Richard S. Kwon

A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

BACKGROUND Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. RESULTS A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). CONCLUSIONS Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Endoscopic mucosal resection and endoscopic submucosal dissection

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methods are used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the ‘‘related articles’’ feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases data from randomized controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. For this review the MEDLINE database was searched through September 2007 by using the key words ‘‘endoscopic lesion removal,’’ ‘‘endoscopic mucosal resection,’’ ‘‘EMR,’’ ‘‘endoscopic submucosal dissection,’’ and ‘‘ESD.’’ Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

Targeted Imaging of Esophageal Neoplasia with a Fluorescently Labeled Peptide: First-in-Human Results

A fluorescently labeled peptide enables first-in-human targeted endoscopic imaging of esophageal neoplasia. Fluorescent Peptide Probe for Esophageal Cancer Detecting cancerous tissue isn’t always easy—and it can be particularly difficult for the early stages of esophageal cancer because the new lesions are often flat (versus a bulky tumor, for example) and thus invisible to the naked eye. To confidently detect esophageal adenocarcinoma (EAC), Sturm and colleagues designed a fluorescently labeled synthetic peptide, named ASY*-FITC, that recognizes cancer tissue and allows for in vivo imaging with a clinical endoscope. The cancer-targeting ASY*-FITC peptide was discovered using phage display technology and was found to bind tightly to human EAC cells and tissues ex vivo, but not to normal (squamous) tissue or metaplastic tissue, such as Barrett’s esophagus (BE). The tissues identified as cancerous were confirmed via histology. The authors then took this peptide into 25 patients. The fluorescent peptide was administered as would be expected during clinical exam: sprayed on the suspect area and then imaged with an endoscope. No ASY*-FITC bound to the squamous areas, and only minimal amounts of peptide bound to BE. However, areas of EAC as well as a high-grade dysplasia (HGD) were brightly illuminated and easily detected. The peptide was found to be safe and well tolerated in both humans and animals, and was synthesized according to good manufacturing practices (GMPs), suggesting that translation to a clinical setting will be possible in the near future. Further testing is needed to address optical limitations, such as imaging depth. Nevertheless, this first-in-human study paves the way for detection of HGD and EAC and other neoplasias, potentially without invasive biopsy. Esophageal adenocarcinoma is rising rapidly in incidence and usually develops from Barrett’s esophagus, a precursor condition commonly found in patients with chronic acid reflux. Premalignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-human results show that this targeted imaging agent is safe and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

Abstract The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Endoscopic hemostatic devices

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (US Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the ‘‘related articles’’ feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but, in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through September 2008 for articles related to endoscopic hemostatic devices by using the keywords ‘‘multipolar electrocautery,’’ ‘‘bipolar electrocautery,’’ ‘‘heater probe,’’ ‘‘hemostatic grasper,’’ ‘‘argon plasma coagulator,’’ ‘‘injection needle,’’ ‘‘endoloop,’’ ‘‘clip,’’ paired with ‘‘complication,’’ ‘‘perforation,’’ ‘‘peptic ulcer disease,’’ ‘‘gastric antral vascular ectasia,’’ ‘‘Dieulafoy lesion,’’ ‘‘Mallory-Weiss tear,’’ ‘‘radiation induced angioectasias,’’ ‘‘diverticular bleeding,’’ ‘‘angiodysplasia,’’ and ‘‘postpolypectomy bleeding.’’ Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requir-

Confocal laser endomicroscopy

©2014 Blue Cross and Blue Shield of Louisiana An independent licensee of the Blue Cross and Blue Shield Association No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from Blue Cross and Blue Shield of Louisiana. Page 1 of 11 Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the “Company”), unless otherwise provided in the applicable contract. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

