Ara Sahakian

Methane and the Gastrointestinal Tract

AbstractIntroductionSeveral gases are produced through enteric fermentation in the intestinal tract. Carbon dioxide, hydrogen, hydrogen sulfide, and methane are thought to be the most common of these. Recent evidence suggests that methane may not be inert. In this review article, we summarize the findings with methane.MethodsThis is a review article discussing the various component gases in the gastrointestinal tract and their relevance to health and disease. Specific attention was paid to understanding methane.ResultsThe majority of these gases are eliminated via flatus or absorbed into systemic circulation and expelled from the lungs. Excessive gas evacuation or retention causes gastrointestinal functional symptoms such as belching, flatulence, bloating, and pain. Between 30 and 62% of healthy subjects produce methane. Methane is produced exclusively through anaerobic fermentation of both endogenous and exogenous carbohydrates by enteric microflora in humans. Methane is not utilized by humans, and analysis of respiratory methane can serve as an indirect measure of methane production. Recent literature suggests that gases such as hydrogen sulfide and methane may have active effects on gut function. In the case of hydrogen sulfide, evidence demonstrates that this gaseous product may be produced by human eukaryotic cells. However, in the case of methane, there is increasing evidence that this gas has both physical and biological effects on gut function. It is now often associated with functional constipation and may have an active role here.ConclusionThis review of the literature discusses the significance of enteric flora, the biogenesis of methane, and its clinical associations. Furthermore, we examine the evidence for an active role of methane in gastrointestinal motility and the potential applications to future therapeutics.

Cold Snare Polypectomy for Large Sessile Colonic Polyps: A Single-Center Experience

Colonoscopic polypectomy has been shown to reduce the risk of colorectal cancer and the mortality. Postpolypectomy bleeding was reported to be lower with cold snare polypectomy (CSP) when compared with conventional polypectomy. CSP has traditionally been utilized only in smaller polyps below 1 cm. We retrospectively analyzed the CSP outcomes in patients with sessile polyps ≥10 mm in size and observed that CSP was feasible in large sessile polyps with no adverse events and with an acceptable rate of residual polyp on follow-up colonoscopy. Further prospective study in larger patient groups is warranted to determine optimal CSP techniques and whether CSP for large polyps has favorable efficacy in regard to complete polypectomy, procedure time, and complication rates relative to polypectomy with cautery.

Randomized Trial of Endoscopist-Controlled vs. Assistant-Controlled Wire-Guided Cannulation of the Bile Duct

OBJECTIVES:Biliary cannulation is frequently the most difficult component of endoscopic retrograde cholangiopancreatography (ERCP). Techniques employed to improve safety and efficacy include wire-guided access and the use of sphincterotomes. However, a variety of options for these techniques are available and optimum strategies are not defined. We assessed whether the use of endoscopist- vs. assistant-controlled wire guidance and small vs. standard-diameter sphincterotomes improves safety and/or efficacy of bile duct cannulation.METHODS:Patients were randomized using a 2 × 2 factorial design to initial cannulation attempt with endoscopist- vs. assistant-controlled wire systems (1:1 ratio) and small (3.9Fr tip) vs. standard (4.4Fr tip) sphincterotomes (1:1 ratio). The primary efficacy outcome was successful deep bile duct cannulation within 8 attempts. Sample size of 498 was planned to demonstrate a significant increase in cannulation of 10%. Interim analysis was planned after 200 patients–with a stopping rule pre-defined for a significant difference in the composite safety end point (pancreatitis, cholangitis, bleeding, and perforation).RESULTS:The study was stopped after the interim analysis, with 216 patients randomized, due to a significant difference in the safety end point with endoscopist- vs. assistant-controlled wire guidance (3/109 (2.8%) vs. 12/107 (11.2%), P=0.016), primarily due to a lower rate of post-ERCP pancreatitis (3/109 (2.8%) vs. 10/107 (9.3%), P=0.049). The difference in successful biliary cannulation for endoscopist- vs. assistant-controlled wire guidance was −0.5% (95% CI−12.0 to 11.1%) and for small vs. standard sphincerotome −0.9% (95% CI–12.5 to 10.6%).CONCLUSIONS:Use of the endoscopist- rather than assistant-controlled wire guidance for bile duct cannulation reduces complications of ERCP such as pancreatitis.

Optimal Timing of Endoscopic Retrograde Cholangiopancreatography in Acute Cholangitis.

