery at the authors' institution between 2001 and 2011 for associated complex congenital heart diseases. All the patients had a normal karyotype and showed EA with distal TEF. In all cases, gastrostomy was the initial surgical intervention. Cardiac surgery was performed concurrently with gastrostomy for one patient who had a total anomalous pulmonary venous connection with pulmonary venous obstruction. For two patients with duct-dependent pulmonary circulation, EA/TEF was corrected in the neonatal period, and an aortopulmonary shunt operation was electively performed after the first month of life. For two patients with duct-dependent systemic circulation, repair of EA/TEF was performed concurrently with gastrostomy, followed by palliative cardiac surgery during the neonatal period. For another patient without duct-dependent circulation, repair of EA/TEF was performed in the neonatal period. No mortality occurred during a median follow-up period of 6.2�years. However, respiratory complications including severe tracheomalacia for two patients, recurrent episodes of respiratory infection for three patients, and severe gastroesophageal reflux for five patients caused considerable long-term morbidity. PMID:22639007
Hayashi, Taiyu; Inuzuka, Ryo; Shiozawa, Yusuke; Shindo, Takahiro; Shimizu, Nobutaka; Katori, Tatsuo
Airway responses to esophageal acidification.
The effects of esophageal acidification on airway function are unclear. Some have found that the esophageal acidification causes a small increase in airway resistance, but this change is too small to cause significant symptoms. The aims of this study were to investigate the effects of esophageal acidification on multiple measures of airway function in chloralose-anesthetized cats. The esophagus was cannulated and perfused with either 0.1 M PBS or 0.1 N HCl at 1 ml/min as the following parameters were quantified in separate experiments: diameter of bronchi (n = 5), tracheal mucociliary transport rate (n = 4), tracheobronchial mucus secretion (n = 7), and lung function (n = 6). We found that esophageal acidification for 10-30 min decreased bronchial diameters primarily of the smaller low-resistance airways (10-22%, P < 0.05), decreased tracheal mucociliary transport (53%, 8.7 +/- 2.4 vs. 4.1 +/- 1.3 mm/min, P < 0.05), increased tracheobronchial mucus secretion (147%, 3.4 +/- 0.7 vs. 8.4 +/- 2.6 mg/10 min, P < 0.05), and caused no change in total lung resistance or dynamic compliance (P > 0.05). Considering that tracheal mucociliary transport rate is governed in part by mucus secretion, we concluded that the primary airway response to esophageal acidification observed is increased mucus secretion. Airway constriction may act to assist in rapid secretion of mucus and to increase the effectiveness of coughing while not affecting lung resistance or compliance. Given the buffering capabilities of mucus, esophageal acidification activates appropriate physiological responses that may act to neutralize gastroesophageal reflux that reaches the larynx, pharynx, or lower airways. PMID:17928508
Lang, Ivan M; Haworth, Steven T; Medda, Bidyut K; Roerig, David L; Forster, Hubert V; Shaker, Reza
Code of Federal Regulations, 2012 CFR
...COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements ...indicates the geographic area affected by the EAS alert. There may be 31 Location codes in an EAS alert. The Location code uses the codes...
Code of Federal Regulations, 2011 CFR
...COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements ...indicates the geographic area affected by the EAS alert. There may be 31 Location codes in an EAS alert. The Location code uses the...
Code of Federal Regulations, 2013 CFR
...COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements ...indicates the geographic area affected by the EAS alert. There may be 31 Location codes in an EAS alert. The Location code uses the codes...
Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma.
The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. PMID:16331610
Kang, Sokbom; Kim, Jae Weon; Kang, Gyeong Hoon; Lee, Sun; Park, Noh Hyun; Song, Yong Sang; Park, Sang Yoon; Kang, Soon Beom; Lee, Hyo Pyo
Biological identification of ampullary adenocarcinomas.
Ampullary adenocarcinomas have unique biologic and clinical features that result in its improved prognosis versus adenocarcinomas that arise from the distal bile ducts and pancreas. However the histological differentiation and identification of these tumors is not easily accomplished. Two abstracts at this year's ASCO Annual Meeting describe attempts to identify unique methods for distinguishing these tumors. Abstract #4141 described a 92 gene RT-PCR assay that was used for molecular classification of patients with ampullary adenocarcinomas while Abstract #e15175 looked at mutational status of K-ras in patients with these tumors. The results of their abstracts will be discussed. PMID:25076327
Relias, Valerie; Saif, Muhammad Wasif
Dietary treatment of eosinophilic esophagitis.
Emerging evidence supports impaired epithelial barrier function as the key initial event in the development of eosinophilic esophagitis (EoE) and other allergic diseases. Symptom resolution, histologic remission, and prevention of both disease and treatment-related complications are the goals of treatment. Successful dietary treatments include elemental, empirical elimination and allergy test directed diets. Dietary therapy with exclusive elemental diet offers the best response. Cow's milk, wheat, egg, soy, peanut/tree nut, and fish/shellfish are the 6 food antigens most likely to induce esophageal inflammation. PMID:24813522
Gonsalves, Nirmala; Kagalwalla, Amir F
Preoperative Cetuximab, Irinotecan, Cisplatin, and Radiation Therapy for Patients With Locally Advanced Esophageal Cancer
Purpose. To determine the efficacy and toxicity of weekly neoadjuvant cetuximab combined with irinotecan, cisplatin, and radiation therapy in patients with locally advanced esophageal or gastroesophageal junction cancer. Methods and Materials. Patients with stage IIA�IVA esophageal or gastroesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received weekly cetuximab on weeks 0�8 and irinotecan and cisplatin on weeks 1, 2, 4, and 5, with concurrent radiotherapy (50.4 Gy on weeks 1�6), followed by surgical resection. Results. In the first stage, 17 patients were enrolled, 16 of whom had adenocarcinoma. Because of a low pathologic complete response (pCR) rate in this cohort, the trial was discontinued for patients with adenocarcinoma but squamous cell carcinoma patients continued to be enrolled; two additional patients were enrolled before the study was closed as a result of poor accrual. Of the 19 patients enrolled, 18 patients proceeded to surgery, and 16 patients underwent an R0 resection. Three patients (16%) had a pCR. The median progression-free survival interval was 10 months, and the median overall survival duration was 31 months. Severe neutropenia occurred in 47% of patients, and severe diarrhea occurred in 47% of patients. One patient died preoperatively from sepsis, and one patient died prior to hospital discharge following surgical resection. Conclusions. This schedule of cetuximab in combination with irinotecan, cisplatin, and radiation therapy was toxic and did not achieve a sufficient pCR rate in patients with localized esophageal adenocarcinoma to undergo further evaluation.
Lee, Michael S.; Mamon, Harvey J.; Hong, Theodore S.; Choi, Noah C.; Fidias, Panagiotis M.; Kwak, Eunice L.; Meyerhardt, Jeffrey A.; Ryan, David P.; Bueno, Raphael; Donahue, Dean M.; Jaklitsch, Michael T.; Lanuti, Michael; Rattner, David W.; Fuchs, Charles S.
Gastroesophageal Reflux Disease Symptom Severity, Proton Pump Inhibitor Use, and Esophageal Carcinogenesis
Hypothesis Screening for esophageal adenocarcinoma has focused on identifying Barrett esophagus (BE) in patients with severe, long-standing symptoms of gastroesophageal reflux disease(GERD). Unfortunately, 95%of patients who develop esophageal adenocarcinoma are unaware of the presence of BE before their cancer diagnosis, which means they never had been selected for screening. One possible explanation is that no correlation exists between the severity of GERD symptoms and cancer risk. We hypothesize that severe GERD symptoms are not associated with an increase in the prevalence of BE, dysplasia, or cancer in patients undergoing primary endoscopic screening. Design Cross-sectional study. Setting University hospital. Patients A total of 769 patients with GERD. Interventions Primary screening endoscopy performed from November 1, 2004, through June 7, 2007. Main Outcomes Measures Symptom severity, proton pump inhibitor therapy, and esophageal adenocarcinogenesis (ie, BE, dysplasia, or cancer). Results Endoscopy revealed adenocarcinogenesis in 122 patients. An increasing number of severe GERD symptoms correlated positively with endoscopic findings of esophagitis (odds ratio, 1.05; 95% confidence interval, 1.01-1.09). Conversely, an increasing number of severe GERD symptoms were associated with decreased odds of adenocarcinogenesis (odds ratio, 0.94; 95% confidence interval, 0.89-0.98). Patients taking proton pump inhibitors were 61.3% and 81.5% more likely to have adenocarcinogenesis if they reported no severe typical or atypical GERD symptoms, respectively, compared with patients taking proton pump inhibitors, who reported that all symptoms were severe. Conclusions Medically treated patients with mild or absent GERD symptoms have significantly higher odds of adenocarcinogenesis compared with medically treated patients with severe GERD symptoms. This finding may explain the failure of the current screening paradigm in which the threshold for primary endoscopic examination is based on symptom severity.
Nason, Katie S.; Wichienkuer, Promporn Paula; Awais, Omar; Schuchert, Matthew J.; Luketich, James D.; O'Rourke, Robert W.; Hunter, John G.; Morris, Cynthia D.; Jobe, Blair A.
Analysis of thermal effects in endoscopic nanocarriers-based photodynamic therapy applied to esophageal diseases
NASA Astrophysics Data System (ADS)
In this work we propose a predictive model that allows the study of thermal effects produced when the optical radiation interacts with an esophageal or stomach disease with gold nanoparticles embedded. The model takes into account light distribution in the tumor tissue by means of a Monte Carlo method. Mie theory is used to obtain the gold nanoparticles optical properties and the thermal model employed is based on the bio-heat equation. The complete model was applied to two types of tumoral tissue (squamous cell carcinoma located in the esophagus and adenocarcinoma in the stomach) in order to study the thermal effects induced by the inclusion of gold nanoparticles.
Salas-Garc�a, I.; Fanjul-V�lez, F.; Ortega-Quijano, N.; Wilfert, O.; Hudcova, L.; Poliak, J.; Barcik, P.; Arce-Diego, J. L.
Study finds molecular 'signature' for rapidly increasing form of esophageal cancer
During the past 30 years, the number of patients with cancers that originate near the junction of the esophagus and stomach has increased approximately 600 percent in the United States. The first extensive probe of the DNA of these esophageal adenocarcinomas (EACs) has revealed that many share a distinctive mix-up of letters of the genetic code, and found more than 20 mutated genes that had not previously been linked to the disease. The research, led by scientists at Dana-Farber Cancer Institute, the Broad Institute, and other research centers, may offer clues to why EAC rates have risen so sharply.
Esophageal dilations in eosinophilic esophagitis: A single center experience
AIM: To diagnose the clinical and histologic features that may be associated with or predictive of the need for dilation and dilation related complications; examine the safety of dilation in patients with eosinophilic esophagitis (EoE). METHODS: The medical records of all patients diagnosed with EoE between January 2002 and July 2010 were retrospectively reviewed. Esophageal biopsies were reexamined by an experienced pathologist to confirm the diagnosis (? 15 eos/hpf per current guidelines). Patients were divided into 2 groups: patients who did not receive dilation therapy and those who did. Demographics, clinical history, the use of pharmacologic therapy, endoscopic and pathology findings, and the number of biopsies and dilations carried out, if any, and their locations were recorded for each patient. The dilation group was further examined based on the interval between diagnosis and dilation, and whether or not a complication occurred. RESULTS: Sixty-one patients were identified with EoE and 22 (36%) of them underwent esophageal dilations for stricture/narrowing. The peak eos/hpf was significantly higher in patients who received a dilation (P = 0.04). Four (18% of pts.) minor complications occurred: deep mucosal tear 1, and small mucosal tears 3. There were no cases of esophageal perforations. Higher peak eos/hpf counts were not associated with increased risk of complications. CONCLUSION: Esophageal dilation appears to be a safe procedure in EoE patients, carrying a low complication rate. No correlation was found between the peak of eosinophil count and complication rate. Complications can occur independently of the histologic features. The long-term outcome of EoE treatment, with or without dilation, needs to be determined.
Ukleja, Andrew; Shiroky, Jennifer; Agarwal, Amitesh; Allende, Daniela
Pancreatic adenocarcinoma: epidemiology and genetics.
Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. There are few established environmental risk factors, but a previous history of pancreatitis and exposure to tobacco and salted food appear to be the most important. A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that pancreatic adenocarcinoma can be a feature of cancer susceptibility syndromes associated with germline mutations in p16, BRCA1, BRCA2, and APC. This highlights the need for a full family history in apparently sporadic cases. Somatic mutations in p16, BRCA2, and APC have also been reported in pancreatic cancer; however, K-RAS mutations appear to be the commonest oncogenic alteration. Recent advances in our understanding of the basis of hereditary cancer syndromes may be applicable to the diagnosis, treatment, and possibly prevention of pancreatic adenocarcinoma in the future.
Flanders, T Y; Foulkes, W D
Extended Resection for Pancreatic Adenocarcinoma
Adenocarcinoma of the pancreas presents a number of therapeutic challenges. Given the poor long-term out- comes after pancreaticoduodenectomy (PD), many sur- geons have sought to improve survival via a radical or \\
Functional Gastrointestinal Disorders Induced by Esophageal Atresia Surgery: Is It Valid in Humans?
Background/Aims Functional gastrointestinal disorders (FGID) affect 15%-20% of the general pediatric and adult population. Animal models suggest that a neonatal stress such as invasive procedures and maternal separation could be responsible for visceral hypersensitivity and FGID. We tested the hypothesis that congenital esophageal atresia (EA), a condition corrected during the neonatal period and associated with multiple stresses, is a clinically significant risk factor for the development of FGID later in life. We postulated that, to be clinically significant, the effect of neonatal stress on the incidence of FGID should be as strong as that of enteric infections in the development of irritable bowel syndrome in children. Methods Subjects with EA and healthy controls were enrolled in this multicenter cohort study. Gastrointestinal symptoms were assessed by a questionnaire and FGID was diagnosed using the Rome III criteria. Results Fifty-three children (25 girls; median age, 12 years) with EA were compared to 72 age- and sex-matched controls. Although 11 children with EA (21%) had a FGID diagnosis versus 8 controls (11%), this difference was not significant (?2 = 2.20, P > 0.05). In subjects with EA, the presence of associated malformations, the occurrence of complications during the first month, and the length of hospital stay > 30 days did not influence the incidence of FGID. Chronic abdominal pain was present in 38% of subjects with EA versus 25% of controls (P > 0.05). Conclusions Neonatal stress secondary to surgical correction of EA is not a clinically significant risk factor for the development of FGID in childhood.
Revillion, Marine; Michaud, Laurent; Gottrand, Frederic; Faure, Christophe
Renal adenocarcinoma in young adults.
