Priya A. Jamidar

Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial.

IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy. OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief. DESIGN, SETTING, AND PATIENTS Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013. INTERVENTIONS After ERCP, patients were randomized 2:1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1:1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny. MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention. RESULTS Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P = .01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI,19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P = .22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment. CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00688662.

Fellow involvement may increase adenoma detection rates during colonoscopy.

BACKGROUND:Adenoma detection rate (ADR) is increasingly used as a quality indicator for screening/surveillance colonoscopy. Recent investigations to identify factors that affect ADR have focused on the technical aspects of the procedure or the equipment.OBJECTIVE:To assess whether gastroenterology (GI) fellow participation during colonoscopy affects ADR.METHODS:This is a retrospective study of data prospectively collected on 309 patients enrolled in a different study not involving polyp detection. In total, 126 colonoscopies were performed by a GI attending alone, and 183 by a GI fellow supervised by one of the same four GI attendings.RESULTS:The ADR was significantly higher when a fellow was involved (37% vs 23%, P < 0.01), as was the total number of adenomas detected (0.56 per patient vs 0.30 per patient, P < 0.05). The percentage of patients with two and three or more adenomas was also higher for fellows versus attendings alone (13.1% vs 5.6%, and 6% vs 1.6%, respectively; P < 0.05), though there was no difference in the detection of advanced adenomas (7.1% vs 5.6%, P = 0.16). The adenomas detected when fellows participated were smaller (mean size 4.4 mm vs 5.8 mm, P < 0.05), and more likely to be sessile (80.6% vs 64.9%, P < 0.05). There were no significant differences in the age, gender, indication for colonoscopy, or procedure time for the two groups.CONCLUSIONS:In this retrospective study, fellow involvement in colonoscopy may increase not only the ADR, but also the detection of more subtle adenomas. Further investigation into whether this is a “fellow effect,” or simply a matter of more efficient visual scanning and recognition with two people, should be considered.

Pancreatic cancer: a comprehensive review and update.

The term pancreatic cancer encompasses both exocrine and endocrine tumors of the pancreas. More than 90% of pancreatic tumors originate from ductal epithelium and this reviewwill focus only on pancreatic ductal adenocarcinoma, which is commonly referred to as pancreatic cancer. The aim of this review is to update the primary practitioner on the epidemiology, genetics, risk factors, potential for screening, etiology, clinical presentation, diagnosis, and current medical and surgical management of pancreatic cancer.

Confocal Endomicroscopic Examination of Malignant Biliary Strictures and Histologic Correlation With Lymphatics

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.

Oral allopurinol does not prevent the frequency or the severity of post-ERCP pancreatitis.

BACKGROUND Pancreatitis is the most common major complication of ERCP. Efforts have been made to identify pharmacologic agents capable of reducing its incidence and severity. The aim of this trial was to determine whether prophylactic allopurinol, an inhibitor of oxygen-derived free radical production, would reduce the frequency and severity of post-ERCP pancreatitis. Methods A total of 701 patients were randomized to receive either allopurinol or placebo 4 hours and 1 hour before ERCP. A database was prospectively collected by a defined protocol on patients who underwent ERCP. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. RESULTS The groups were similar with regard to patient demographics and to patient and procedure risk factors for pancreatitis. The overall incidence of pancreatitis was 12.55%. It occurred in 46 of 355 patients in the allopurinol group (12.96%) and in 42 of 346 patients in the control group (12.14%; p = 0.52). The pancreatitis was graded mild in 7.89%, moderate in 4.51%, and severe in 0.56% of the allopurinol group, and mild in 6.94%, moderate in 4.62%, and severe in 0.58% of the control group. There was no significant difference between the groups in the frequency or the severity of pancreatitis. CONCLUSIONS Prophylactic oral allopurinol did not reduce the frequency or the severity of post-ERCP pancreatitis.

Analysis of endoscopic management of occluded metal biliary stents at a single tertiary care center

BACKGROUND A significant number of self-expandable metal stents (SEMSs) placed to palliate malignant biliary obstruction will occlude. Few data exist as to what constitutes optimal management. OBJECTIVE Our purpose was to review the management and outcomes of patients with biliary SEMS occlusion. DESIGN AND SETTING Retrospective chart review at a single tertiary care hospital. PATIENTS From January 1999 to October 2005, a total of 90 patients had SEMSs placed for malignant biliary obstruction, and 27 of these occluded. MAIN OUTCOME MEASUREMENTS Technical success of treating SEMS occlusion, stent patency and need for reintervention, and incremental cost analysis. RESULTS A total of 60 ERCPs were performed to treat SEMS occlusions in 27 patients. The success rate was 95%; however, 52% of patients eventually required more than 1 intervention. Placing a second SEMS through the existing SEMS (n = 14) provided the lowest reocclusion rate (43% vs 55% and 100%), the longest time to reintervention (172 days vs 66 and 43 days, P = .03), and a trend toward longer survival (285 days vs 188 and 194 days) compared with plastic stent and mechanical balloon cleaning, respectively. Incremental cost analysis showed both uncovered SEMSs and plastic stents to be cost effective strategies. LIMITATIONS Small number of patients, retrospective study. CONCLUSIONS Treatment of biliary SEMS occlusion with SEMS insertion provides for longer patency and survival, decreases the number of subsequent ERCPs by 50% compared with plastic stents, and is cost-effective.

Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study

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.).

Hybrid natural orifice transluminal endoscopic surgery (NOTES) for Roux-en-Y gastric bypass: an experimental surgical study in human cadavers.

BACKGROUND AND STUDY AIMS The advantages of a hybrid natural orifice transluminal endoscopic surgery approach to Roux-en-Y gastric bypass (hNOTES-RYGBP) might include: easier access to the peritoneal cavity, reduced number of ports and related complications, improved cosmesis, and others. However, currently available conventional endoscopic and laparoscopic instruments might be unsuitable for complex surgical procedures using transluminal access. The aim of this study was to investigate the feasibility and limitations of a NOTES RYGBP. METHODS hNOTES-RYGBP was performed in human cadavers. Pouch creation was achieved by needle-knife dissection using a transvaginal, flexible scope. Articulating linear staplers were placed transumbilically to transect the stomach. Measurements of the small bowel were accomplished intraluminally or with flexible and rigid graspers. New methods were tested to create the gastro-jejunal anastomosis. A linear laparoscopic stapler was used to form the jejuno-jejunal anastomosis. RESULTS Stapler manipulation and anvil docking, bowel manipulation and measurement, and tissue dissection presented the main obstacles for hNOTES-RYGBP. Conventional instruments were too short for some transvaginal manipulations. The time to complete the procedure was 6 - 9 hours. It was feasible to perform a complete hNOTES-RYGBP in four out of seven cadavers. Two cadavers were unsuitable due to anatomical abnormalities or advanced decay. One procedure was terminated before completion because of time constraints. Combinations of flexible and rigid visualization and manipulation were helpful, especially for dissection and gastric pouch creation. CONCLUSIONS Several factors made hNOTES-RYGBP very challenging and time-consuming. A lack of proper instrumentation resulting in insufficient tissue traction, countertraction, and instrument manipulation complicated several steps during the procedure. A combination of flexible with rigid endoscopic techniques offers specific advantages for components of this type of surgery. Changes in instrument design are required to improve more complex endosurgical procedures.

Nurse Observation During Colonoscopy Increases Polyp Detection: A Randomized Prospective Study

OBJECTIVES:To determine whether a second observer during colonoscopy increases adenoma detection.METHODS:Consecutive patients undergoing screening colonoscopy were prospectively randomized to routine colonoscopy or physician and nurse observation during withdrawal.RESULTS:Of 502 patients, 249 were randomized to routine colonoscopy, and 253 to physician plus nurse observation during withdrawal. A total of 592 polyps were detected, 40 identified by the endoscopy nurse only. With nurse observation, 1.32 polyps and 0.82 adenomas were found per colonoscopy, vs. 1.03 polyps and 0.64 adenomas in the routine group, demonstrating a 1.29-fold and a 1.28-fold increase in the average number of polyps and of adenomas detected, respectively. The overall adenoma detection rate (ADR) was 44.1%, with trends toward increased ADR and all-polyp detection rate with nurse observation.CONCLUSIONS:Nurse observation during colonoscopy resulted in an increase in the number of polyps and adenomas found per colonoscopy, along with a trend toward improved overall ADR and all-polyp detection rate.

Chronic pancreatitis, a comprehensive review and update. Part I: epidemiology, etiology, risk factors, genetics, pathophysiology, and clinical features.

Chronic pancreatitis is an irreversible condition of the pancreas characterized by chronic progressive pancreatic inflammation, fibrosis, and scarring resulting in loss of both exocrine (acinar) and endocrine (islet cells) tissue. As the definition implies, it is the inflammation-led fibrosis that culminates in CP. There are several conditions with exocrine insufficiency which need to be distinguished from CP such as post-surgical changes and Shwachman–Diamond Syndrome (the second most common cause for exocrine pancreatic insufficiency in children after cystic fibrosis). The anatomy of the pancreas was first described in the 17th century when the pancreatic duct was discovered (J.C. Wirsung, 1642) and the duodenal papilla was described (J.K. Brunner, 1683; C.B. Holdefreund, 1713; and A. Vater, 1750). The presence of fatty necrosis in acute pancreatitis was first shown by W. Balser (1882), and the autodigestive genesis was suspected by H. Chiari (1896). In 1788, Sir Thomas Cawley of England was the first one to describe on a “free living young man” who had died of diabetes, and on autopsy it was found that the pancreas was filled with multiple calculi. This is the first connection established between diabetes and pancreatitis. Paul Langerhans, who was born in Berlin in to a family of renowned physicians, is well known for pancreatic islets, and dendritic cells of the skin. In 1869, he worked on his PhD thesis on “Abdominal salivary gland” which is now known as the pancreas. During these studies he identified the “small homogeneous islands of clear cells lying throughout the gland.” After his death at the early age of 41 years (from tuberculosis), subsequent researchers magnanimously named these cells as “The islets of Langerhans” (Fig. 1). It was only in 1946 that Comfort et al. described the disease as chronic pancreatitis. Through conferences in Marseille, Cambridge, and Atlanta, the classification of acute and chronic pancreatitis has been revised several times. It has been more than two centuries since