Section of Digestive Diseases

Indian Hills Cherokee Section, United States

Section of Digestive Diseases

Indian Hills Cherokee Section, United States

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Thrower E.C.,Section of Digestive Diseases | Thrower E.C.,Veterans Administration Connecticut Healthcare | Gorelick F.S.,Section of Digestive Diseases | Gorelick F.S.,Yale University | Gorelick F.S.,Veterans Administration Connecticut Healthcare
Current Opinion in Gastroenterology | Year: 2010

Purpose Of review: This review focuses on studies from the past year that highlight molecular and cellular mechanisms of pancreatic injury arising from acute and chronic pancreatitis. Recent findings: Factors that induce or ameliorate injury as well as cellular pathways involved have been examined. Causative or sensitizing factors include refluxed bile acids, hypercalcemia, ethanol, hypertriglyceridemia, and acidosis. In addition, the diabetes drug exendin-4 has been associated with pancreatitis, whereas other drugs may reduce pancreatic injury. The intracellular events that influence disease severity are better understood. Cathepsin-L promotes injury through an antiapoptotic effect, rather than by trypsinogen activation. In addition, specific trypsinogen mutations lead to trypsinogen misfolding, endoplasmic reticulum stress, and injury. Endogenous trypsin inhibitors and upregulation of proteins including Bcl-2, fibroblast growth factor 21, and activated protein C can reduce injury. Immune cells, however, have been shown to increase injury via an antiapoptotic effect. Summary: The current findings are critical to understanding how causative factors initiate downstream cellular events resulting in pancreatic injury. Such knowledge will aid in the development of targeted treatments for pancreatitis. This review will first discuss factors influencing pancreatic injury, and then conclude with studies detailing the cellular mechanisms involved. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Slivka A.,Hepatology and Nutrition | Gan I.,Digestive Disease Institute | Jamidar P.,Section of Digestive Diseases | Costamagna G.,Policlinico Policlinico Universitario Agostino Gemelli | And 4 more authors.
Gastrointestinal Endoscopy | Year: 2015

Background Characterization of indeterminate biliary strictures remains problematic. Tissue sampling is the criterion standard for confirming malignancy but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed excellent sensitivity in a registry; however, it has not been validated in a prospective study. Objective To prospectively validate pCLE in real time during ERCP for indeterminate biliary strictures. Design Prospective, international, multicenter study. Setting Six academic centers. Patients A total of 136 patients with indeterminate biliary strictures. Interventions Investigators provided a presumptive diagnosis based on the patient history, ERCP impression, and pCLE during the procedure before and after tissue sampling results were available. A presumptive diagnosis also was made separately by a blinded investigator during ERCP and after tissue sampling to estimate care without pCLE. Follow-up was at least 6 months. Main Outcome Measurements Accuracy, sensitivity, and specificity during ERCP alone, ERCP with pCLE, and ERCP with pCLE and tissue sampling. Results A total of 112 patients were evaluated (71 with malignant lesions). Tissue sampling alone was 56% sensitive, 100% specific, and 72% (95% confidence interval [CI], 63%-80%) accurate. pCLE with ERCP was 89% sensitive, 71% specific, and 82% (95% CI, 74%-89%) accurate. After tissue sampling returned, strictures could be characterized with 88% (95% CI, 81%-94%) accuracy. Limitations No randomization of care maps. pCLE not blinded. Conclusion pCLE provided a more accurate and sensitive diagnosis of cholangiocarcinoma compared with tissue sampling alone. Incorporation of pCLE into the diagnostic armamentarium of patients with indeterminate biliary strictures may allow for a more accurate assessment, potentially reducing delays in diagnosis and costly repeat testing. (Clinical trial registration number: NCT01392274.) © 2015 American Society for Gastrointestinal Endoscopy.


Rustagi T.,Section of Digestive Diseases | Corbett F.S.,Sarasota Memorial Hospital | Mashimo H.,Harvard University
Gastrointestinal Endoscopy | Year: 2015

Background Chronic radiation proctopathy (CRP) is a common sequela occurring even many years after pelvic radiation. Current ablative therapies for bleeding ectatic vessels have the potential for deep tissue injury leading to ulcerations, perforation, and fistulas. Radiofrequency ablation (RFA) therapy avoids deep tissue injury and is a promising treatment for CRP. Objective To assess the long-term safety and efficacy of RFA for the treatment of CRP. Design Multicenter, retrospective analysis of a prospectively collected database. Setting Veterans Affairs Boston Healthcare System, Massachusetts; Sarasota Memorial Hospital and Suncoast Endoscopy of Sarasota, Florida. Patients A total of 39 consecutive patients with CRP. Interventions Endoscopic RFA of CRP. Main Outcome Measurements The primary endpoint of the study was complete resolution of rectal bleeding. Secondary endpoints included visually scored improvement of CRP on endoscopic follow-up by using a rectal telangiectasia density (RTD) grading score, improvement in hemoglobin level, and adverse events related to the procedure. Results A total of 39 male patients (mean [± standard deviation {SD}] age 72.9 ± 6.6 years) were included in the study. The mean number of RFA sessions was 1.49 (median 1, interquartile range [IQR] 1-2, range 1-4), with a mean interval of 18 weeks between sessions. Rectal bleeding stopped completely in all patients during the mean follow-up of 28 months (range 7-53 months). A significant improvement occurred in the mean (± SD) hemoglobin level from 11.8 ± 2 to 13.5 ± 1.6 g % (P <.0001). Endoscopic severity also improved significantly with an improvement in the median RTD score from 3 (IQR 2-3) to 0 (IQR 0-1) (P <.0001). Treatment with RFA led to discontinuation of blood transfusion and iron therapy in 92% and 82% patients, respectively. Limitations Retrospective analysis, lack of control group. Conclusion RFA therapy led to complete resolution of rectal bleeding in all treated CRP patients, with improvement in clinical and endoscopic indices without any major adverse events. Further controlled studies are needed to establish RFA as the endoscopic therapy of choice for treatment of CRP. © 2015 American Society for Gastrointestinal Endoscopy.


