[Inverted colonic diverticula: an uncommon endoscopic finding]. / Divertículo colónico invertido: un hallazgo endoscópico infrecuente.

BACKGROUND: The appearance of inverted colonic diverticula (ICD) is similar to that of elevated polypoid lesions. The aim of this study was to describe the endoscopic characteristics of ICD with a view to avoiding misdiagnosis, and to report the frequency of these lesions. MATERIAL AND METHOD: Using an endoscopic database, we retrospectively analyzed all patients who underwent colonoscopy at our institution between July 2001 and July 2004. Patients diagnosed with ICD were identified and both patient and ICD characteristics were recorded, including location, endoscopic characteristics, and the presence of synchronous colon polyps. RESULTS: Among the 4508 colonoscopies performed in the selected period, 33 patients (0.7%) were diagnosed with ICD. The mean age was 62.3 years, with a male-to-female ratio of 1:1.2. Most ICD (89%) were in an area of multiple colonic diverticula and 75% were located in the sigmoid colon. One patient had active bleeding directly from the inverted diverticulum and was treated with injection therapy. The endoscopic characteristics of ICDs were described. There were no complications in this series. CONCLUSIONS: ICD is a rare endoscopic finding that can be complicated by local bleeding. Misdiagnosis can be dangerous and biopsy or endoscopic resection could lead to serious complications. The endoscopic criteria described should be considered to avoid the complications associated with biopsy or resection.

Approach to acute, recurrent, and chronic pancreatitis.

Pancreatitis can manifest as a one-time episode, recurring attacks, or chronic pain. It is caused by numerous factors ranging from alcohol consumption to gallstones to subtle obstructive causes and occult autoimmune disorders. As a result, determining the etiology and effectively treating the causes and consequences of pancreatitis can be challenging. This article reviews the diagnosis and management of acute, acute recurrent, and chronic pancreatitis, focusing on more challenging scenarios.

Management of ascending cholangitis.

Acute ascending cholangitis is a potential life-threatening emergency characterized by infection and obstruction of the biliary tree. This article reviews the pathogenesis and clinical approach to patients with ascending cholangitis and examines the literature on this topic.

Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies.

BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet. METHODS: We did two randomised, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and the USA, in HLA-DQ2·5-positive patients aged 18-70 years who had coeliac disease and were on a gluten-free diet. In the screening period for ascending dose cohorts, participants were randomly assigned (1:1) by central randomisation with a simple block method to a double-blind crossover, placebo-controlled oral gluten challenge. Participants with a negative interferon γ release assay to Nexvax2 peptides after the screening oral gluten challenge were discontinued before dosing. For the biopsy cohorts, the screening period included an endoscopy, and participants with duodenal histology who had a Marsh score of greater than 1 were discontinued before dosing. Participants were subsequently randomly assigned to either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts (1:1) by central randomisation with a simple block method. In the three-dose study, participants received either Nexvax2 60 µg, 90 µg, or 150 µg weekly, or placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2 at the maximum tolerated dose (MTD) or placebo. In the 16-dose study, participants received Nexvax2 150 µg or 300 µg or placebo twice weekly over 53 days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD or placebo. In the 4-week post-treatment period, ascending dose cohorts underwent a further double-blind crossover, placebo-controlled oral gluten challenge, which had a fixed sequence, and biopsy cohorts had a gastroscopy with duodenal biopsies and quantitative histology within 2 weeks without oral gluten challenge. Participants, investigators, and study staff were masked to the treatment assignment, except for the study pharmacist. The primary endpoint was the number and percentage of adverse events in the treatment period in an intention-to-treat analysis. Both trials were completed and closed before data analysis. Trials were registered with the Australian New Zealand Clinical Trials Registry, numbers ACTRN12612000355875 and ACTRN12613001331729. FINDINGS: Participants were enrolled from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3, 2012, to Sept 10, 2013, in the 16-dose study. Overall, 62 (57%) of 108 participants were randomly assigned after oral gluten challenge and 20 (71%) of 28 participants were randomly assigned after endoscopy. In the three-dose study, nine participants were randomly allocated to Nexvax2 60 µg and three to placebo (first cohort), nine were allocated to Nexvax2 90 µg and four to placebo (second cohort), eight were allocated to Nexvax2 150 µg and four to placebo (third cohort), and three were allocated to Nexvax2 150 µg and three to placebo (biopsy cohort). In the 16-dose study, eight participants were randomly allocated to Nexvax2 150 µg and four to placebo (first cohort), ten were allocated to Nexvax2 300 µg and three to placebo (second cohort), and seven were allocated to Nexvax2 150 µg and seven to placebo (biopsy cohort). The MTD for Nexvax2 was 150 µg because of transient, acute gastrointestinal adverse events with onset 2-5 h after initial doses of the vaccine, similar to those caused by gluten ingestion. In the ascending dose cohorts in the three-dose study, six (55%) of 11 placebo recipients, five (56%) of nine who received Nexvax2 60 µg, seven (78%) of nine who received Nexvax2 90 µg, and five (63%) of eight who received Nexvax2 150 µg had at least one treatment-emergent adverse event, as did all three (100%) placebo recipients and one (33%) of three Nexvax2 150 µg recipients in the biopsy cohort. In the ascending dose cohorts of the 16-dose study, five (71%) of seven placebo-treated participants, six (75%) of eight who received Nexvax2 150 µg, and all ten (100%) who received Nexvax2 300 µg had at least one treatment-emergent adverse event, as did six (86%) of seven placebo recipients and five (71%) of seven Nexvax2 150 µg recipients in the biopsy cohort. Vomiting, nausea, and headache were the only treatment-emergent adverse events that occurred in at least 5% of participants in either study. Among participants given the MTD, eight gastrointestinal treatment-emergent adverse events occurred in four (50%) of eight participants in the third cohort and none (0%) of three participants in the biopsy cohort in the three-dose study, and five events occurred in five (63%) of eight participants in the first cohort and three events in two (29%) of seven participants in the biopsy cohort of the 16-dose study. Median villous height to crypt depth ratio in distal duodenal biopsies was not significantly different between those who received the vaccine at the MTD on either schedule and those who received placebo. Of the participants who completed the post-treatment oral gluten challenge per protocol, interferon γ release assay to Nexvax2 peptides was negative (responders to treatment) in two (22%) of nine placebo-treated participants in the three-dose study versus two (33%) of six who received Nexvax2 60 µg, five (63%) of eight who received Nexvax2 90 µg, and six (100%) of six who received Nexvax2 150 µg (p=0·007); in the 16-dose study, none (0%) of five placebo-treated participants had a negative assay versus six (75%) of eight who received Nexvax2 150 µg (p=0·021). INTERPRETATION: The MTD of Nexvax2 was 150 µg for twice weekly intradermal administration over 8 weeks, which modified immune responsiveness to Nexvax2 peptides without deterioration in duodenal histology. The gastrointestinal symptoms that followed the first intradermal administration of the vaccine resembled those associated with oral gluten challenge. These findings support continued clinical development of this potential therapeutic vaccine for coeliac disease. FUNDING: ImmusanT.