Renal adenocarcinoma is rare in young people. The prognosis of the condition would appear to be better in young people justifying a radical treatment rationale even in cases of advanced disease. This report describes a series of patients under the age of 30 with renal adenocarcinoma and a review of the literature. The possible mechanisms for the apparent improved survival of patients in this age group is discussed. PMID:7974885
Noble, J G; Parikh, A M; Chapple, C R; Worth, P H; Milroy, E J
Esophageal motility in the elderly
The effect of age on motor function of the esophagus was studied manometrically by comparing 49 asymptomatic subjects over 60 years of age with 43 similar subjects under 40 years of age. The resting pressures and the responses to deglutition were recorded in the esophagus, lower esophageal sphincter (LES), and the stomach. Significant differences in motility patterns were seen between
T. Ali Khan; B. W. Shragge; J. S. Crispin; J. F. Lind
Achalasia and Esophageal Motility Disorders
... that is visible under x-rays, creating a picture of the lining of the esophagus and stomach. Discoordinated muscular activity within the esophagus can sometimes be seen using this test. One of the best tests to evaluate for achalasia and other esophageal ...
Esophageal atresia: Factors influencing survival - Experience at an Indian tertiary centre
Objective: To study the clinical profile of the cases of esophageal atresia (EA) and/or tracheoesophageal fistula (TEF) and various factors affecting the surgical and early postoperative management and their outcome. Materials and Methods: A prospective analysis of 127 cases of EA from February 2004 to May 2006 was performed. Waterston prognostic criteria were used for grading. Results: EA with TEF was the commonest type in 117 cases (92%). Associated congenital anomalies were present in 52 (41%) patients, the commonest being the cardiac anomalies, which was followed by the gastrointestinal anomalies. VACTERL was found in 6 (5%) cases. Prematurity, associated congenital anomalies, gap between esophageal ends and preoperative respiratory status were the significant factors affecting the survival (P = < 0.001). Primary extrapleural repair was the surgical approach in most of the patients. Azygos vein was preserved in 46 cases and no retropleural drainage was used in 27 cases. Staged procedures were performed in 19 cases, including 6 cases of isolated esophageal atresia. Pneumonitis and sepsis were the most common early postoperative complications (42%). Hypoxia and cardiorespiratory arrest were the most common causes of mortality (11 cases). Anastomotic leak complicated 13 cases, including 9 major and 4 minor leaks. Major leak followed by sepsis caused 7 deaths. Survival as per Waterston criteria was 100% in group A, 83% in group B and 22% in group C. Conclusion Factors affecting the survival are major or life-threatening associated anomalies, long gap, pneumonia and sepsis at presentation or that acquired during hospitalization and major leaks. The high incidence of low birth weight, delayed diagnosis, poor referral, low-socio economic status and lack of advanced neonatological back up are important contributory factors to poor outcome.
Tandon, R. K.; Sharma, Satendra; Sinha, Shandip K.; Rashid, Kumar Abdul; Dube, Ravi; Kureel, S. N.; Wakhlu, Ashish; Rawat, J. D.
Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer
Purpose: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center. Methods and Materials: This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test. Results: The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups. Conclusions: This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.
Lin, Steven H., E-mail: email@example.com [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Myles, Bevan [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guo Xiaomao [Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Palmer, Matthew [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G.; Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
FAP related periampullary adenocarcinoma
INTRODUCTION The risk of periampullary neoplasia in patients with familial adenomatous polyposis (FAP) is significantly increased compared to the general population. PRESENTATION OF CASE We herein report the case of a 47-year-old woman with classic familial adenomatous polyposis with a history of total proctocolectomy for FAP who presented with an ulcerous ampullary lesion 8 years after primary colorectal surgery. Interestingly, the patient had not enrolled to optimal postoperative upper endoscopy follow-up. The patient underwent a Whipple procedure. Histology demonstrated a T2N0 ampullary adenocarcinoma. DISCUSSION Periampullary disease in patients with familial adenomatous polyposis occurs increasingly, especially in the subset of patients without proper endoscopic follow-up. Current recommendations concerning upper endoscopy and appropriate management are herein discussed; the importance of optimal postoperative endoscopy after total proctocolectomy in the FAP setting is discussed. CONCLUSION Periampullary cancer carries a significant risk in patients with FAP and proper endoscopic follow-up should be applied in this special patient group in order to manage ampullary manifestations of the disease in a timely manner.
Mantas, Dimitrios; Charalampoudis, Petros; Nikiteas, Nikolaos
Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer
Background The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. Methods The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. Results Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. Conclusion Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations.
Tan, Duan-Jun; Chang, Julia; Liu, Ling-Ling; Bai, Ren-Kui; Wang, Yu-Fen; Yeh, Kun-Tu; Wong, Lee-Jun C
Gamma knife radiosurgery for management of cerebral metastases from esophageal carcinoma.
Esophageal carcinoma rarely results in intracranial metastases but when it does, the patient prognosis is grim. Because of its rarity outcomes after stereotactic radiosurgery (SRS) are not known. We sought to evaluate the outcomes of SRS in the management of esophageal cancer that has spread to the brain. This single institution retrospective analysis reviewed our experience with esophageal metastasis from 1987 to 2013. Thirty patients (36 SRS procedures) with a median age of 59 (37-86�years) underwent Gamma knife(�) SRS. The esophageal origin was adenocarcinoma in 26 patients (87�%), squamous cell carcinoma in 3 patients (10�%), and mixed neuroendocrine carcinoma in 1 patient (3�%). Fifteen patients were treated for a single metastasis and 15 patients were treated for multiple metastases for a total of 87 tumors. The median tumor volume was 5.7�cm(3) (0.5-44�cm(3)) with a median marginal dose of 17�Gy (12-20�Gy). The median survival time from the diagnosis of brain metastasis was 8�months and the median survival from SRS was 4.2�months. This corresponded to a 6-month survival of 45�% and a 12-month survival of 19�% after SRS. A higher KPS at the time of procedure was associated with an increase in survival (p�=�0.023). The local tumor control rate in this group was 92�%. Four patients had repeat SRS for new metastatic deposits. One patient developed a new neurological deficit after SRS. SRS proved an effective means of providing local control for esophageal metastases to the brain. Concomitant systemic disease progression at the time of brain metastasis resulted in poor long-term survival. PMID:24736828
Bowden, Greg; Kano, Hideyuki; Tempel, Zachary J; Caparosa, Ellen; Monaco, Edward; Niranjan, Ajay; Flickinger, John; Luketich, James D; Lunsford, L Dade
Human Esophageal Cancer Is Distinguished from Adjacent Esophageal Tissue by Tissue Cysteine Concentrations
Recent studies have suggested that cysteine, in addition to glutathione, may play a role in the genesis, pathobiology, and treatment response of rodent and human cancers. We examined the relative concentrations of cysteine and glutathione in human esophageal cancer and adjacent, minimally involved esophageal tissue. Small biopsies from tumors and adjacent esophageal tissues were placed into cold acid to allow
S. M. Evans; R. Lew; M. L. Kochman; E. P. Wileyto; E. Baum; K. M. Safford; C. J. Koch
Adenosine-induced activation of esophageal nociceptors
Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A1 receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A1 and/or A2A receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A1 receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A2A receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A1 receptor while the placodes-derived esophageal nociceptors can be activated via A1 and/or A2A receptors. Direct activation of esophageal nociceptors via adenosine receptors may contribute to the symptoms in esophageal diseases.
Ru, F.; Surdenikova, L.; Brozmanova, M.
Surgical treatment of superficial esophageal cancer
Objective��The worldwide incidence of superficial esophageal cancer (SEC) is increasing. The aim of this study is to review the systematic surgical outcomes of esophagectomy for SEC.Data sources��Only manuscripts written in English and written between 1980 and 2003 were selected from MEDLINE. The keywords consisting of superficial esophageal cancer, early esophageal cancer, and early stage or superficial stage or stage I
Mitsuo Tachibana; Shoichi Kinugasa; Muneaki Shibakita; Yasuhito Tonomoto; Shinji Hattori; Ryoji Hyakudomi; Hiroshi Yoshimura; Dipok Kumar Dhar; Naofumi Nagasue
Esophageal mesenchymal tumors: Endoscopy, pathology and immunohistochemistry
AIM: To study the endoscopic, pathological and immuno-histochemical features of esophageal mesenchymal tumors. METHODS: Twenty-nine patients diagnosed as esophageal mysenchymal tumors by electronic endoscopy and endoscopic ultrasound (EUS) were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS: Endoscopically, esophageal gastrointestinal stromal tumors (GISTs) and leiomyomas (LMs) had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells: spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcomas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher�s exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 (P > 0.05). All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 (P < 0.005). All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 1/5 (P < 0.005). CONCLUSION: The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.
Zhu, Xuan; Zhang, Xiao-Qian; Li, Bi-Min; Xu, Ping; Zhang, Kun-He; Chen, Jiang
Esophageal motility abnormalities in gastroesophageal reflux disease
Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett�s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.
Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo
Anatomy and physiology of the esophageal body.
The primary role of the esophagus is to propel swallowed food or fluid into the stomach and to prevent or clear gastroesophageal reflux. This function is achieved by an organized pattern that involves a sensory pathway, neural reflexes, and a motor response that includes esophageal tone, peristalsis, and shortening. The motor function of the esophagus is controlled by highly complex voluntary and involuntary mechanisms. There are three different functional areas in the esophagus: the upper esophageal sphincter, the esophageal body, and the LES. This article focused on anatomy and physiology of the esophageal body. PMID:21385283
Yazaki, E; Sifrim, D
The esophageal coin: is it a penny?
Because of their high zinc content modern U.S. pennies that become lodged in the esophagus may react with stomach acid thereby damaging the esophageal mucosa. Management of esophageal pennies may therefore differ from that of other esophageal coins making differentiation of pennies from other coins important. We reviewed the records of 111 children who underwent endoscopic esophageal coin removal over a 19-year period to determine the ability of history and size of esophageal coin images on posterior-anterior and lateral chest radiographs alone and in combination to differentiate esophageal pennies from other esophageal coins. History alone accurately identified 83 per cent of esophageal coins. Ranges of two standard deviations around mean image sizes were determined for each coin denominations. We determined the probability of an esophageal coin being a penny based on combinations of historical data and whether or not image sizes fell within the calculated range for a penny. When all data agree that a coin is or is not a penny they are nearly always correct. When there is disagreement among historical and image size data the probability that is a coin is a penny is strongly influenced by the size of the radiographic images. PMID:12013283
Cantu, Santos; Conners, Gregory P
De Novo Deletion of Chromosome 20q13.33 in a Patient with Tracheo-esophageal Fistula, Cardiac Defects and Genitourinary Anomalies Implicates GTPBP5 as a Candidate Gene
BACKGROUND Tracheo-esophageal fistula (TEF) with/or without esophageal atresia (EA) is a common congenital malformation that is often accompanied by other anomalies. The causes of this condition are thought to be heterogeneous but are overall not well understood. CASE REPORT We identified a patient with a TEF/EA, as well as cardiac and genitourinary anomalies, who was found to have a 0.7 Mb de novo deletion of chromosome 20q13.33. One gene within the deleted interval, GTPBP5, is of particular interest as a candidate gene. CONCLUSIONS GTPBP5 bears further study as a cause of TEF/EA accompanied by other malformations. Birth Defects Research (Part A) 2011. � 2011 Wiley-Liss, Inc.
Solomon, Benjamin D; Pineda-Alvarez, Daniel E; Hadley, Donald W; Keaton, Amelia A; Agochukwu, Nneamaka B; Raam, Manu S; Carlson-Donohoe, Hannah E; Kamat, Aparna; Chandrasekharappa, Settara C
EA Shuttle Document Retention Effort
NASA Technical Reports Server (NTRS)
This slide presentation reviews the effort of code EA at Johnson Space Center (JSC) to identify and acquire databases and documents from the space shuttle program that are adjudged important for retention after the retirement of the space shuttle.
Wagner, Howard A.
Risk factors for eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a chronic antigen driven disease, whereby food and/or aeroallergens result in inflammation and luminal narrowing, and the clinical symptoms of dysphagia and food bolus obstruction events (FBOE). Established risk factors are male gender, Caucasian race and atopy. Increased risk amongst family members, and a single nucleotide polymorphism (SNP) in a gene coding thymic stromal lymphopoietin (TSLP) on the pseudoautosomal region of the X and Y chromosomes supports a genetic predisposition. Environmental factors including the timing and nature of food and aeroallergen exposure to the developing immune system may be important, whilst esophageal barrier function integrity and the influence of microbiota are worthy of future research. PMID:24990069
Philpott, H; Nandurkar, S; Royce, S G; Thien, F; Gibson, P R
Unusual presentation of metastatic adenocarcinoma
Background The most common tumours of the adrenal gland are adenoma, pheochromocytoma, adrenocortical carcinoma, and metastases. Although the imaging features of these tumours are established, the imaging characteristics of uncommon adrenal masses are less well known. In patients with extradrenal tumour, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy. Case presentation A 52 year-old female was diagnosed with oesophageal adenocarcinoma and treated with oesophagectomy and adjuvant chemotherapy. Sixteen months later on staging CT scan a 2 � 2 cm adrenal mass was detected, which increased in size over a period of time to 3 � 3 cm in size. Adrenalectomy was performed and histological examination revealed metastatic adenocarcinoma within an adrenal adenoma. Conclusion The present case highlights the unusual behaviour of an oesophageal adenocarcinoma causing metastasis to an adrenocortical adenoma.
Bagwan, Izhar N; Cook, Gary; Mudan, Satvinder; Wotherspoon, Andrew
Endoscopic Detection of Esophageal Neoplasia
Endoscopic visualization of the esophagus has been practiced since the 19th century; the first illuminated views were obtained\\u000a by Mikulicz in 1880 (1). Esophagogastroduodenoscopy (EGD) or �upper endoscopy� is one of the most frequently performed semi-invasive procedures,\\u000a currently accounting for approx 25% of all endoscopies conducted annually. Use of endoscopy to detect esophageal dysplasia\\u000a in the United States is primarily
Brian C. Jacobson; Jacques Van Dam
Esophageal schwannoma: a case report.
Most tumorous lesions of the esophagus are esophageal cancers. Benign primary tumors of the esophagus are uncommon, and account for approximately 2% of all esophageal tumors. More than 80% of benign esophageal tumors are leiomyomas, with schwannomas being rare. A 55-year-old woman visited our internal medicine department with complaints of palpitations and discomfort during swallowing. A chest computed tomography scan showed a lobulated tumor (75 � 57 � 80 mm) in the upper to middle mediastinum, with homogenous inner opacity, compressing the esophagus. Upper gastrointestinal endoscopy revealed a smooth-surfaced elevated lesion covered with normal mucosa, and a schwannoma was diagnosed based on the biopsy result. The tumor was large. It was thus considered to be difficult to repair the esophagus by direct anastomosis after tumor resection. Therefore, subtotal esophagectomy and esophagogastrostomy in the right thorax were performed. Histopathological examination revealed spindle-shaped cells in a fasciculated and disarrayed architecture and nuclei in a palisading pattern. Immunohistochemical studies revealed S100 protein positivity and the absence of staining for ? smooth muscle actin (?SMA), CD34 and CD117, thereby establishing the diagnosis of benign schwannoma. Her postoperative course was uneventful and there has been no evidence of recurrence to date. PMID:24088647
Kitada, Masahiro; Matsuda, Yoshinari; Hayashi, Satoshi; Ishibashi, Kei; Oikawa, Kensuke; Miyokawa, Naoyuki
Darier's disease with esophageal carcinoma.