Kupec J.T.,Section of Digestive Diseases
The West Virginia medical journal | Year: 2011

Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative. Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management.


Loeser C.S.,Section of Digestive Diseases | Robert M.E.,Yale University | Mennone A.,Section of Digestive Diseases | Nathanson M.H.,Section of Digestive Diseases | And 2 more authors.
Journal of Clinical Gastroenterology | Year: 2011

Background and Aims: Current methods to diagnose malignant biliary strictures are of low sensitivity. Confocal endomicroscopy is a new approach that may improve the diagnosis of indeterminate biliary strictures. The purpose of this study was to evaluate indeterminate biliary strictures using probe-based confocal laser endomicroscopy and to understand the histologic basis for the confocal images. Methods: Fourteen patients with indeterminate biliary strictures underwent endoscopic retrograde cholangiopancreatography with examination of their common bile duct with fluorescein-aided probe-based confocal laser endomicroscopy. Standard brushings and biopsies were performed. In parallel, rat bile ducts were examined either with conventional staining and light microscopy or with multiphoton microscopy. Results: Earlier published criteria were used to evaluate possible malignancy in the confocal images obtained in the 14 patients. None of the individual criteria were found to be specific enough for malignancy, but a normal-appearing reticular pattern without other putative markers of malignancy was observed in all normal patients. Multiphoton reconstructions of intact rat bile ducts revealed that the reticular pattern seen in normal tissue was in the same focal plane but was smaller than blood vessels. Special stains identified the smaller structures in this network as lymphatics. Conclusions: Our limited series suggests that a negative confocal imaging study of the biliary tree can be used to rule out carcinoma, but there are frequent false positives using individual earlier published criteria. An abnormal reticular network, which may reflect changes in lymphatics, was never seen in benign strictures. Better correlation with known histologic structures may lead to improved accuracy of diagnoses. Copyright © 2011 by Lippincott Williams & Wilkins.


Reed A.M.,Section of Digestive Diseases | Husain S.Z.,Yale University | Thrower E.,Section of Digestive Diseases | Alexandre M.,Section of Digestive Diseases | And 3 more authors.
Journal of Biological Chemistry | Year: 2011

Low extracellular pH (pHe) occurs in a number of clinical conditions and sensitizes to the development of pancreatitis. The mechanisms responsible for this sensitization are unknown. Because abnormal Ca 2+ signaling underlies many of the early steps in the pathogenesis of pancreatitis, we evaluated the effect of decreasing pHe from 7.4 to 7.0 on Ca 2+ signals in the acinar cell. Low pHe significantly increased the amplitude of cerulein-induced Ca 2+ signals. The enhancement in amplitude was localized to the basolateral region of the acinar cell and was reduced by pretreatment with ryanodine receptor (RYR) inhibitors. Because basolateral RYRs also have been implicated in the pathogenesis of pancreatitis, we evaluated the effects of RYR inhibitors on pancreatitis responses in acidic conditions. RYR inhibitors significantly reduced the sensitizing effects of low pHe on zymogen activation and cellular injury. These findings suggest that enhanced RYR-mediated Ca 2+ signaling in the basolateral region of the acinar cell is responsible for the injurious effects of low pHe on the exocrine pancreas. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Rustagi T.,Section of Digestive Diseases | Mansoor M.S.,Yale New Haven Hospital | Gibson J.A.,Yale University | Kapadia C.R.,Section of Digestive Diseases
Journal of Clinical Gastroenterology | Year: 2015

Pseudomelanosis is a rare finding during upper gastrointestinal endoscopy, and is most commonly seen in the duodenum. Involvement of other organs in the upper gastrointestinal tract is extremely rare, with only 1 reported case involving the stomach, duodenum, and jejunum. We present a case of a 60-year-old woman with mild anemia and hematemesis, who was found to have characteristic speckled pattern of gray-black pigmentation on endoscopic examination. To the best of our knowledge, this is the second reported case of pseudomelanosis involving the stomach, duodenum, and jejunum. © 2014 Wolters Kluwer Health, Inc.


PubMed | Section of Digestive Diseases
Type: Case Reports | Journal: The West Virginia medical journal | Year: 2011

Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1.A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative.Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management.

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