Overtube use in gastrointestinal endoscopy.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic, and a MAUDE (Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the ‘‘related articles’’ feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but, in many cases, data from randomized controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the governing board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through March 2009 for articles related to overtube use in GI endoscopy by using the keywords overtube, intubation, enteral access, enteroscopy, and foreign bodies, paired with endoscopy, gastrointestinal. Practitioners should continue to monitor the medical literature for subsequent data about the efficacy, safety, and socioeconomic aspects of these technologies. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

Factors associated with esophageal stricture formation after endoscopic mucosal resection for neoplastic Barrett's esophagus

BACKGROUND EMR for early neoplastic Barretts esophagus is gaining favor over esophagectomy. Esophageal stricture development has been reported as a common complication of EMR, photodynamic therapy, and combination endoscopic therapy. OBJECTIVE To determine clinical and procedural predictors of symptomatic stricture formation after EMR. DESIGN Retrospective analysis. SETTING Tertiary-care referral university hospital. PATIENTS Data were retrospectively reviewed on 73 patients at our institution who underwent EMR monotherapy for Barretts esophagus with high-grade dysplasia or intramucosal cancer since January 2006. INTERVENTION EMR. MAIN OUTCOME MEASUREMENTS Symptomatic esophageal stricture formation. RESULTS Symptomatic esophageal stricture formation was noted in 24.7% of patients undergoing EMR. Stricture formation on univariate analysis was associated with percentage of circumference of esophageal lumen resected, total pieces resected, number of EMR sessions, and tobacco use. A threshold effect was found at 50% of esophageal circumference resected (66.7% vs 27.2% developed strictures above and below the threshold, respectively; P = .004). A 25-pack-year or greater history of tobacco use had a threshold effect on esophageal stricture formation (77.8% vs 7.2% developed strictures above and below the threshold, respectively; P = .02). In multivariate analysis, resection of >50% of the circumference was strongly associated with stricture formation (odds ratio [OR] 4.17; 95% confidence interval [CI], 1.27-13.7). A 25-pack-year or greater history of tobacco use also trended toward stricture formation (OR 3.33; 95% CI, 0.929-12.1). LIMITATIONS Retrospective design, sample size. CONCLUSION Resection of at least 50% of the esophageal mucosal circumference is strongly associated with stricture formation. Patients with strong histories of tobacco use also may be more likely to develop esophageal strictures following EMR.

Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

BACKGROUND Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.

Long-term follow-up of patients with incidentally discovered pancreatic cystic neoplasms evaluated by endoscopic ultrasound

BACKGROUND The management of incidental pancreatic cysts is not well established because of lack of information on their natural history. International Consensus Guidelines advocate observation of asymptomatic patients with small lesions, despite limited data to support this approach. METHODS To characterize clinical outcomes in a cohort of asymptomatic patients with incidental pancreatic cysts who underwent endoscopic ultrasound (EUS) evaluation+/-fine needle aspiration (FNA). RESULTS Overall, 317 patients underwent EUS for evaluation of pancreatic cysts from 1995 to 2005. A total of 97/317 (31%) had asymptomatic, incidentally discovered pancreatic cysts; of 97 asymptomatic patients, 93 were contacted. Of these patients, 71/93 (76%) had lesions<3 cm and benign EUS features. All were followed without operative therapy. The mean follow-up was 44 months (range, 6-123). A total of 69/71 (97%) were alive and free of symptoms of pancreatic disease; 2 patients died of unrelated causes. Among these 71 patients with lesions<3 cm, FNA was performed in 33 patients and cytology was negative for malignant cells in all. Overall, 45/71 patients had either follow-up cross-sectional imaging or EUS. All of them had stable lesions. Surveillance studies were performed with a mean follow-up of 28 months (range, 4-120). The 22 patients with lesions >3 cm and/or concerning EUS features underwent resection. Pathologic analysis revealed that 2/22 patients had adenocarcinoma and that 60% had premalignant lesions. CONCLUSION Endoscopic ultrasound is helpful in evaluation of patients with small incidental pancreatic cystic lesions. Asymptomatic cysts with benign radiographic and/or endosonographic features may safely be followed clinically and with serial imaging.