We report a patient with longstanding Darier's disease (DD) involving the mucous membrane of the esophagus who developed esophageal carcinoma. A number of small white plaques were observed around the carcinoma in the postoperative specimens of the esophageal mucosal epithelium. Histopathological findings of the specimens near the carcinoma showed suprabasal clefts and villi formation, features consistent with DD, with no evidence of malignancy. There was some speculation on the pathogenic relationship between esophageal carcinoma and DD in this patient, but nothing was confirmed. Immunohistochemistry of lesional skin examined with antibody against desmogleins (Dsgs) 1 + 2 showed a diffuse pattern throughout the cytoplasm in most of the suprabasal acantholytic cells, whereas some of the spherical acantholytic cells showed a ring pattern surrounding the nucleus. In electron microscopy, these areas stained with Dsgs corresponded to dispersed tonofibrils in the suprabasal acantholytic cells and perinuclear aggregation of tonofibrils in the spherical acantholytic cells. This implies that in DD patients, some affinity remains after acantholysis between Dsgs and intermediate filaments, possibly through other desmosomal components. PMID:10980472
Shimizu, H; Tan Kinoshita, M T; Suzuki, H
Novel Device to Sample the Esophageal Microbiome--The Esophageal String Test
A growing number of studies implicate the microbiome in the pathogenesis of intestinal inflammation. Previous work has shown that adults with esophagitis related to gastroesophageal reflux disease have altered esophageal microbiota compared to those who do not have esophagitis. In these studies, sampling of the esophageal microbiome was accomplished by isolating DNA from esophageal biopsies obtained at the time of upper endoscopy. The aim of the current study was to identify the esophageal microbiome in pediatric individuals with normal esophageal mucosa using a minimally invasive, capsule-based string technology, the Enterotest�. We used the proximal segment of the Enterotest string to sample the esophagus, and term this the �Esophageal String Test� (EST). We hypothesized that the less invasive EST would capture mucosal adherent bacteria present in the esophagus in a similar fashion as mucosal biopsy. EST samples and mucosal biopsies were collected from children with no esophageal inflammation (n?=?15) and their microbiome composition determined by 16S rRNA gene sequencing. Microbiota from esophageal biopsies and ESTs produced nearly identical profiles of bacterial genera and were different from the bacterial contents of samples collected from the nasal and oral cavity. We conclude that the minimally invasive EST can serve as a useful device for study of the esophageal microbiome.
Wagner, Brandie D.; Kelly, Caleb J.; Stevens, Mark J.; Moore, Wendy; Fang, Rui; Schroeder, Shauna; Masterson, Joanne C.; Robertson, Charles E.; Pace, Norman R.; Ackerman, Steven J.; Furuta, Glenn T.
Esophageal aspergillosis after bone marrow transplant
The prolonged immune suppression associated with bone marrow transplants predisposes to fungal infections including Aspergillus. Disseminated aspergillosis occurs in up to 60% of patients with invasive pulmonary aspergillosis; sites of involvement include the brain, gastrointestinal tract, kidney, liver, thyroid, heart, and spleen. There is only one report of isolated esophageal aspergillosis. A recent acute myelogenous leukemia patient had isolated esophageal
JH Choi; JH Yoo; IJ Chung; DW Kim; CW Han; WS Shin; WS Min; CC Kim; DJ Kim
CT appearance of implanted esophageal stents.
Three different types of esophageal stents, the Z-stent, Ultraflex, and Wall-stent, exhibit different shapes on CT, which may suggest a difference in the radial forces applied by each of the stents. CT is useful for displaying the relationship between an esophageal stent and adjacent structures and complications. PMID:10667652
Iwasaki, Y; Nakajima, Y; Ishikawa, T; Wakabayashi, M; Ashida, H
[Prenatal MRI diagnosis of esophageal atresia].
The diagnosis of esophageal atresia may be suspected on prenatal ultrasonography in fetuses with absent or small stomach, upper esophageal dilatation and unexplained polyhydramnios. However, the diagnostic value of these findings is relatively poor. Two cases are reported where MRI appeared to be accurate for establishing the diagnosis of this congenital anomaly. PMID:15692414
Chaumo�tre, K; Amous, Z; Bretelle, F; Merrot, T; D'Ercole, C; Panuel, M
High-resolution EUS in children with eosinophilic �allergic� esophagitis
Background: The pathophysiology of dysphagia associated with eosinophilic esophagitis is unknown. This study investigated possible anatomic alterations in children with eosinophilic esophagitis in comparison with healthy children by using high-resolution EUS to precisely measure individual tissue layers of the esophagus. Methods: Children with eosinophilic esophagitis (n = 11) and control children (n = 8) without esophagitis were prospectively evaluated by
Victor L. Fox; Samuel Nurko; Jonathan E. Teitelbaum; Kamran Badizadegan; Glenn T. Furuta
Expression of the neutral amino acids transporter ASCT1 in esophageal carcinomas.
Cancers cells utilize more glucose and amino acids than their benign counterparts. Overexpression of the facilitative glucose transporter Glut1 in human cancers was found to correlate with aggressive biologic behavior. The aim of this work was to determine whether the neutral amino acid transporter ASCT1 is expressed in human esophageal carcinomas, and to correlate the findings with Glut1 expression. Sections of formalin-fixed and paraffin-embedded tissue from 42 cases of esophageal carcinomas were entered in the study. Immunohistochemical staining was performed using a rabbit anti-ASCT1 IgG developed in our laboratory, and anti-Glut1 antibody, using standard avidin-streptavidine immunoperoxidase method. Sections of formalin-fixed and paraffin-embedded HepG2 cells were used as positive controls. The percent of ASCT1-positive cells was scored. Statistical analysis was performed using Fisher's exact test. ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous. Significantly more adenocarcinomas expressed ASCT1 than squamous cell carcinomas (p < 0.0001), whereas Glut1 expression was similar in both tumor types. There was no association between the expression of either transporter and lymph node metastasis. Glut1 was expressed more often in the better differentiated than the poorly differentiated squamous carcinomas (p = 0.003). These results suggest that unlike in squamous cell carcinoma, ASCT1 plays a significant role in the recruitment of amino acids in adenocarcinoma of the esophagus, and suggest that the metabolic needs, and uptake of nutrients, are regulated differently in these two tumor types. Additional studies with larger number of patients are needed to determine the biological significance of ASCT1 expression in esophageal carcinomas. PMID:11268453
Younes, M; Pathak, M; Finnie, D; Sifers, R N; Liu, Y; Schwartz, M R
Ingestion of thioproline suppresses rat esophageal adenocarcinogenesis caused by duodenogastroesophageal reflux.
Duodenogastroesophageal reflux causes esophageal adenocarcinoma in rats without the use of a carcinogen. This etiology is unclear, but may be associated with endogenous nitrosation in the gastrointestinal tract. Thioproline (TPRO) is an effective nitrite-trapping agent and blocks endogenous nitrosation. We investigated how ingested TPRO affected esophageal adenocarcinogenesis in rats with duodenogastroesophageal reflux (DGER) or gastroesophageal reflux (GER). A series of 200 male Fischer 344 rats received surgery to induce reflux of duodenogastric contents or gastric contents alone into the esophagus. The rats were separated into two divisions according to the surgical procedure employed (DGER or GER), and each division was further subdivided into two groups: one group was fed a special diet (CRF-1 containing 0.5% of TPRO); the other group was fed a standard diet (CRF-1). The rats were given no carcinogen and sacrificed at ten-week intervals from the 25th to the 45th week after surgery. Pathological examination was carried out using hematoxylin-eosin or immunohistochemical staining. Erosion, regenerative thickening, basal cell hyperplasia and columnar-lined epithelium (CLE) were found in both groups of the DGER rats. Adenocarcinoma (AC) appeared only in the DGER rats sacrificed at 35 and 45 weeks following surgery. The incidence of AC at the 45th week was significantly lower in the group of rats fed the diet containing TPRO, as compared to those fed the standard diet, whereas the incidences of CLE were the same for both groups. iNOS protein and nitrotyrosine protein were identified in the CLE and macrophages of the DGER group using immunohistochemical staining. There were no remarkable pathological changes in the esophagi of the rats which underwent the GER procedure. In conclustion, TPRO has an inhibitory effect on esophageal reflux-induced adenocarcinogenesis in rats in that it prevents the progression from CLE to AC. PMID:17982628
Sasaki, Shozo; Miwa, Koichi; Fujimura, Takashi; Oba, Masaru; Miyashita, Tomoharu; Kinami, Shinichi
Pancreatic adenocarcinoma in guinea fowl
Pancreatic adenocarcinoma is a rare neoplasm of poultry. This condition is hereby described in an adult male guinea fowl that died suddenly in a flock of apparently healthy birds. Necropsy showed severe ascites and nodular tissue growths on the serous membranes of some internal organs and in the parenchyma of the pancreas only. Histopathological sections of the organs had neoplastic
J. O. A. Okoye; C. C. Ilochi
Clubbing associated with oesophageal adenocarcinoma.
A patient with an oesophageal adenocarcinoma, recent onset of digital clubbing, and evidence of increased oestrogen synthesis is presented. In the discussion, some of the theories of the pathogenesis of clubbing are reviewed, together with previous reports of clubbing in gastro-oesophageal disorders. A possible unifying theory is proposed for our case which we believe is the first report of this triple association.
Polkey, M. I.; Cook, G. R.; Thomson, A. D.; Taylor, N. F.
Adenocarcinoma in the exstrophic bladder
We report 2 cases of cancerous transformation in an exstrophic bladder. The histology of these tumors, methods of surveillance, and treatment are discussed in conjunction with a review of published reports. These rare tumors are almost entirely adenocarcinomas. Their treatment is surgical (radical cystectomy) with or without associated radiation therapy. Surveillance for patients with bladder exstrophy, whether surgically corrected or
P Paulhac; F Maisonnette; S Bourg; J. P Dumas; P Colombeau
Ovarian Adenocarcinoma of Mesonephric Type.
National Technical Information Service (NTIS)
Ovarian adenocarcinoma of mesonephric type is a well-differentiated carcinoma composed of clear or hobnail-type cells resembling renal carcinoma. Forty cases were studied. Although there is no proof of origin from mesonephric remnants in or near the ovary...
H. J. Norris M. Robinowitz
Hepatic granulomata associated with adenocarcinoma
A case is described in which extensive investigations failed to reveal the cause of hepatic granulomata, except that at post-mortem an adenocarcinoma of the lung was found; an association between the two is therefore suggested. ImagesFig. 1Fig. 2
Rebello, R.; Warnes, T. W.
Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy.
From 1975 through 1988, 257 patients with carcinoma of the thoracic esophagus have been treated in our department. Operability was 90% (232/257); overall resectability, 77% (198/257), and for the operated group, 85% (198/232). Hospital mortality rate was 9.6% but decreased to 3% over the period 1986 to 1988. There were 65% squamous cell epitheliomas and 35% adenocarcinomas. Tumor, nodes, and metastases (pTNM) staging was as follows: stage I, 11.6%; stage II, 23.2%; stage III, 37.9%; stage IV, 27.3%. Overall survival rate was 62.5% at 1 year, 42.4% at 2 years, and 30% at 5 years. According to the pTNM staging, 5-year survival was 90% for stage I, 56% for stage II, 15.3% for stage III, and 0 for stage IV. There were no statistically significant differences according to tumor localization, pathologic type, sex, or age. Introducing extensive resection and extended lymphadenectomy seems to improve significantly survival in patients in whom an operation with curative intention was performed, the 1 year survival rate being 90.8% versus 72%; 2-year survival, 81% versus 46%; and 5-year survival, 48.5% versus 41% for radical and nonradical resections, respectively. Based on multivariate Cox regression analysis, only TNM stage and presence or absence of lymph nodes are important factors in predicting survival: stage 1 tumors have lower risk, and involvement of lymph nodes creates higher risk. Using this analysis, there was only for the patients with involved lymph nodes (N1) a significantly better prognosis when a radical lymph node dissection was performed (p = 0.0055). Barrett adenocarcinomas have no worse prognosis than other esophageal carcinomas, with a 5-year survival rate of 91.5% if lymph nodes are negative, and a 54% overall 5-year survival rate. Functional results after restoration of continuity with gastric tubulation were judged excellent to very good in 86.5% at 1 year, but infra-aortic anastomoses have a much higher incidence of peptic esophagitis: 53% versus 8% for cervical anastomoses. From this study it can be concluded that in experienced hands surgery today offers the best chances for optimal staging, potential cure, and prolonged high-quality palliation.
Lerut, T; De Leyn, P; Coosemans, W; Van Raemdonck, D; Scheys, I; LeSaffre, E
Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population.
Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome-wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk-related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case-control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio�=�0.90; 95% confidence interval, 0.81-0.99; P�=�0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double-edged sword, as modulator between the carcinogenesis processes of stomach and esophagus. PMID:24654646
Dai, Ningbin; Zheng, Mingfeng; Wang, Cheng; Ji, Yong; Du, Jiangbo; Zhu, Chen; He, Yisha; Zhu, Meng; Zhu, Xun; Sun, Min; Dai, Juncheng; Ma, Hongxia; Chen, Jingyu; Hu, Zhibin; Gu, Haiyong; Jin, Guangfu; Shen, Hongbing
Expression of COX2 and p53 in Rat Esophageal Cancer Induced by Reflux of Duodenal Contents
Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.
Hashimoto, Naoki
Adenocarcinoma of the Esophagogastric Junction
Objective To assess the outcome of surgical therapy based on a topographic/anatomical classification of adenocarcinoma of the esophagogastric junction. Summary Background Data Because of its borderline location between the stomach and esophagus, the choice of surgical strategy for patients with adenocarcinoma of the esophagogastric junction is controversial. Methods In a large single-center series of 1,002 consecutive patients with adenocarcinoma of the esophagogastric junction, the choice of surgical approach was based on the location of the tumor center or tumor mass. Treatment of choice was esophagectomy for type I tumors (adenocarcinoma of the distal esophagus) and extended gastrectomy for type II tumors (true carcinoma of the cardia) and type III tumors (subcardial gastric cancer infiltrating the distal esophagus). Demographic data, morphologic and histopathologic tumor characteristics, and long-term survival rates were compared among the three tumor types, focusing on the pattern of lymphatic spread, the outcome of surgery, and prognostic factors in patients with type II tumors. Results There were marked differences in sex distribution, associated intestinal metaplasia in the esophagus, tumor grading, tumor growth pattern, and stage distribution between the three tumor types. The postoperative death rate was higher after esophagectomy than extended total gastrectomy. On multivariate analysis, a complete tumor resection (R0 resection) and the lymph node status (pN0) were the dominating independent prognostic factors for the entire patient population and in the three tumor types, irrespective of the surgical approach. In patients with type II tumors, the pattern of lymphatic spread was primarily directed toward the paracardial, lesser curvature, and left gastric artery nodes; esophagectomy offered no survival benefit over extended gastrectomy in these patients. Conclusion The classification of adenocarcinomas of the esophagogastric junction into type I, II, and III tumors shows marked differences between the tumor types and provides a useful tool for selecting the surgical approach. For patients with type II tumors, esophagectomy offers no advantage over extended gastrectomy if a complete tumor resection can be achieved.