Endoscopic approach to acute pancreatitis.

This review focuses on the use of endoscopic techniques in the diagnosis and management of pancreatic disorders. Endoscopic retrograde cholangiopancreatography (ERCP) has been used primarily to evaluate and treat disorders of the biliary tree. Recently, endoscopic techniques have been adapted for pancreatic sphincterotomy, stenting, stricture dilation, treatment of duct leaks, drainage of fluid collections, and stone extraction via the major and minor papillae. In patients with acute and recurrent pancreatitis, ERCP carries a higher than average risk of post-ERCP pancreatitis. This risk can be reduced with the placement of a prophylactic pancreatic stent. Magnetic resonance cholangiopancreatography (MRCP) can establish the anatomy of the biliary and pancreatic ducts, identify pancreas divisum or pancreatic ductal strictures, depict bile duct stones, and demonstrate pancreatic or biliary duct dilation. Endoscopic ultrasound (EUS) provides a safer, less invasive, and often more sensitive measure for evaluating the pancreas and biliary tree, and allows some options for therapy. In acute and recurrent pancreatitis, EUS and MRCP can be used to establish a diagnosis; ERCP can be reserved for therapy.

Surgical gastrostomy for pancreatobiliary and duodenal access following Roux en Y gastric bypass.

BACKGROUND: Pancreatobiliary access following Roux-en-Y gastric bypass (RYGBP) is challenging. We reviewed 32 cases of surgical gastrostomy for complex transgastric upper gastrointestinal endoscopy. METHODS: Retrospective review of prospectively collected database of patients with history of RYGBP that had surgical gastrostomy for pancreatobiliary and duodenal access at a single institution from 2004-2008. Indication for procedure, surgical findings, successful cannulation, and complications are reported. RESULTS: Thirty patients (25 female), with age ranging from 27 to 72, underwent 32 procedures. The indications to access the gastric remnant were sphincter of Oddi dysfunction (13), pancreatitis (six), common bile duct stone/obstruction (five), cholangitis (three), pancreatic mass evaluation (two), gastrointestinal bleed (two), and cystic duct leak after cholecystectomy (one). Mean operative time was 200 min (98-338) and estimated blood loss (mean) 85 cc (10-500). Laparoscopic gastrostomy was attempted in 28 cases with one conversion to open (3.6%). Four planned open procedures were also performed. All 30 patients underwent successful endoscopy and 28 had an endoscopic retrograde cholangiopancreatography, all with successful cannulation of the pancreatobiliary tree (100%). CONCLUSIONS: Surgical gastrostomy is an effective means to gain access to the upper GI tract and pancreatobiliary tree following RYGBP. This technique should be considered when traditional endoscopic approaches are impossible.