Objectives: Acute cholangitis mandates resuscitation, antibiotic therapy, and biliary decompression. Our aim was to define the optimal timing of endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute cholangitis. Methods: Clinical data on all cases of cholangitis managed by ERCP were prospectively collected from September 2010 to July 2013. The clinical impact of the time to ERCP, defined as the time from presentation in the emergency department to the commencement of the ERCP, was determined. The primary outcome was length of hospitalization. Secondary outcomes included vasopressor use, endotracheal intubation, intensive care unit admission, and death. Results: ERCP was successful in 182 (92%) of 199 patients with cholangitis. Length of hospitalization was significantly longer for patients undergoing ERCP at ≥48 versus <48 hours (median 9.1 vs. 6.5 d, P=0.004) even though patients having ERCP at ≥48 hours were less sick as indicated by less frequent intensive care unit admission [odds ratio,0.3; 95% confidence interval (CI), 0.2-0.6]. Multivariate analysis revealed that hospitalization increased by 1.44 days for every day ERCP was delayed (P<0.001). Comparison of ERCP≥72 versus <72 hours revealed odds ratios of 2.6 (95% CI, 1.0-7.0) for vasopressor requirement and 3.6 (95% CI, 0.8-15.9) for mortality. Time to ERCP did not impact technical success or procedural adverse events. Conclusions: ERCP should be performed within 2 days of presentation as a delay of 48 or more hours is associated with disproportionate increase in hospital stay. Delay>72 hours is associated with additional adverse outcomes including hypotension requiring vasopressor support.

The utility of esophagogastroduodenoscopy before endoscopic ultrasonography in patients undergoing endoscopic ultrasonography for pancreatico-biliary and mediastinal indications.

Background: Oblique-viewing echoendoscopes may miss luminal lesions. There is no consensus on whether to routinely perform esophagogastroduodenoscopy (EGD) before endoscopic ultrasonography (EUS). Currently, practice patterns are variable and prospective data are needed. Aim: To determine the proportion of clinically meaningful lesions detected when EGD is performed routinely before EUS. Study: This was a multicenter prospective cohort study conducted at tertiary referral center and large community practice. Patients undergoing EUS for pancreatico-biliary and mediastinal indications were enrolled. Main Outcomes: The primary outcome was the proportion of patients with a clinically meaningful lesion found on EGD. This was a combined outcome defined as any lesion that would alter medical management, or impact the subsequent EUS examination. Results: Two hundred four patients were included in the final analysis. Clinically meaningful lesions were found on EGD in 45 patients [22.1%; 95% confidence interval (CI), 16.4-27.8]. Lesions that altered medical management were found in 32 patients (15.7%; 95% CI, 10.7-20.7). Lesions impacting the subsequent EUS examination were found in 20 patients (9.8%; 95% CI, 5.7-13.9). Clinically meaningful lesions found were (number of patients): esophagitis (14), ulcer (9), ring/stricture (7), large hiatal hernia (6), hyperplastic gastric polyp (5), Barrett esophagus (3), surgically altered anatomy (2), neoplastic lesion (2), subepithelial mass/GIST (1), stenosis (1), diverticulum (1), and fistula (1). Conclusions: EGD before EUS may detect enough clinically meaningful lesions to support the routine performance of EGD before EUS.

Prevention and Management of Post-ERCP Pancreatitis

Pancreatitis remains as one of the most frequent and serious complications of ERCP. Research has identified several patient-related and procedural risk factors, which help guide the endoscopist in prophylaxis and management of pancreatitis. Recent studies have had a major impact on both procedural techniques and pharmacological methods for prophylaxis of post-ERCP pancreatitis. The purpose of this article is to review the relevant literature and describe the most recent and effective approaches in prevention and management of post-ERCP pancreatitis.

Balloon overtube-assisted cholangioscopy and laser lithotripsy of large bile duct stones

ERCP in patients with surgically altered anatomy continues to be challenging. In patients with Roux-en-Y reconstruction, the target site is difficult to reach; the success rates are reported to be as low as 60%. The use of balloon-assisted enteroscopy (BAE) has improved the success rate of ERCP in patients with surgically altered anatomy. The reported success rates of ERCP with BAE range from 64.1% to 98%. In this video, we describe successful balloon overtubeassisted ERCP with single-operator cholangioscopy, laser lithotripsy, and stent placement in a patient with surgically altered anatomy (Video 1, available online at www. VideoGIE.org). An 86-year-old woman with a history of gastric cancer, earlier distal gastrectomy with Roux-en-Y reconstruction, bilateral deep venous thrombosis of the lower limbs with inferior vena cava filter, atrial fibrillation, hypertension, diabetes mellitus type II, and GERD presented with abdominal pain, jaundice, and leukocytosis. A CT scan demonstrated multiple large bile duct stones. All options for intervention, including enteroscopyassisted ERCP, surgery, percutaneous drainage, and EUSguided drainage, were discussed with the patient. She was deemed a poor candidate for surgical intervention or percutaneous intervention. EUS-guided drainage is an accepted alternative for biliary drainage in patients with long-limb anatomy, depending on available expertise. However, given the rate of adverse events with EUSguided hepaticogastrostomy, we reserve this technique as a salvage therapy if enteroscopy is unsuccessful.

Endoscopic Closure of Gastrointestinal Fistulae and Leaks

The development of new endoscopic techniques, such as gastrointestinal (GI) stenting, full-thickness suturing, clip application, and use of tissue adhesives, has had a significant impact on management of GI fistulae. These techniques have shown promising results, but further study is needed to optimize the efficacy of long-term closure. The advancement of endoscopic techniques, including the use of the lumen apposing metal stent (LAMS), has allowed for the deliberate creation of fistula tracts to apply endoscopic therapy that previously could not be achieved. This article examines the rapidly evolving area of endoscopic fistula closure and its relationship to LAMS.