Rudiger Siewert, J.; Feith, Marcus; Werner, M.; Stein, Hubert J.
Radiographic demonstration of esophageal and tracheal fistulas at autopsy using a contrasting medium that vulcanizes at room temperature.
Esophageal and tracheal fistulas, which occur in 0.05% of medicolegal autopsies, were demonstrated in three cases by a postmortem radiographic technique using silicone rubber/lead oxide as a contrasting medium that vulcanizes at room temperature. In one 83-year-old male, a tracheoesophageal fistula was detected, which had developed after surgical repair of an esophageal rupture caused by a flexible fiberoptic endoscope. In a second case, carcinoma of the esophagus in a 78-year-old male had eroded the trachea and arcus of the aorta creating a fatal tracheoesophagoaortic fistula. In a third case, 55-year-old female developed a tracheobrachicephalic artery fistula as a result of an infiltrating cystic adenocarcinoma of the trachea, resulting in a fatal hemorrhage into the trachea. The results of this study indicate that diagnostic radiologic methods using a vulcanized contrasting medium are useful in supplementing normal dissection in autopsy cases with suspected fistulas of the esophagus or trachea. PMID:1919472
Karhunen, P J; Lalu, K
47 CFR 11.41 - Participation in EAS.
Code of Federal Regulations, 2011 CFR
...Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization � 11.41 Participation in EAS. (a) All EAS Participants specified in � 11.11...
47 CFR 11.41 - Participation in EAS.
Code of Federal Regulations, 2012 CFR
...Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization � 11.41 Participation in EAS. All EAS Participants specified in � 11.11 are...
47 CFR 11.61 - Tests of EAS procedures.
Code of Federal Regulations, 2011 CFR
...of EAS procedures. 11.61 Section 11.61 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Tests � 11.61 Tests of EAS procedures. (a) EAS Participants shall conduct tests at...
47 CFR 11.61 - Tests of EAS procedures.
Code of Federal Regulations, 2012 CFR
...of EAS procedures. 11.61 Section 11.61 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Tests � 11.61 Tests of EAS procedures. (a) EAS Participants shall conduct tests at...
47 CFR 11.61 - Tests of EAS procedures.
Code of Federal Regulations, 2010 CFR
...2010-10-01 2010-10-01 false Tests of EAS procedures. 11.61 Section 11.61 Telecommunication...COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Tests § 11.61 Tests of EAS procedures. (a) EAS Participants...
47 CFR 11.61 - Tests of EAS procedures.
Code of Federal Regulations, 2010 CFR
...2009-10-01 2009-10-01 false Tests of EAS procedures. 11.61 Section 11.61 Telecommunication...COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Tests § 11.61 Tests of EAS procedures. (a) EAS Participants...
47 CFR 11.61 - Tests of EAS procedures.
Code of Federal Regulations, 2013 CFR
...of EAS procedures. 11.61 Section 11.61 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Tests § 11.61 Tests of EAS procedures. (a) EAS Participants shall conduct tests at...
47 CFR 11.41 - Participation in EAS.
Code of Federal Regulations, 2013 CFR
...Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization § 11.41 Participation in EAS. All EAS Participants specified in § 11.11 are...
[Non-neoplastic esophageal stenosis: not always so benign].
Esophageal intramural pseudodiverticulosis is a rare pathology whose etiology is unknown, but which is frequently associated with three highly prevalent entities: esophageal reflux disease, esophageal candidosis and alcoholic esophagitis. With conservative treatment the course of these pathologies is usually benign. However, some severe cases are resistant to conservative treatment and may require more aggressive management. We here present the case of patient suffering from a severe esophagitis complicated by chronic mediastinitis with life-threatening repercussions, requiring esophagectomy as treatment. PMID:24088236
Lorenz, Julie; Vollenweider, Peter; Vuilleumier, Henri; Schwab, Marcos
Association of esophageal candidiasis and squamous cell carcinoma
Chronic esophageal candidiasis is an infection that is mostly seen in immunocompromised conditions, among which is chronic mucocutaneous candidiasis (CMC). Recently an association between CMC and esophageal carcinoma has been reported. Here we present two patients with chronic esophageal candidiasis who developed esophageal squamous cell carcinoma and we discuss the etiologic role of Candida-induced nitrosamine production, the loss of STAT1 function and impaired tumor surveillance and T-lymphocyte function in the development of esophageal carcinoma.
Delsing, C.E.; Bleeker-Rovers, C.P.; van de Veerdonk, F.L.; Tol, J.; van der Meer, J.W.M.; Kullberg, B.J.; Netea, M.G.
Survival Effect of Neoadjuvant Radiotherapy Before Esophagectomy for Patients With Esophageal Cancer: A Surveillance, Epidemiology, and End-Results Study
Purpose: The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. Methods and Materials: The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed with NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. {<=}10), histologic type (adenocarcinoma vs. squamous cell carcinoma), age (<65 vs. {>=}65 years), and gender as covariates. Results: A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. Conclusion: These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.
Schwer, Amanda L. [Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, Colorado (United States)], E-mail: email@example.com; Ballonoff, Ari; McCammon, Robert; Rusthoven, Kyle [Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, Colorado (United States); D'Agostino, Ralph B. [Department of Biostatistical Science, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Schefter, Tracey E. [Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, Colorado (United States)
Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas.
Upper gastrointestinal neoplasia in the esophagus, stomach, and pancreas is associated with the formation of preneoplastic metaplasias. We have previously reported the up-regulation of human epididymis protein 4 (HE4) in all metaplasias in the stomach of humans and mice. We have now sought to evaluate the expression of HE4 in metaplasias/preneoplastic precursors and cancers of the human stomach, pancreas, and esophagus. Tissue microarrays for gastric cancers, pancreatic cancers, and esophageal adenocarcinoma were stained with antibodies against HE4. Immunostaining was quantified by digital imaging, and the results were evaluated to assess the expression in metaplasias, the expression in cancer pathological subtypes, and the effects of expression on survival in patients with cancer. In patients with gastric cancer from Korea, HE4 was detected in 74% of intestinal and 90% of diffuse cancers, whereas in a gastric cancer cohort from Johns Hopkins, HE4 was detected in 74% of intestinal-type and 92% of diffuse cancers. Nevertheless, in both cohorts, there was no impact of HE4 expression on overall survival. In the esophagus, we observed the expression of HE4 in scattered endocrine cells within Barrett esophagus samples, but Barrett columnar metaplasias and HE4 were detected in only 2% of esophageal adenocarcinomas. Finally, in the pancreas, HE4 expression was not observed in pancreatic intraepithelial neoplasia lesions, but 46.8% of pancreatic adenocarcinomas expressed HE4. Still, we did not observe any influence of HE4 expression on survival. The results suggest that HE4 is up-regulated during gastric and pancreatic carcinogenesis. PMID:23084584
O'Neal, Ryan L; Nam, Ki Taek; LaFleur, Bonnie J; Barlow, Brittney; Nozaki, Koji; Lee, Hyuk-Joon; Kim, Woo Ho; Yang, Han-Kwang; Shi, Chanjuan; Maitra, Anirban; Montgomery, Elizabeth; Washington, M Kay; El Rifai, Wael; Drapkin, Ronny I; Goldenring, James R
Esophageal carcinoma: long-term survival in consecutive series of patients through a retrospective cohort study
Aim The present study aimed to investigate the influence of histological factors on survival of patients with esophageal cancer. Background Esophageal cancer is almost the common form of malignancy in the eastern world. Patients and methods Through a retrospective cohort study a consecutive series of 134 patients with definite diagnosis of esophageal cancer who had been hospitalized at the Towhid hospital, Sanandaj city, Kurdistan province western Iran during a five-year period from 2006 onward were recruited. The survival time of patients stratified by this grouping method were analyzed by Kaplan-Meier analysis and Cox regression. Results Overall, 127 males (55.1%), with a mean age of 65.38 �11.62 years were included. Based on histological type of tumor, 23 patients (18.1%) had adenocarcinoma (AC) and 94 patients (74.0%) had squamous cell carcinoma (SCC). Gender was not significantly associated with survival (Log rank =0.480). Location of tumor (log rank =0.014), histological type (log rank ?0.001) and grade of tumor (log rank =0.008) had significantly influenced the survival rates variation. For patients at initial stages of the disease, the overall one-year, two years and five years survival rates were 73.2%, 52.8% and 31.2% respectively. For advanced stages, the survival ranged from 46.3% in the first year to 8.2% in the five years. The five-year survival rates (by year) were estimated to be 49%, 27%, 24%, 22% and 19% respectively. Conclusion Tumor grade, tumor deferential, clinical staging and location of the tumor were the prognostic factors for survival in patients with esophageal cancer.
Delpisheh, Ali; Sayehmiri, Kourosh; Rahimi, Ezzatollah
Thoracoscopic repair of esophageal atresia and tracheoesophageal fistula in neonates, first decade's experience.
The first thoracoscopic esophageal atresia with tracheoesophageal fistula (EATEF) repair was performed in March of 2000. This report evaluates the results and evolution of the technique in a single surgeons' experience after the first decade of thoracoscopic EATEF repair. From March 2000 to September 2012, 52 consecutive patients with type 3 EATEF, and an additional nine patients with pure esophageal atresia (EA) were repaired by or under the direct supervision of a single surgeon. Patient weight ranged from 1.2 to 3.8?kg (mean 2.6?kg). Twenty-two patients had significant associated congenital anomalies. The repairs were performed using three ports. The fistula was ligated using a single endoscopic clip, and the anastomosis was performed using a single layer of interrupted sutures. A transanastomotic tube and chest drain were left in all cases. Fifty-one of the 52 procedures were completed successfully thoracoscopically. Operative times ranged from 50 to 120 minutes (average 85 minutes). There were three clinical leaks, one in an EATEF and two in patients with long-gap pure EA, all resolved with conservative therapy. Oral feedings were started on day 5 in all other patients. Twelve of 61 patients required dilations (1-9), and 18 required a Nissen fundoplication for severe reflux. One patient required a thoracoscopic aortopexy for severe tracheomalacia. All patients are currently on full oral feedings. No patient has any evidence of chest wall asymmetry, winged scapula, or clinically significant scoliosis. There have been no recurrent fistulas. Thoracoscopic EA repair has proven to be an effective and safe technique. Initial experience resulted in a higher stricture rate, but this improved with experience and changes in technique. The results are superior to that of documented open series and avoid the morbidity of an open thoracotomy. PMID:23679024
Rothenberg, S S
[Oral blastomycosis, laryngeal papillomatosis and esophageal tuberculosis].
Esophageal involvement is an extremely rare complication of tuberculosis even in countries with high prevalence of infection. We report the case of a 57 year-old hiv-seronegative patient with simultaneous diagnoses of oral blastomycosis and laryngeal papillomatosis. Both were confirmed by anatomopathological analysis. The esophageal biopsy revealed granulomatous esophagitis with necrosis and ziehl-neelsen stain showed acid-fast alcohol resistant bacilli suggestive of tuberculosis. The patient's history included pulmonary tuberculosis twice and previous abandonment of therapy. Thus, it was necessary to use oral itraconazole combined with second-line anti-tuberculosis drugs administered through a gastrostomy tube. The clinical development was favorable. PMID:22858774
Montoya, Manuel; Chumbiraico, Robert; Ricalde, Melvin; Cazorla, Ernesto; Hern�ndez-C�rdova, Gustavo
Esophageal melanocytosis in oral opium consumption.
Esophageal melanocytosis is a rare and benign condition, characterized by melanocytic proliferation of the esophageal squamous epithelium with heavy melanin deposition. The etiology and pathogenesis has not been exactly known but it seems to be a chronic stimulus such as gastroesophageal reflux. This condition is very rare and about 35 cases have been reported so far, most of which have been from India and Japan. Herein, we present a case of esophageal melanocytosis in a patient with long history of oral opium consumption. To the best of our knowledge, such a history has not been reported. PMID:24719715
Geramizadeh, Bita; Asadian, Fatemeh; Taghavi, Alireza
Esophageal Melanocytosis in Oral Opium Consumption
Esophageal melanocytosis is a rare and benign condition, characterized by melanocytic proliferation of the esophageal squamous epithelium with heavy melanin deposition. The etiology and pathogenesis has not been exactly known but it seems to be a chronic stimulus such as gastroesophageal reflux. This condition is very rare and about 35 cases have been reported so far, most of which have been from India and Japan. Herein, we present a case of esophageal melanocytosis in a patient with long history of oral opium consumption. To the best of our knowledge, such a history has not been reported.
Geramizadeh, Bita; Asadian, Fatemeh; Taghavi, Alireza
Correlation of esophageal manometry and radionuclide esophageal transit in normal subjects.
What was the correlation of esophageal manometry and scintigraphy in Chinese was studied. Thirty-two volunteers (M/F: 18/14, age: 20-57) without evident esophageal motor disturbance and chest deformity underwent manometric measurement in the spine position using a low compliance pneumohydraulic infusion system. These measurements included the location of both upper and lower esophageal sphincter from nostril, and dry or wet swallow elicited peristaltic speed in the lower esophageal segment. Within one week after manometry, they swallowed a technetium-99m colloid bolus to measure radionuclide manifested esophageal transit time in the supine position beneath a gamma-camera. Body heights of enrolled subjects exhibited a significant positive correlation (r = 0.458, p < 0.01) with manometry measured esophageal lengths. Mean radionuclide esophageal transit time was 7.61 +/- 2.51 sec (3.1-13.57 sec). These transit times exhibited a positive correlation with esophageal lengths (r = 0.6, p < 0.001). Radionuclide transit speed was actually slower than either dry swallow or wet swallow elicited speed (p < 0.05). In conclusion, either manometry or scintigraphy manifests their specific benefits to diagnose esophageal motility disorders. Some correlations of measured variables can be obtained if they are simultaneously employed. PMID:8549235
Chang, F Y; Lee, C T; Yeh, C L; Lee, S D; Chu, L S
Statins Are Associated with Reduced Risk of Esophageal Cancer, Particularly in Patients with Barrett's Esophagus: A Systematic Review and Meta-Analysis
Background & Aims Esophageal cancer is increasing in incidence in US, especially among patients with Barrett�s esophagus (BE). Statins might prevent this cancer. We performed a systematic review with meta-analysis of studies that evaluated the effect of statins on the risk of esophageal cancer. Methods We conducted a systematic search of Medline, Embase, and Web of Science through August 2012. Studies were included if they evaluated exposure to statins, reported the development of esophageal cancer, and reported relative risks or odds ratios (ORs), or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model. The analysis included 13 studies (including a post-hoc analysis of 22 randomized controlled trials) reporting 9285 cases of esophageal cancer among 1,132,969 patients. Results Meta-analysis of the studies showed a significant (28%) reduction in incidence of esophageal cancer among patients who took statins (adjusted OR, 0.72; 95% CI, 0.60�0.86), though there was considerable heterogeneity among studies. In analyzing a subset of patients known to have BE (5 studies, 312 esophageal adenocarcinomas [EAC] developed in 2125 patients), statins were associated with a significant (41%) decrease in the risk of EAC, after adjusting for potential confounders (adjusted OR, 0.59; 95% CI, 0.45�0.78) with consistent results among all studies. The number needed to treat with statins to prevent 1 case of EAC in patients with BE was 389. Conclusions Meta-analysis of existing observational studies indicates that statins protect against esophageal cancer and reduce the risk of EAC in patients with BE.
Singh, Siddharth; Singh, Abha Goyal; Singh, Preet Paul; Murad, Mohammad Hassan; Iyer, Prasad G.
Poorly Differentiated Colorectal Adenocarcinoma (Methodology)
Poorly differentiated adenocarcinoma (PDAC) constitutes ? 2�25% of all colorec-tal carcinomas (CRCs) (Riddle et al., 2003; Ueno et al., 2002). In Japan, the frequency of PDAC among CRCs has been reported to be>5%, whereas it is between 10�25% in Western countries\\u000a (Taniyama et al., 1991). Clinically, PDAC often penetrates deep through the bowel wall and frequ ently metastasizes to the
Seiichi Shinji; Zenya Naito; Toshiyuki Ishiwata; Matsuda Yoko; Tomoko Seya; Takashi Tajiri
NASA Astrophysics Data System (ADS)
The muon-hadron detector of EAS-TOP is a 270 sq m calorimeter constructed inside the air shower array on the top of the underground Gran Sasso Laboratory (Italy). The general layout of the detector and the performances of the active part (streamer and proportional chambers) are presented.
Aglietta, M.; Alessandro, B.; Arneodo, F.; Bergamasco, L.; Campos Fauth, A.; Castagnoli, C.; Castellina, A.; Cattadori, C.; Chiavassa, A.; Cini, G.
Esophageal ulceration induced by intracavitary irradiation for esophageal carcinoma
Twenty-two patients with esophageal carcinoma had no local recurrence after external and intracavitary radiation treatment, but all developed ulcers in the field of intracavitary irradiation. Ten were linear ulcers that appeared 3-12 months after radiation treatment (mean, 5.3 months); the other 12 were the long circumferential type and appeared 1-8 months after irradiation (mean, 3.7 months). Esophagobronchial fistulae developed in two cases in which deep ulcer had been found between the completion of external irradiation and the beginning of intracavitary irradiation. In these cases with deep ulcer, intracavitary irradiation should not be done. For patients receiving intracavitary radiation, the total dosage should be less than 20 Gy.
Hishikawa, Y.; Tanaka, S.; Miura, T.
Roentgenologic Diagnosis of Sliding Esophageal Hiatus Hernia.
National Technical Information Service (NTIS)
On the basis of the study of 210 cases of sliding esophageal hiatus hernia (SEHH) and normal esophagogastric regions in 40 subjects, 4 roentgenologic diagnostic features have been suggested: supraphrenic hernial sac, the gastric mucosa appears supradiaphr...
C. Xingrong
Nucleolar organiser regions in adenocarcinoma in situ and invasive adenocarcinoma of the cervix
Silver binding nucleolar regions (AgNORs) were evaluated in normal endocervix, adenocarcinoma, and its potential precursor, adenocarcinoma in situ (AIS), in an attempt to increase an understanding of the natural history of cervical adenocarcinoma and to identify a marker for abnormal endocervical (atypical glandular) cells which could aid diagnosis and follow up of endocervical lesions. For every 50 cells the mean
J F Darne; S V Polacarz; E Sheridan; D Anderson; R Ginsberg; F Sharp
Exclusively Endoscopic Resection of Nasopharyngeal Adenocarcinoma
We reported two patients with nasopharyngeal adenocarcinoma resected by using the exclusively endoscopic approach. Case reports and a review of the world literature concerning nasopharyngeal adenocarcinoma. The tumors were resected successfully via the exclusively endoscopic approach and no conversions to the conventional approach were necessary. The two patients were followed up for 26 and 18 months respectively, and no recurrence was noted without postoperative chemotherapy or radiotherapy. To the best of our knowledge, this is the first report of endoscopic resection of nasopharyngeal adenocarcinoma. Our experience revealed that not only for the early recurrent nasopharyngeal carcinoma, the exclusively endoscopic nasopharyngectomy can be expanded for the resection of selected nasopharyngeal adenocarcinoma.
Lai, Yu-Shih
The ultraflex stents for malignant esophageal obstruction.
Ultraflex esophageal stents have contributed to the tremendous success of self-expanding metal stents (SEMS) in the treatment of esophageal cancer because they are easy and safe to insert. With an eye to improving clinical outcome, the Ultraflex stent design has been in a state of constant evolution since its introduction. However, as with other SEMS, a high reintervention rate remains a challenging problem. PMID:10388856
Mokhashi, M S; Hawes, R H
Extrapleural suction buttress of primary esophageal repair.
Buttress reinforcement of a primary esophageal repair after perforation may diminish the potential for breakdown or leakage of the approximation. We describe a method of reinforcing a primary esophageal repair by using pleural tissue that is secured in place with an extrapleural, soft T-tube attached to a suction device. This technique is simple to apply and may maximize recovery of respiratory function by permitting timely removal of chest tubes.
Takach, T J; Gregoric, I; Campbell, J D
Proton Pump Inhibitor Impact on Esophageal Eosinophilia
Objective Differentiation between the common etiologies of dense esophageal eosinophilia such as gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE), can be difficult. We hypothesized that histologic features may provide diagnostic clues concerning the etiology of esophageal eosinophilia. Methods We performed a retrospective chart review of 204 children with the diagnosis of esophagitis characterized by ? 15 eos/ HPF in at least one biopsy. We then restricted our analysis to subjects who had received at least 8 weeks of only proton pump inhibitors (PPIs) followed by endoscopy and who had a clinicopathologic response to this treatment. Symptoms, endoscopic findings, and pathologic descriptions were reviewed and an eosinophil peroxidase (EPX) index was determined to assess for degranulation/eosinophil activation. Results Of the 204 identified charts, 7 subjects identified met the inclusion criteria. Five of these 7 patients showed a clinicopathologic response to PPIs after their follow up endoscopy, (mean peak eosinophil count- 92 vs 5 eos/ HPF, and EPX index-39.2 vs 14.6, pre- and post-treatment respectively). Two patients experienced initial resolution of symptoms and esophageal eosinophilia with PPI therapy however; within 17�23 months redeveloped symptoms and esophageal eosinophilia while on PPI therapy at the time of a third endoscopy (mean peak eosinophil count- 40 vs 11 vs 36 eos / HPF, and EPX index- 44 vs 21 vs 36.5, pre-, post- and post-treatment respectively). No clinicopathologic features or degranulation patterns differentiated subjects with GERD / PPI responsive esophageal eosinophilia (PPIREE) from those who had transient response to PPI treatment. Conclusions No clinicopathologic features differentiated subjects who responded to PPI treatment. PPI treatment can be helpful to exclude GERD and PPIREE but long-term follow up is critical in the management of esophagitis.
Schroeder, Shauna; Capocelli, Kelley E; Masterson, Joanne C; Harris, Rachel; Protheroe, Cheryl; Lee, James J; Furuta, Glenn T
Establishing Magnetic Resonance Imaging as an Accurate and Reliable Tool to Diagnose and Monitor Esophageal Cancer in a Rat Model
Objective To assess the reliability of magnetic resonance imaging (MRI) for detection of esophageal cancer in the Levrat model of end-to-side esophagojejunostomy. Background The Levrat model has proven utility in terms of its ability to replicate Barrett�s carcinogenesis by inducing gastroduodenoesophageal reflux (GDER). Due to lack of data on the utility of non-invasive methods for detection of esophageal cancer, treatment efficacy studies have been limited, as adenocarcinoma histology has only been validated post-mortem. It would therefore be of great value if the validity and reliability of MRI could be established in this setting. Methods Chronic GDER reflux was induced in 19 male Sprague-Dawley rats using the modified Levrat model. At 40 weeks post-surgery, all animals underwent endoscopy, MRI scanning, and post-mortem histological analysis of the esophagus and anastomosis. With post-mortem histology serving as the gold standard, assessment of presence of esophageal cancer was made by five esophageal specialists and five radiologists on endoscopy and MRI, respectively. Results The accuracy of MRI and endoscopic analysis to correctly identify cancer vs. no cancer was 85.3% and 50.5%, respectively. ROC curves demonstrated that MRI rating had an AUC of 0.966 (p<0.001) and endoscopy rating had an AUC of 0.534 (p?=?0.804). The sensitivity and specificity of MRI for identifying cancer vs. no-cancer was 89.1% and 80% respectively, as compared to 45.5% and 57.5% for endoscopy. False positive rates of MRI and endoscopy were 20% and 42.5%, respectively. Conclusions MRI is a more reliable diagnostic method than endoscopy in the Levrat model. The non-invasiveness of the tool and its potential to volumetrically quantify the size and number of tumors likely makes it even more useful in evaluating novel agents and their efficacy in treatment studies of esophageal cancer.
Kosovec, Juliann E.; Zaidi, Ali H.; Komatsu, Yoshihiro; Kasi, Pashtoon M.; Cothron, Kyle; Thompson, Diane V.; Lynch, Edward; Jobe, Blair A.
Lysyl oxidase-like 2 expression is increased in colon and esophageal tumors and associated with less differentiated colon tumors.
Lysyl oxidase-like 2 (LOXL2) belongs to an amine oxidase family whose members have been implicated in crosslink formation in stromal collagens and elastin, cell motility, and tumor development and progression. We previously demonstrated the association between increased LOXL2 expression and invasive/metastatic behavior in human breast cancer cells and mouse squamous and spindle cell carcinomas, interaction between LOXL2 and SNAIL in epithelial-mesenchymal transition, and localization of the LOXL2 gene to 8p21.2-21.3, within a minimally deleted region in several cancers, including colon and esophagus. In the present study, we analyzed LOXL2 expression in colon and esophageal tumors, and explored methylation as a regulator of LOXL2 expression. Immunohistochemistry using normal tissues demonstrated intracellular localization of LOXL2 in colonic enteroendocrine cells and esophageal squamous cells at the luminal surface, but not in mitotically active cells. Tissue array analysis of 52 colon adenocarcinomas and 50 esophageal squamous cell carcinomas revealed presence of LOXL2 expression in 83 and 92% of the samples, respectively, and a significant association between increased number of LOXL2-expressing cells and less-differentiated colon carcinomas. We determined that the methylation status of the 1150 bp 5' CpG island may contribute to the regulation of the gene. Loss of heterozygosity studies, using a microsatellite within intron 4 of the LOXL2 gene, revealed that loss of LOXL2 was unlikely to play a major role in either colon or esophageal tumors. These results suggest that increased LOXL2 expression in colon and esophageal cancer may contribute to tumor progression. PMID:17394133
Fong, Sheri F T; Dietzsch, Erin; Fong, Keith S K; Hollosi, Peter; Asuncion, Lloyd; He, Qingping; Parker, M Iqbal; Csiszar, Katalin
Laryngopharyngeal reflux in patients with reflux esophagitis
AIM: To assess the prevalence of laryngopharyngeal reflux (LPR) in patients with reflux esophagitis and disclose factors contributing to the development of LPR. METHODS: A total of 167 patients who proved to have reflux esophagitis by endoscopy were enrolled. They received laryngoscopy to grade the reflux findings for the diagnosis of LPR. We used validated questionnaires to identify the presence of laryngopharyngeal symptoms, and stringent criteria of inclusion to increase the specificity of laryngoscopic findings. The data of patients were analyzed statistically to find out factors related to LPR. RESULTS: The prevalence rate of LPR in studied subjects with reflux esophagitis was 23.9%. Age, hoarseness and hiatus hernia were factors significantly associated with LPR. In 23 patients with a hiatus hernia, the group with LPR was found to have a lower trend of esophagitis grading. CONCLUSION: Laryngopharyngeal reflux is present in patients with reflux esophagitis, and three predicting factors were identified. However, the development of LPR might be different from that of reflux esophagitis. The importance of hiatus hernia deserves further study.
Lai, Yung-Chih; Wang, Pa-Chun; Lin, Jun-Chen
[Clinicopathological study of acute esophageal mucosal lesion].
Acute esophageal mucosal lesion (AEML) is a comprehensive disease that includes necrotizing esophagitis and acute erosive esophagitis, which result in upper gastrointestinal bleeding. However, little is known about AEML. We examined the clinicopathological features of 57 AEML cases. AEML presented as acute diffuse esophagitis showing an endoscopically erosive mucosa. The disease did not include corrosive injury, radiation-induced damage, infectious esophagitis, or acute exacerbation of chronic gastroesophageal reflux disease. AEML predominantly affected elderly men, and upper gastrointestinal bleeding was the frequent presenting symptom. Severe underlying diseases such as cranial nerve disease or pneumonia were observed in 98% of the patients. Esophageal sliding hernia and gastroduodenal ulcers were endoscopically observed in 67% and 63% of the patients, respectively. Deaths due to exacerbation of the underlying diseases accounted for 16%. Most cases rapidly improved with conservative management using a proton pump inhibitor or an H2 blocker. Therefore, AEML should be considered a disease having characteristics different from those of common gastroesophageal reflux disease. PMID:23831655
Kawauchi, Hirohito; Ohta, Tomoyuki; Matsubara, Yu; Yoshizaki, Koji; Sakamoto, Jun; Amitsuka, Hisato; Kimura, Keisuke; Maemoto, Atsuo; Orii, Fumika; Ashida, Toshifumi
Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma.
The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus. PMID:21820152
Brankley, Shannon M; Fritcher, Emily G Barr; Smyrk, Thomas C; Keeney, Matthew E; Campion, Michael B; Voss, Jesse S; Clayton, Amy C; Wang, Kenneth K; Lutzke, Lori S; Kipp, Benjamin R; Halling, Kevin C
Imaging of atmospheric EAS Cherenkov light at EAS-TOP
NASA Astrophysics Data System (ADS)
The atmospheric EAS Cherenkov light is imaged by means of a multianode photomultiplier, and the data are analyzed to study the events. The 64-pixel multianode photomultiplier has a photocathode measuring (2x2) sq cm and supports a quantum efficiency of 12 percent at 400 nm. The EAS Cherenkov light images are corrected for channel-gain differences and ADC pedestals, and the collected number of photons ranges from 1000-10,000/sq m corresponding to primary energies of approximately (10 exp 13/10 exp 14) eV. The distributions and the maximum/minimum elongation are shown to agree with calculations as well as previous experimental data. The multianode photomultiplier is shown to be an effective instrument for capturing images of atmospheric Cherenkov light.
Aglietta, M.; Alessandro, B.; Arneodo, F.; Bergamasco, L.; Campos Fauth, A.; Castagnoli, C.; Castellina, A.; Cattadori, C.; Chivassa, A.; Cini, G.