Metallic coil and N-butyl-2-cyanoacrylate for closure of pancreatic duct leak (with video)

BACKGROUND AND AIMS Pancreatic fistula is a challenging yet common adverse event of partial pancreatectomy. Our objective is to determine the feasibility of endoscopic closure of a pancreatic fistula using a combination of a metallic coil and N-butyl-2-cyanoacrylate (NBCA) glue. METHODS A patient with a postoperative pancreatic stump leak recalcitrant to conservative management and pancreatic duct stent placement underwent endoscopic/fluoroscopic placement of a metallic coil in the pancreatic duct followed by injection of .5 mL NBCA and lipiodol mixture directed at the coil. The patients clinical condition, Jackson-Pratt (JP) drain output, and pancreatic enzyme content were monitored daily after the procedure. RESULTS The patients clinical condition improved. JP drain output and amylase/lipase levels progressively decreased to resolution within 7 days of the procedure. No adverse events occurred as a result of the procedure. CONCLUSIONS Endoscopic closure of pancreatic fistula with a metallic coil and NBCA glue is feasible and may be a useful modality for treatment of refractory postpancreatectomy-related fistula.

Endoscopic biopsy and predictors of malignancy in ampullary adenomas: once bitten, twice shy?

Adenomas of the major duodenal papilla are relatively rare, accounting for 5% of gastrointestinal neoplasms.1 Similar to colonic polyps, these tumors are thought to undergo malignant transformation in an adenoma-to-carcinoma sequence.2 This highlights the possibility of curative endoscopic resection and emphasizes the importance of proper staging. Historically, surgical resection has been the mainstay of therapy for ampullary adenomas. Pancreaticoduodenectomy (the Whipple procedure) and transduodenal ampullectomy represent the 2 primary surgical options. Pancreaticoduodenectomy was often favored because of high tumor recurrence rates with local resection.3 Because of the significant morbidity and mortality rates of radical surgical resection, there has been a shift toward endoscopic ampullectomy in carefully selected patients. Ampullary adenomas can be sporadic or associated with familial adenomatous polyposis. It is important to appreciate the fact that ampullary adenomas associated with familial adenomatous polyposis may require more aggressive management because of their high malignant potential. In 2006, the American Society for Gastrointestinal Endoscopy (ASGE) released guidelines describing “The role of endoscopy in ampullary and duodenal adenomas.”4 These guidelines did not offer any criteria for the use of endoscopic ampullectomy as against surgical resection for ampullary adenomas. However, it was stated that the finding of high-grade dysplasia (HGD) warrants therapy, whether it be endoscopic or surgical, because of the high false-negative rate (FNR) of biopsies for carcinoma. HGD was not stated to be a contraindication to endoscopic ampullectomy; however, endoscopic resection of invasive cancer was not endorsed. Given the lack of consensus on the indications for endoscopic ampullectomy, further investigation into this area is greatly desirable. In this issue of the Journal of Clinical Gastroenterology, Kim et al5 present their data on endoscopic biopsies of ampullary adenomas and features that may predict malignancy. The authors retrospectively evaluated 91 cases of ampullary adenoma over a 16-year period diagnosed by endoscopic biopsy, which were resected either endoscopically or surgically. Diagnoses of adenoma were made according to the Vienna classification for gastrointestinal neoplasia. The rate of malignancy (ie, the FNR of endoscopic biopsy) was determined, as was the sensitivity, specificity, and positive and negative predictive value of endoscopic biopsy. Clinical, laboratory, radiologic, and endoscopic findings were analyzed with logistic regression analysis to determine the predictors of carcinoma. Of the 91 subjects initially diagnosed with ampullary adenoma on the basis of endoscopic biopsy, 57 underwent endoscopic ampullectomy and 34 underwent surgical resection. There was 53.8% histopathologic agreement between the initial biopsy specimens and the final resection specimens. Histologic diagnoses were upgraded in 24 lesions (26.4%) from adenoma to carcinoma in situ (Cis) or carcinoma. Multivariate analysis demonstrated that the presence of HGD (OR, 6.66; P=0.012) and ductal dilation (defined as diameter >7mm) (OR, 10.96; P=0.003) was independently associated with Cis/carcinoma in the resection specimen. The presence of one or both of these factors resulted in a sensitivity of 95.8%, specificity of 58.8%, positive predictive value of 52.3%, and negative predictive value of 96.8% for malignancy. When both factors were required, specificity and positive predictive value increased to 96.1% and 84.6%, whereas sensitivity and negative predictive value decreased to 45.8% and 4.5%, respectively. The authors of this study should be commended for providing valuable information on the utility of endoscopic biopsies for ampullary adenomas and for predictors of underlying carcinoma. To date, few data exist regarding the predictors of false-negative biopsies. The primary