Effects of transdermal nicotine on lower esophageal sphincter and esophageal motility
Cigarette smoking has been shown to decrease lower esophageal sphincter pressure (LESP) by 19�42%. This decrease in LESP may be due to nicotine in the cigarette smoke or substances other than nicotine. The aim of this study was to evaluate the effects of a nicotine patch on esophageal motility since nicotine patches are devoid of all toxins present in the
Shailesh C. Kadakia; Henry Renom De la Baume; Richard T. Shaffer
IgG4-Related Esophageal Disease Presenting as Esophagitis Dissecans Superficialis With Chronic Strictures
IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform fibrosis and can be associated with tumefactive lesions. IgG4-related disease involving the upper gastrointestinal tract is rare and only two previous case reports have reported IgG4-related esophageal disease. We report the case of a 63-year-old female patient with a long-standing history of severe dysphagia and odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed endoscopic images consistent with esophagitis dissecans superficialis (sloughing esophagitis). An underlying autoimmune process was suspected and immunosuppressant agents were tried to control her disease. The patient eventually developed disabling dysphagia secondary to multiple chronic esophageal strictures. A diagnosis of IgG4-related disease was eventually made after reviewing esophageal biopsies and performing an immunohistochemical study with an anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. Our case report describes this unique case of IgG4-related esophageal disease presenting as chronic esophagitis dissecans with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease.
Dumas-Campagna, Myriam; Bouchard, Simon; Soucy, Genevieve; Bouin, Mickael
[Changes in mechanical and functional processes of the lower esophageal sphincter in patients with reflux esophagitis].
The present study was performed to establish eventual inferences of functional and mechanical alterations of the lower esophageal sphincter (LES) in determining reflux esophagitis. The LES basal pressure, the percentual incidence of the incoordinate LES relaxations swallowing-induced, the LES overall and abdominal length, with gastroesophageal reflux disease (GERD), with and without endoscopic evidence of esophagitis, were manometrically evaluated in 117 consecutive patients. In patients with symptomatic GERD, a significant LES pressure reduction, which is inversely related to the severity of the endoscopic mucosal damage, an increased prevalence of the incoordinate LES relaxations swallowing-induced and, only in patients with esophagitis, a significant reduction of the LES overall and abdominal length of the LES, were showed. Two or three alterations of the LES antireflux devices can occur in the same patient, thus increasing the risk of esophagitis. PMID:2251450
Pustorino, S; Migliorato, D; Ianni, G; Martinez, P; Guerrisi, O; Federico, G; Luzza, G
Neurological manifestation of colonic adenocarcinoma
Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.
Sio, Terence T.; Paredes, Mercedes; Uzair, Chaudhary
Improved Esophageal Fistula Closure Devices for Cattle and Sheep.
National Technical Information Service (NTIS)
This publication describes a redesigned esophageal fistula plug and an esophageal cannula. These closure devices set forth state-of-the-art structural design, are more rugged, require minimal time to construct, and are relatively light when compared with ...
D. M. Anderson D. L. Mertz W. E. Franklin P. J. Manz
Smoking, Drinking Combo Raises Odds for Esophageal Cancer
Evaluation of Esophageal Motor Function With High-resolution Manometry.
For several decades esophageal manometry has been the test of choice to evaluate disorders of esophageal motor function. The recent introduction of high-resolution manometry for the study of esophageal motor function simplified performance of esophageal manometry, and revealed previously unidentified patterns of normal and abnormal esophageal motor function. Presentation of pressure data as color contour plots or esophageal pressure topography led to the development of new tools for analyzing and classifying esophageal motor patterns. The current standard and still developing approach to do this is the Chicago classification. While this methodical approach is improving our diagnosis of esophageal motor disorders, it currently does not address all motor abnormalities. We will explore the Chicago classification and disorders that it does not address. PMID:23875094
Conklin, Jeffrey L
?-fetoprotein produced by endometrioid adenocarcinoma of uterus
?-fetoprotein (AFP) producing adenocarcinoma of endometrium is a rare tumour. It is mostly high grade and has poor prognosis. Lung metastases are common. In this article, the authors present a case of a 57-year-old woman with AFP producing adenocarcinoma of endometrium and history of bilateral metachronous breast cancer, with lung, subcutaneous and brain metastases.
Akhavan, Ali; Karimi Zarchi, Mojgan; Akhavan Tafti, Mahmood; Navabii, Hossein
MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit
We sought to investigate the demographics and tumor-associated features in patients with gastroesophageal (GE) malignancies referred to our Phase I Program who had formalin-fixed, paraffin-embedded tissue from archival or new biopsies tested for MET mutation and/or amplification. MET amplification was found in 5 of 76 (6.6%) patients (3/34 [8.8%] esophageal, 2/26 [7.7%] gastric and none in 22 gastroesophageal junction cancers). The only MET mutation detected in 3 of 41 (7.3%) patients was N375S. No demographic and histologic characteristics were associated with specific MET abnormalities. Median overall survival was 3 and 5 months for patients with and without a MET alteration, respectively (hazard ratio [HR] = 2.1; 95% CI, 0.8 to 5.5; P=.14). Sixteen of 81 (20%) patients were enrolled in a c-MET inhibitor trial. Best responses were stable disease in 3 patients (19%), including a patient with esophageal adenocarcinoma that remained on the trial for 9.9 months (wild-type for MET abnormality). All tumors with MET abnormality (n=3) progressed on a c-MET inhibitor in fewer than 2 months. In conclusion, MET abnormalities can be found in a small group of patients with GE adenocarcinoma and further studies are necessary to better characterize the prognostic and predictive impact of MET alterations.
Jardim, Denis L. Fontes; Gagliato, Debora de Melo; Falchook, Gerald S.; Janku, Filip; Zinner, Ralph; Wheler, Jennifer J.; Subbiah, Vivek; Piha-Paul, Sarina A.; Fu, Siqing; Murphy, Mariela Blum; Ajani, Jaffer; Tang, Chad; Hess, Kenneth; Hamilton, Stanley R.; Roy-Chowdhuri, Sinchita; Kurzrock, Razelle; Meric-Bernstam, Funda; Hong, David S.
Chemoprevention of esophageal squamous cell carcinoma
Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.
Stoner, Gary D. [Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210 (United States)], E-mail: firstname.lastname@example.com; Wang Lishu; Chen Tong [Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210 (United States)
[Treatment of esophageal anastomotic leak with self-expanding metal stent].
Esophageal anastomotic leak after resection surgery is very hard to treat and Has a high mortality rate. Surgical treatment is extremely difficult, burdened by complications of subsequent postoperative complications (inability to repair). The authors present a case of a patient who underwent a resection of upper stomach and lower esophagus due to adenocarcinoma of the esophagus- stomach junction (Siewert II). A digestive tract X-ray with water-soluble kontrast was performer after seven days- it show and anastomotic leak. However, the patient was hemodynamically stable. It enabled to implant a self-expanding metal stent (Ultraflex) to the place of leak. In this case the procedure was successful, and radiological examination on the 14th day confirmed closure of the leak. Implantation of a self-expanding metal prosthesis as a way to treat anastomotic leak is a therapeutic option worth recommendation. PMID:24483033
G?uszek, Stanis?aw; Kot, Marta; Nawacki, ?ukasz
Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer
Background Esophageal cancer (EC) is a frequently occurring cancer with poor prognosis despite combined therapeutic strategies. Many biomarkers have been proposed as predictors of adverse events. We sought to assess the prognostic value of biomarkers in predicting the overall survival of esophageal cancer and to help guide personalized cancer treatment to give patients the best chance at remission. Methods We conducted a systematic review and meta-analysis of the published literature to summarize evidence for the discriminatory ability of prognostic biomarkers for esophageal cancer. Relevant literature was identified using the PubMed database on April 11, 2012, and conformed to the REMARK criteria. The primary endpoint was overall survival and data were synthesized with hazard ratios (HRs). Results We included 109 studies, exploring 13 different biomarkers, which were subjected to quantitative meta-analysis. Promising markers that emerged for the prediction of overall survival in esophageal squamous cell cancer included VEGF (18 eligible studies, n?=?1476, HR?=?1.85, 95% CI, 1.55-2.21), cyclin D1 (12 eligible studies, n?=?1476, HR?=?1.82, 95% CI, 1.50-2.20), Ki-67 (3 eligible studies, n?=?308, HR?=?1.11, 95% CI, 0.70-1.78) and squamous cell carcinoma antigen (5 eligible studies, n?=?700, HR?=?1.28, 95% CI, 0.97-1.69); prognostic markers for esophageal adenocarcinoma included COX-2 (2 eligible studies, n?=?235, HR?=?3.06, 95% CI, 2.01-4.65) and HER-2 (3 eligible studies, n?=?291, HR?=?2.15, 95% CI, 1.39-3.33); prognostic markers for uncategorized ECs included p21 (9 eligible studies, n?=?858, HR?=?1.27, 95% CI, 0.75-2.16), p53 (31 eligible studies, n?=?2851, HR?=?1.34, 95% CI, 1.21-1.48), CRP (8 eligible studies, n?=?1382, HR?=?2.65, 95% CI, 1.64-4.27) and hemoglobin (5 eligible studies, n?=?544, HR?=?0.91, 95% CI, 0.83-1.00). Conclusions Although some modest bias cannot be excluded, this review supports the involvement of biomarkers to be associated with EC overall survival.
[Primary herpetic esophageal infection in an immunocompetent patient].
Herpetic esophageal primary infection is not a common event in immunocompetent patients. The case of a 27-year-old immunocompetent woman who developed herpetic esophagitis involving the whole esophagus as a manifestation of primary herpetic infection is presented. The endoscopic appearance initially suggested esophageal candidiasis, which is not an exceptional event. PMID:9044750
Montalvo, I I; Yuste, R; Rodr�guez, F; Gil, I; Castiella, A; Alzate, L F; Arenas, J I
Oropharyngeal and esophageal interrelationships in patients with nonobstructive dysphagia.
Normal swallowing requires the close functional coordination of the mouth, pharynx, and esophagus, and if one of these components becomes functionally impaired, it is likely that the others may be affected. Using videofluoroscopy and manometry in this study, we examined the esophageal phase of swallowing in 12 patients with oropharyngeal dysphagia (group A) and the oropharyngeal components of swallowing in 29 patients with esophageal motor dysfunction and nonobstructive dysphagia (group B). A wide range of esophageal function abnormalities was seen in the first group, including delayed esophageal body peristalsis, spontaneous or simultaneous (tertiary) contractions, esophageal body dilation, proximal bolus redirection, and poor lower esophageal sphincter relaxation. Manometrically, 92% of group A patients were classified as having nonspecific esophageal motility disorder (NSEMD). In a similar fashion, group B patients exhibited many oropharyngeal function abnormalities on videofluorography including disturbed lingual peristalsis, slowed pharyngeal transit time with poor constriction of pharyngeal muscles, and laryngeal vestibular and tracheal bolus penetration. Manometrically, group B patients were classified as having NSEMD, achalasia, diffuse esophageal spasm, nutcracker esophagus, scleroderma, and chronic intestinal pseudoobstruction. In conclusion, oropharyngeal function is significantly altered in patients with esophageal motility disorders and dysphagia, and esophageal motor dysfunction occurs in patients with oropharyngeal dysphagia. These changes may represent either a compensatory mechanism or concomitant involvement of the oropharynx or the esophagus by the underlying neuromotor disorder. We suggest that assessment by esophageal motility and videofluoroscopy of both the oropharyngeal and esophageal phases of swallowing may improve diagnosis and therapy in patients with nonobstructive dysphagia. PMID:1551345
Triadafilopoulos, G; Hallstone, A; Nelson-Abbott, H; Bedinger, K
Caustic esophageal strictures in children: 30 years� experience
Many children in developing countries continue to sustain caustic esophageal injures. The first line of treatment is dilatation, unless contraindicated, where 60% to 80% success rate is expected. In cases of failure, esophageal replacement is the only hope for achieving normal swallowing. Over the last 30 years, more than 850 cases of esophageal replacement were done in the Pediatric Surgery
Alaa F Hamza; Sameh Abdelhay; Hatem Sherif; Tarek Hasan; Hisham Soliman; Ashraf Kabesh; Ibraheem Bassiouny; Ahmed F Bahnassy
Multicomponent EAS observations from EAS-TOP and LVD at Gran Sasso.
NASA Astrophysics Data System (ADS)
EAS-TOP (at the surface) and LVD (deep underground) provide a telescope for a multicomponent study of Extensive Air Showers (EAS). Examples of different classes of events observed in coincidence and their physical significance are presented and discussed.
EAS-Top Collaboration; LVD Collaboration
EAS hadronic component caught by neutron monitors
NASA Astrophysics Data System (ADS)
Extended Air Showers (EAS) are created in the atmosphere by cosmic ray particles of super high energy (1014 eV and higher). An EAS consists of huge amount of particles of different kinds (electrons, photons, muons, hadrons). Till now a hadronic component of EAS remains little investigated. We studied the hadron component of EAS with the help of installation uniting the detector EAS "Carpet" and the standard neutron monitor (NM). The installation is at Baksan Neutrino Observatory, North Caucasus, N43.28, E42.69; 1700 m a.s.l. The EAS array "Carpet" has the effective area 200 m2 and registers basically the electron-photonic component of EAS. The neutron monitor 6-NM-64 has the effective area 6 m2 and a lower energy detecting threshold for nucleons 50 MeV. Our new data acquisition system for the neutron monitor allows us to register not only separate pulses, but also intervals between them with accuracy as high as 1 microsecond. With this system we studied for the first time the spatial-temporary distribution of hadrons in an EAS. We analyzed temporary distribution of pulses of the neutron monitor after a master pulse, given out by the "Carpet" at registration of an EAS. The characteristic time of registration of hadronic component in an EAS is 1 ms. The characteristic size of hadronic EAS core >5 m2 . The essential difference of a multiplicity spectrum of the EAS hadronic component from a background spectrum, connected with galactic cosmic rays of moderate energies is found.
Balabin, Yury; Vashenyuk, Eduard; Dzhappuev, Dakhir
Pathomorphology of esophageal and gastric varices.
In this article, the gross pathology of varices and supplying veins are described comparing esophageal varices and varices of the cardia and fundus of the stomach. The angioarchitecture of the lower esophagus is such that normally very thin parallel veins in the lamina propria mucosae in the palisade zone become enlarged in portal hypertension and join the few larger submucosal veins to form esophageal varices. Enlarged parallel veins come to pile up and join the submucosal veins at an acute angle, rendering this area vulnerable to rupture. Most ruptures occur in this critical area. The basic differences between esophageal and gastric varices are the layers in which the varicose veins form: the lamina propria mucosae and submucosa in the esophageal varices and the submucosa in gastric varices. While cardiac veins and varices are continuous with esophageal varices, fundic varices develop independently as part of a splenogastrorenal shunt that runs through the stomach wall, having rare communications with other veins. The fundic varix is so large in caliber that when it ruptures, the muscularis mucosae and lamina propria are penetrated with massive bleeding. The treatment of varices calls for complete thrombosis of all varicose veins, and merits and demerits of available treatment modalities are discussed based on autopsies from the pathologic point of view. Because of the large size, the management of fundic varices is difficult, and the new technique called balloon-occluded retrograde transvenous obliteration for occluding fundic varices is discussed. PMID:11928080
Arakawa, Masahiro; Masuzaki, Takao; Okuda, Kunio
MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma.
MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors. PMID:24088706
Jin, Zhe; Wang, Liang; Zhang, Yuan; Cheng, Yulan; Gao, Yan; Feng, Xianling; Dong, Ming; Cao, Ziyi; Chen, Si; Yu, Huimin; Zhao, Zhenfu; Zhang, Xiaojing; Liu, Jie; Mori, Yuriko; Fan, Xinmin; Meltzer, Stephen J
EAS selection in the EMMA underground array
NASA Astrophysics Data System (ADS)
The first measurements of the Experiment with MultiMuon Array (EMMA) have been analyzed for the selection of the Extensive Air Showers (EAS). Test data were recorded with an underground muon tracking station and a satellite station separated laterally by 10 metres. Events with tracks distributed over all of the tracking detector area and even extending over to the satellite station are identified as EAS. The recorded multiplicity spectrum of the events is in general agreement with CORSIKA EAS simulation and demonstrates the array's capability of EAS detection.
Sarkamo, J.; Bezrukov, L.; Enqvist, T.; Fynbo, H.; Inzhechik, L.; Joutsenvaara, J.; Kalliokoski, T.; Kuusiniemi, P.; Loo, K.; Lubsandorzhiev, B.; Monto, T.; Petkov, V.; R�ih�, T.; Slupecki, M.; Trzaska, W. H.; Virkaj�rvi, A.
Airway and Esophageal Stenting in Patients with Advanced Esophageal Cancer and Pulmonary Involvement
Background Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. Methods and Findings The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58�\\?8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/?10 weeks and was significantly shorter in group 1 (6+/?7.6 weeks) than in group 2 (28+/?11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. Conclusion Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience.
Paganin, Fabrice; Schouler, Laurent; Cuissard, Laurent; Noel, Jean Baptiste; Becquart, Jean-Philippe; Besnard, Mathieu; Verdier, Laurent; Rousseau, Denis; Arvin-Berod, Claude; Bourdin, Arnaud
Surgical treatment of intractable esophagitis.
An operative technique combining a 360-degree fundoplication which is stabilized by anchoring the gastroesophageal junction to the middle arcuate ligament was used in a series of 140 patients since 1973. The patients were evaluated 1 year or more after surgery with clinical and radiographic assessment, regardless of complaints. Clinical results have been good in 91%. There has been no operative mortality and minor transient morbidity. X-rays done at least 1 year after surgery were compared with results obtained in 88 patients who had a modification of Hill's posterior gastropexy performed during the earlier years of this experience. The incidence of x-ray abnormalities with the posterior gastropexy was reduced from 23.5% to 5% when fundoplication was used in combination with a posterior gastropexy. The anchorage of the esophagogastric junction to the middle arcuate ligament allows a relatively loose fundoplication and thereby has reduced the incidence of disabling gas-bloat. Stabilizing the fundoplication prevents the occurrence of other complications related to fundoplication such as disruption, migration, and obstruction. This technique avoids the use of sutures in the esophageal wall, thus reducing the potential for perforation, fistula, or injury to the vagus nerves.
Gregorie, H B; Cathcart, R S; Gregorie, R J
2011 update on esophageal achalasia
There have been some breakthroughs in the diagnosis and treatment of esophageal achalasia in the past few years. First, the introduction of high-resolution manometry with pressure topography plotting as a new diagnostic tool has made it possible to classify achalasia into three subtypes. The most favorable outcome is predicted for patients receiving treatment for type II achalasia (achalasia with compression). Patients with typeI(classic achalasia) and type III achalasia (spastic achalasia) experience a less favorable outcome. Second, the first multicenter randomized controlled trial published by the European Achalasia Trial group reported 2-year follow-up results indicating that laparoscopic Heller myotomy was not superior to endoscopic pneumatic dilation (PD). Although the follow-up period was not long enough to reach a convincing conclusion, it merits the continued use of PD as a generally available technique in gastroenterology. Third, the novel endoscopic technique peroral endoscopic myotomy is a promising option for treating achalasia, but it requires increased experience and cautious evaluation. Despite all this good news, the bottom line is a real breakthrough from the basic studies to identify the actual cause of achalasia that may impede treatment success is still anticipated.
Chuah, Seng-Kee; Hsu, Pin-I; Wu, Keng-Liang; Wu, Deng-Chyang; Tai, Wei-Chen; Changchien, Chi-Sin
Pharyngeal pump and esophageal transit.
In deglutition the pharynx appears to act as a pump to "inject" boluses into the esophagus. A new method for measuring the velocity profile of the leading edge of a radionuclide bolus has been developed and applied to boluses of different viscosity--water and treacle--in nine normal volunteers. The results show that the more viscous bolus (treacle) acquires a slower initial "injection" velocity (152 mm/sec vs 236 mm/sec) that only propels it over the proximal half of the esophagus. Peristaltic action must drive the bolus over the distal half. With water boluses, however, the higher initial velocity is sufficient to propel a part of the bolus at least to the gastroesophageal junction leaving minimal "work" to be performed by esophageal peristalsis. This confirms the important role of the pharyngeal pump in deglutition. The pump may be the major mechanism for ingestion of nonviscous liquids (water), peristalsis merely being required to "sweep up" what remains in the esophagus. PMID:3665679
Buthpitiya, A G; Stroud, D; Russell, C O
47 CFR 11.44 - EAS message priorities.
Code of Federal Regulations, 2011 CFR
...message priorities. 11.44 Section 11.44 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization � 11.44 EAS message priorities. (a) A national activation of the EAS for a...
47 CFR 11.44 - EAS message priorities.
Code of Federal Regulations, 2010 CFR
...message priorities. 11.44 Section 11.44 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization � 11.44 EAS message priorities. (a) A national activation of the EAS for a...
Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma
In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.
Hyland, Paula L.
Self-expanding plastic stent removed after radiochemotherapy for advanced esophageal cancer.
Endoscopic evaluation after chemoradiotherapy (CR) is impossible with an esophageal stent in place. The main study objective was to evaluate self-expanding plastic stent (SEPS) removal post-CR. Secondary end-points were the improvement of dysphagia and patients' quality of life. From October 2008 to March 2011, 20 dysphagic patients who suffered from advanced esophageal cancer were enrolled in a multicenter, prospective study. SEPS was inserted prior to CR and then removed endoscopically. SEPS efficiency (dysphagia score) and tolerance, as well as the patients' quality of life (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire validated for the esophagus), were monitored. Continuous variables were compared using a paired t-test analysis for matched data. A P-value of less than 0.05 was considered statistically significant. Twenty patients (15 men and 5 women), aged 61.5 years (�9.88) (range 43-82 years), with adenocarcinoma (n = 12) and squamous cell carcinoma (n = 8), were enrolled. SEPS were successfully inserted in all patients (100%). There was one perforation and three episodes of migration. All of these complications were medically treated. The mean dysphagia score at the time of stent placement was 2.79 (0.6). Mean dysphagia scores obtained on day 1 and day 30 post-SEPS placement were 0.7 (0.9) (P < 0.0001) and 0.45 (0.8) (P < 0.0001), respectively. Quality of Life Questionnaire validated for the esophagus score showed an improvement in dysphagia (P = 0.01) and quality of oral feeding (P = 0.003). All SEPS were removed endoscopically without complications. In two patients, the stent was left in place due to metastatic disease. SEPS are extractable after CR of esophageal cancer. Early stenting by SEPS prior to and during CR may reduce dysphagia and improve quality of oral alimentation. PMID:23651038
Laqui�re, A; Grandval, P; Heresbach, D; Prat, F; Arpurt, J P; Bichard, P; D'Halluin, P-N; Berthillier, J; Bousti�re, C; Laugier, R
[Endocervical adenocarcinoma--a current diagnostic problem].
Adenocarcinomas currently account for 15-20% of all invasive carcinomas of the uterine cervix in developed countries. The tumor is asymptomatic in up to 20% of the cases and is usually discovered as result of abnormal Pap smears. Cytology smears however are relatively ineffective in detecting of the cervical adenocarcinoma and its precursors. Today, more effective methods are being implemented for the obtaining and interpretation of cytology smears such as the "liquid based Pap", the "Thin Prep imaging syst". This is required also due to the paucity of trained cytotechnicians and cytopathologists. The introduction of computer assisted system for screening raises the effectiveness of detecting LSIL and HSIL to 37% and 42% respectively The problem however with the diagnosis of cervical adenocarcinoma remains more complicated even with the introduction of the above mentioned techniques for a number of reasons. For instance, there are some morphological differences which delineate it from the squamous carcinoma. In everyday practice the pathologist is faced with the following more important issues surrounding the histologic diagnosis of the cervical adenocarcinoma: (1) the recognition of preivasive glandular lesions; (2) the distinction of preinvasive from invasive adenocarcinoma; (3) the definition and significance of microinvasive adenocarcinoma; (4) the recognition of benign lesion that may mimic adenocarcinoma; (5) the identification and behavior of the most common types of invasive adenocarcinomas. To successfully carry out these tasks the pathologist needs: a good knowledge of the above mentioned problems and a good command of modern ancillary techniques. This paper discusses also some etiologic and risk factors such as sexual activity, parity, smoking and using of oral contraceptives. Particular attention is focused to HPV infection as etiological and diagnostic problem and to distinction of the preinvasive and microinvasive forms of adenocarcinoma. PMID:21434303
Marinova, P; Rampalova, G; Kolnikova, S; Orthova, S; Ondriasch, F
Early esophageal carcinoma treated with intracavitary irradiation
Five patients with early esophageal carcinoma were treated by 6-12 Gy of intracavitary irradiation following 50-60 Gy of external irradiation as a boost therapy. Surgery was not performed in these cases. None of the patients had local recurrence after radiation therapy, as demonstrated by esophagography and endoscopy. Three patients have been alive for 1-3 years 10 months. Esophageal ulceration induced by intracavitary irradiation has occurred in three of the five patients; however, intracavitary irradiation is still a beneficial treatment because of its efficacy in controlling local lesions and because radiation ulceration can eventually be cured. Intracavitary irradiation is recommended to follow external irradiation as a boost therapy for the treatment of early esophageal carcinoma.
Hishikawa, Y.; Tanaka, S.; Miura, T.
Herpetic Esophagitis in Immunocompetent Medical Student
Esophagitis caused by herpes simplex virus (HSV) is often documented during periods of immunosuppression in patients infected with human immunodeficiency virus (HIV); it is rare in immunocompetent diagnosed patients. Case reports of herpetic esophagitis in students of health sciences are extremely rare. The disease presents with a clinical picture characterized by acute odynophagia and retrosternal pain without obvious causes and ulcers, evidenced endoscopically in the middistal esophagus. Diagnosis depends on endoscopy, biopsies for pathology studies, and immunohistochemistry techniques. The disease course is often benign; however, treatment with acyclovir speeds the disappearance of symptoms and limits the severity of infection. In this report, we present a case of herpetic esophagitis in an immunocompetent medical student, with reference to its clinical features, diagnosis, and treatment. The disease may have manifested as a result of emotional stress experienced by the patient.
Marinho, Andreia Vidica; Bonfim, Vinicius Mendes; de Alencar, Luciana Rodrigues; Pinto, Sebastiao Alves; de Araujo Filho, Joao Alves
Bidirectional esophageal dilatation in pharyngoesophageal stenosis postradiotherapy.
Severely stenosed radiation-induced benign strictures around the level of cricopharyngeus post-radical chemoradiation for head and neck or upper esophageal cancers pose significant management problems. We report our technique of bidirectional assessment and dilatation of pharyngoesophageal strictures in patients with an in situ percutaneous endoscopic gastrostomy (PEG) tube. The upper gastrointestinal surgeon approached the area of stenosis in a retrograde manner through the PEG tube to guide the otolaryngeal surgeon who performed anterograde dilatation via a rigid laryngoscope. Between 2005 and 2009, bidirectional esophageal dilatation was performed on 5 patients at our institution. Video fluoroscopy confirmed improved patency of stenosed esophagus in all cases and good improvement in swallowing ability in 4 patients. The ability to accurately assess pharyngoesophageal strictures using bidirectional visualization and transillumination is the key modification of our technique. We suggest using bidirectional esophageal dilatation on difficult cases with severe pharyngoesophageal stenoses although extreme care is required. PMID:22473569
Gavriel, Haim; Duong, Cuong; Spillane, John; Sizeland, Andrew
Mucinous adenocarcinoma of the sublingual gland.
A case of mucinous (colloid) adenocarcinoma of the sublingual gland is reported. Adenocarcinomas associated with large pools of extracellular mucin are extremely rare in the major salivary glands. Analysis of the tumor for cytokeratin expression, estrogen and progesterone receptors was performed. Predominantly, the tumor expressed cytokeratins 7, 8, 18 and 19 that are commonly found in simple epithelia, and to a lesser degree cytokeratins 4 and 13 which are usually found in complex epithelia. Staining for estrogen and progesterone receptors was negative. No other cancer has been detected for three years after the first examination. The tumor is considered to be a primary mucinous adenocarcinoma of the sublingual gland. PMID:9176796
Krogdahl, A S; Schou, C
[Recurrent adenocarcinoma of the uterus].
In a 60-year-old woman because of postmenopausal haemorrhage diagnostic curettage was performed. The histopathologic finding was the adenocarcinoma of the endometrium. The clinical stage was Ib, grade 2 or respectively presumptive stage IV with regard to ultrasound and radiographic findings. After radical hysterectomy and the resection of the sigmoid colon, chemotherapy with cytostatics was applied for 6 months. Three months after chemotherapy the recurrence of the tumour in the vaginal formix and superficial inguinal lymph nodes metastases appeared. Colpectomy with the extirpation of vaginal carcinoma and inguinal lymphadenectomy were performed, followed by irradiation. The course of the disease has shown that when the cancer is located near the point of entry of the uterine tube, the diagnosis and, if needed, therapy should be extended to inguinal regions too. PMID:1875722
Tuskan, E; Lovri?, B; Navratil, I; Tuskan, N
MicroRNAs and esophageal cancer
Cancer of the esophagus is a highly aggressive disease associated with an overall poor prognosis. There is an insistent need for improving our understanding of the molecular basis of this disease. The recent emergence of observations on the role of microRNAs in cancer and their potential as biomarkers has prompted many investigations to examine their relevance to esophageal cancer. This article provides an introduction to microRNA biology and the techniques involved in studying them, and summates what is now known about their role and utility in regard to neoplastic esophageal diseases.
Patnaik, Santosh Kumar; Mallick, Reema
Steroid treatment of eosinophilic esophagitis in adults.
Topical steroid therapy has been used to treat eosinophilic esophagitis (EoE) for more than 15�years. We review the treatment trials of topical steroid therapy in adult patients with EoE. Currently, there is no commercially available preparation designed to deliver the steroid to the esophagus. Current regimens consist of swallowing steroid preparations designed for inhalation treatment for asthma. In the short term, steroids are associated with an approximately 15% to 25% incidence of asymptomatic esophageal candidiasis, but otherwise appear to be well tolerated. PMID:24813521
Alexander, Jeffrey A
Eosinophilic esophagitis: interactions with gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) are not mutually exclusive. The notion that GERD and EoE can be distinguished by the response to proton pump inhibitor (PPI) treatment is based on the mistaken assumption that gastric acid suppression is the only important therapeutic effect of PPIs, and therefore only GERD can respond to PPIs. We believe that a clinical or histologic response to PPIs does not rule in GERD or rule out EoE. We recommend a trial of PPI therapy for patients with symptomatic esophageal eosinophilia, even if the diagnosis of EoE seems clear-cut. PMID:24813513
Cheng, Edaire; Souza, Rhonda F; Spechler, Stuart Jon
Technological advances in radiotherapy for esophageal cancer
Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer. The goal of modern radiotherapy approaches, based on recent technological advances, is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning), reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy), and by better dose delivery to the precisely defined planning target volume (intensity-modulated radiotherapy and proton therapy). Reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in esophageal cancer, although the dose escalation concept is controversial.
Vosmik, Milan; Petera, Jiri; Sirak, Igor; Hodek, Miroslav; Paluska, Petr; Dolezal, Jiri; Kopacova, Marcela
Etiology, diagnosis and treatment of infectious esophagitis
Infectious esophagitis may be caused by fungal, viral, bacterial or even parasitic agents. Risk factors include antibiotics and steroids use, chemotherapy and/or radiation therapy, malignancies and immunodeficiency syndromes including acquired immunodeficiency syndrome. Acute onset of symptoms such as dysphagia and odynophagia is typical. It can coexist with heartburn, retrosternal discomfort, nausea and vomiting. Abdominal pain, anorexia, weight loss and even cough are present sometimes. Infectious esophagitis is predominantly caused by Candida species. Other important causes include cytomegalovirus and herpes simplex virus infection.
Kierzkiewicz, Maciej
Short-term neurodevelopmental outcome of babies operated on for low-risk esophageal atresia: a pilot study.
Data on the neurodevelopmental outcome of esophageal atresia (EA) survivors are scarce, controversial, and based on small samples. This is an observational prospective longitudinal study on a selected cohort of low-risk EA survivors. We considered a low-risk EA survivor a patient with the following characteristics: gestational age >32 weeks, no long gap, no genetic or chromosomic anomaly associated with neurodevelopmental delay, and no further major surgical congenital anomalies. Infants were evaluated with scales derived from the Bayley Scales of Infant and Toddler Development - 3rd Edition at 6 and 12 months, with a score of 100 considered normal for each scale. Analysis of variance was used to assess differences of cognitive and motor development. Linear regression was used to assess the impact of the following clinical and sociodemographic variables: gender, birthweight, gestational age, length of hospital stay, number of surgeries and number of esophageal dilatations during first hospitalization, days of mechanical ventilation, weight at follow up, number of surgeries and esophageal dilatations at follow up, parental age, educational level, and socioeconomic status. Thirty children form the object of the study. The mean (standard deviation [SD]) cognitive scale's score was 93.7 (7.5) and 98.2 (9.6) at 6 and 12 months, respectively (P < 0.05). The mean (SD) motor scale's score was 97.6 (9.3) and 98.0 (12.1) at 6 and 12 months, respectively (P = n.s.). Children with a body weight <5� percentile at 12 months showed a mean (SD) cognitive score significantly lower when compared with those with a body weight >5� percentile: 88.8 (6.3) and 100.5 (8.9), respectively. At 12 months, children with unemployed mothers had a mean (SD) motor score significantly lower when compared with those in the other socioeconomic classes: 87.7 (9.8) and 100.6 (12.4), respectively. In conclusion, parents of babies operated on for low-risk EA can be reassured about neurodevelopmental outcome at least up to 1 year of age. When offering a multidisciplinary follow-up program, underweight patients should deserve particular attention to promote their quality of life and support their global development. PMID:23980587
Aite, L; Bevilacqua, F; Zaccara, A; Rav�, L; Valfr�, L; Conforti, A; Braguglia, A; Bagolan, P
Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study.
The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995-1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27-2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84-1.64) p for trend = 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37-2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91-1.78) p for trend = 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5-<25 kg/m(2)) [HR (95% CI) 0.76 (0.63-0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96-1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90-1.05)]. p for interaction = 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI. PMID:22116732
O'Doherty, Mark G; Freedman, Neal D; Hollenbeck, Albert R; Schatzkin, Arthur; Murray, Liam J; Cantwell, Marie M; Abnet, Christian C
Atmospheric monitoring at the Yakutsk EAS array
NASA Astrophysics Data System (ADS)
There are several instruments at the Yakutsk EAS array which are used for monitoring of atmospheric conditions. Here we present the results of perennial observations of the atmospheric spectral transparency, seasonal variations of aerosol optical depth, stratospheric temperature and ground-level electric field. These characteristics are used during the processing of primary data obtained by the EAS array.
Knurenko, Stanislav; Sabourov, Artem
Laparoscopic Ischemic Conditioning of the Stomach for Esophageal Replacement
Objectives: A considerable percentage of morbidity and mortality after esophagectomy and gastric pull-up is due to leakage of the esophagogastrostomy, which is mainly caused by ischemia of the gastric fundus. Previous clinical studies demonstrated that impaired microcirculation of the gastric conduit almost recovers within the first 5 postoperative days. Therefore, this study was designed to improve gastric perfusion by laparoscopic ischemic conditioning of the stomach. Methods: The study group consisted of 83 patients with 44 esophageal adenocarcinomas and 39 squamous cell carcinomas. A total of 51% received neoadjuvant radiochemotherapy. First, all patients underwent laparoscopic mobilization of the stomach including the cardia and preparation of the gastric conduit. After a mean delay of 4.3 days (range, 3�7 days), a conventional right-sided transthoracic en bloc esophagectomy was performed. Reconstruction was done by gastric pull-up and high intrathoracic esophagogastrostomy. Results: Three conversions (3.6%) to open surgery were necessary during laparoscopic mobilization of the stomach. The reoperation rate was 2.4% (one relaparoscopy for control of a bleeding of the stapler line, one rethoracotomy for chylothorax). Two patients showed circumscribed necroses of the upper part of the fundus after gastric pull-up into the chest. These necroses were resected for reconstruction by esophagogastrostomy. Five patients (6.0%) developed small anastomotic leakages with minor clinical symptoms; however, the gastric conduits were well vascularized. All leakages healed after endoscopic stenting. Major postoperative complications were observed in 13.3% of the patients and the 90-day mortality was 0%. Conclusion: Laparoscopic ischemic conditioning of the gastric conduit is feasible and safe and may contribute to the reduction of postoperative morbidity and mortality after esophagectomy and gastric pull-up.
Holscher, Arnulf H.; Schneider, Paul M.; Gutschow, Christian; Schroder, Wolfgang
Endoscopic therapy of esophageal premalignancy and early malignancy.
Esophageal adenocarcinoma (EAC) is an often deadly cancer with a rising incidence in Western countries. Chronic gastroesophageal reflux disease is associated with the metaplastic transformation of normal squamous epithelium to premalignant specialized intestinal metaplasia within the esophagus (Barrett's esophagus). Barrett's esophagus may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD), or even EAC. Although nondysplastic Barrett's esophagus progresses to EAC at a rate of 0.5% per year, rates of progression for true LGD and HGD are significantly higher. Treatment is mandatory for HGD and may be appropriate in select patients with nondysplastic Barrett's esophagus and many with LGD. Thus, accurate pathologic assessment is necessary before considering endoscopic therapy. Previously, only esophagectomy was offered to patients with HGD or EAC. However, esophagectomy has significant morbidity and mortality, and therefore endoscopic therapies have been advocated for early Barrett's neoplasia. These methods include endoscopic mucosal resection (EMR) and ablative techniques. Ablation techniques include argon plasma coagulation, multipolar electrocoagulation, laser therapy, photodynamic therapy, radiofrequency ablation, and cryotherapy. Of these, radiofrequency ablation has experienced the greatest adoption for the treatment of dysplastic Barrett's esophagus because of excellent published outcomes. The use of EMR to resect suspicious areas or raised lesions is mandatory to provide histology. In contrast, ablation techniques such as radiofrequency ablation have been shown to effectively eradicate large areas of dysplastic tissue with relative ease but do not allow for histologic assessment of the treated area. Combination EMR with radiofrequency ablation is thus advocated to resect visible lesions via EMR (providing histology) and ablate the remainder of the Barrett's esophagus. As always, the appropriate treatment is best determined after careful discussion with patients in a multidisciplinary environment. However, endoscopic therapy offers an attractive alternative to esophagectomy for early Barrett's neoplasia. PMID:21900219
Nealis, Thomas B; Washington, Kay; Keswani, Rajesh N
IgG4-Related Esophageal Disease Presenting as Esophagitis Dissecans Superficialis With Chronic Strictures.
IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform fibrosis and can be associated with tumefactive lesions. IgG4-related disease involving the upper gastrointestinal tract is rare and only two previous case reports have reported IgG4-related esophageal disease. We report the case of a 63-year-old female patient with a long-standing history of severe dysphagia and odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed endoscopic images consistent with esophagitis dissecans superficialis (sloughing esophagitis). An underlying autoimmune process was suspected and immunosuppressant agents were tried to control her disease. The patient eventually developed disabling dysphagia secondary to multiple chronic esophageal strictures. A diagnosis of IgG4-related disease was eventually made after reviewing esophageal biopsies and performing an immunohistochemical study with an anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. Our case report describes this unique case of IgG4-related esophageal disease presenting as chronic esophagitis dissecans with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease. PMID:24883156
Dumas-Campagna, Myriam; Bouchard, Simon; Soucy, Genevieve; Bouin, Mickael
Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas
Gastric Adenocarcinoma With Peritoneal Carcinomatosis; Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis; Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis
Helicobacter pylori Infection and Gastric Adenocarcinoma
Gastric adenocarcinoma is the second leading cause of cancer-related mortality worldwide. Infection with Helicobacter pylori is the strongest recognized risk factor for gastric adenocarcinoma. This bacterial species colonizes the stomach of more than half of the world�s population; however, only a very small proportion of infected subjects develop adenocarcinoma. H. pylori causes a chronic gastritis that may last decades, and a multistep precancerous process is recognized for the most frequent histologic type of gastric adenocarcinoma: the intestinal type. The severity and long-term outcome of this infection is modulated by an increasing list of bacterial, host, and environmental factors, which interplay in a complex manner. Identification of individuals at high risk for gastric cancer that may enter a surveillance program and intervention during the precancerous process is the most suitable strategy for decreasing mortality due to this malignancy.
Correa, Pelayo; Piazuelo, M Blanca
EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer.
Receptor tyrosine kinases (RTKs) are in the focus of targeted therapy for epithelial tumors. Our study addressed the role of EGFR, HER2 and HER3 expression and dimerization in esophageal cancers in situ and in vitro in the context of therapeutic EGFR and HER2 inhibitors. In archival pretreatment biopsies of esophageal carcinomas (n?=?110), EGFR was preferentially expressed in esophageal squamous cell carcinomas (ESCCs) (22.4%; p?=?0.088) and HER2 (34.4%; p?0.001) with HER3 (91.5%; p?0.001) in esophageal (Barrett's) adenocarcinomas (EACs). In situ proximity ligation assays revealed mainly EGFR and HER2 homodimers in ESCC and EAC cases, respectively. However, EAC cases also exhibited HER2/HER3 heterodimers. In vitro ESCC (OE21) cells displayed a significant response to erlotinib, gefitinib and lapatinib, with loss of AKT phosphorylation, G0/G1 cell cycle arrest and induction of apoptosis. In EAC cells (OE19, OE33 and SK-GT-4), lapatinib was similarly effective in strongly HER2-positive (mainly HER2 homodimers and some HER2/EGFR heterodimers) OE19 and OE33 cells. The HER2-targeting antibodies (trastuzumab and pertuzumab) given alone were largely ineffective in ESCC and EAC cells. However, both antibodies significantly induced antibody-dependent cellular cytotoxicity in EAC (OE19 and OE33) cells upon co-culture with peripheral blood mononuclear cells. The study reveals that overexpression of EGFR and HER2 predominantly results in homodimers in ESCCs and EACs, respectively. Still, some EACs also show HER2 dimerization plasticity, e.g., with HER3. Such RTK dimerization patterns affect responses to EGFR and HER2 targeting inhibitors in ESCC and EAC cells in vitro and hence may influence future prediction for particularly HER2-targeting inhibitors in EACs. PMID:24510732
Fichter, Christiane Daniela; Timme, Sylvia; Braun, Julia Alexandra; Gudernatsch, Verena; Sch�pflin, Anja; Bogatyreva, Lioudmilla; Geddert, Helene; Faller, Gerhard; Klimstra, David; Tang, Laura; Hauschke, Dieter; Werner, Martin; Lassmann, Silke
Treatment Modalities for T1N0 Esophageal Cancers: A comparative analysis of local therapy vs. surgical resection
Background In order to investigate the role of non-surgical treatment for early-stage esophageal cancer, we compared the outcomes of local therapy to esophagectomy using a large, national database. Methods Five-year cancer-specific and overall survival of patients with T1N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus treated with either surgery or local therapy with ablative and/or excision techniques in the SEER cancer registry from 1998�2008 were compared using the Kaplan-Meier approach and multivariable and propensity score adjusted Cox proportional-hazard and competing risk models. Results Of 1458 patients with T1N0 esophageal cancer, 1204 (83%) had surgery and 254 (17%) had local therapy only. The use of local therapy increased significantly from 8.1% in 1998 to 24.1% in 2008 (p<0.001). The 5-year overall survival after local excisional therapy and surgery was not significantly different (55.5% vs 64.1% respectively, p=0.07); 5-year cancer-specific survival also did not differ (81.7% vs 75.8%, p=0.10). However, after propensity-score adjustment, cancer-specific survival was better for patients undergoing local therapy compared to surgery (HR: 0.46, 95% CI: 0.27�0.77, p=0.003), while overall survival remained similar. Conclusion The use of local therapy for T1N0 esophageal cancers increased significantly from 1998 to 2008. Compared to esophagectomy, patients treated with local therapy had similar overall survival but improved cancer specific survival, indicating a higher chance of dying from other causes. Further studies are needed to confirm the oncologic efficacy of local therapy when used in patients whose lifespans are not limited by conditions other than esophageal cancer.
Berry, Mark F.; Zeyer-Brunner, Josiane; Castleberry, Anthony W.; Martin, Jeremiah T.; Gloor, Beat; Pietrobon, Ricardo; D'Amico, Thomas A.; Worni, Mathias
Periampullary Adenocarcinoma: Diagnosis and Survival After Pancreaticoduodenectomy
Periampullary adenocarcinomas arise within 2 cm of the major papilla in the duodenum. They arise from different tissues in\\u000a the periampullary region: the head\\/neck\\/uncinate process of the pancreas, the distal common bile duct, the duodenum, and the\\u000a ampulla of Vater. Pancreatic cancer is the most common periampullary adenocarcinoma, followed by distal bile duct cancers,\\u000a ampullary cancers, and duodenal cancers (Jemal
Kanika A. Bowen; Taylor S. Riall
Colonic type adenocarcinoma of male urethra.
A case of rare primary adenocarcinoma of the bulbomembranous portion of the male urethra is presented. The histological and immunohistochemical characteristics of this tumor are identical to those of colon adenocarcinomas. The pathogenesis can be explained either by neoplastic degeneration of globet cells found in the urethral epithelium or by malignant degeneration of persistent glandular elements that are embryonal residues. The patient was successfully treated with transurethral prostatectomy and with a high dose of radiation therapy. PMID:10945163
Baldi, A; Rossiello, R; Di