Technology insight: applications of MRI for the evaluation of benign disease of the pancreas.

This article reviews the role of MRI in the evaluation of benign pancreatic disease. Although MRI and magnetic resonance cholangiopancreatography (MRCP) are most often used to evaluate the liver and bile duct, technical advances such as the use of secretin stimulation also allow for high-quality imaging of the pancreas and pancreatic ductal system. Secretin-stimulated MRCP (S-MRCP) can aid the diagnosis of acute and chronic pancreatitis, and delineate ductal pathology such as benign strictures and duct leaks. There seems to be a role for S-MRCP in the assessment of pancreatic function and (possibly) sphincter of Oddi dysfunction. When endoscopic or surgical therapy is planned, S-MRCP can help to establish a diagnosis as well as offer a 'road map' to guide therapy. S-MRCP is noninvasive and almost entirely without risk to the patient, which gives it a distinct advantage over traditional endoscopic methods of diagnosis for conditions such as pancreas divisum and other ductal pathology. The information provided by S-MRCP, obtained before endoscopic or surgical therapy is attempted, can assist the patient and physician in making a fully informed decision with regard to the risks and probable benefits of any planned intervention.

Microsatellite analysis of sporadic flat and depressed lesions of the colon.

Prior studies of molecular and genetic derangements in flat and depressed lesions of the colon have revealed lower frequencies in a number of markers commonly present in exophytic lesions. These and other differences suggest that flat lesions are driven by alternative pathways. We reviewed a database of patients who had undergone endoscopic mucosal resection (EMR) for flat and depressed lesions at the University of Chicago from January 2001 to April 2003. Formalin-fixed and paraffin-embedded colonic samples were retrieved from the tissue bank, and five standardized mononucleotide and dinucleotide microsatellite regions were analyzed for instability (MSI) using fluorescently labeled forward primers in nonmultiplex reactions. Sixteen patients were identified with flat or depressed lesions who had adequate tissue specimens available for MSI analysis. Of these specimens, eight were tubular adenomas, three were tubulovillous adenomas, and five were carcinomas in situ. Four of the lesions were microsatellite unstable, each at a single locus, and one lesion showed probable instability at a second locus. Eleven lesions were microsatellite stable. Aberrations in DNA repair mechanisms do not appear to significantly contribute to the molecular derangements underlying sporadic flat or depressed colonic lesions. The molecular bases that underlie the aggressive behavior of sporadic flat and depressed lesions remain to be determined, and further investigation is warranted.

Contamination of single-use biopsy forceps: a prospective in vitro analysis.

BACKGROUND: It has been suggested that single-use biopsy forceps prevent interpatient transmission of infection during endoscopy. Passage of sterile forceps through the accessory channel of the endoscope may lead to contamination, however, if the endoscope has been inadequately processed. The potential for contamination of single-use biopsy forceps at various stages of endoscope reprocessing was prospectively evaluated. METHODS: A total of 50 disposable biopsy forceps were passed through the accessory channels of 10 colonoscopes at the following stages of reprocessing: (1) before use in patients to establish a baseline of high-level disinfection, (2) directly after colonoscopy to confirm contamination with use, (3) after manual cleaning and flushing of the accessory channel to support the claim that manual cleaning significantly decreases bioburden, (4) after manual cleaning and a 2-minute soak in 2% glutaraldehyde to assess for contamination after an inadequate cleaning time, and (5) after manual cleaning and a 20-minute soak in 2% glutaraldehyde. The forceps were then sealed in sterile plastic bags after adding 20 mL of thioglycollate broth medium. The suspension was passed through a 0.2-micron vacuum filter and the filters were cultured. All cultures were incubated more than 48 hours. RESULTS: Biopsy forceps underwent a total of 50 aerobic and 50 anaerobic cultures. Colony-forming units too numerous to count of GI flora, including Escherichia coli, Klebsiella, Pseudomonas, and Clostridium species, grew on 19 of 20 culture plates from biopsy forceps passed through colonoscopes immediately after use. One plate in this group grew 3 colony-forming units of E coli. Persistence of GI flora was noted on 5 of 20 plates after manual cleaning of the colonoscopes. No GI flora were found on forceps after the colonoscopes after soaking in gluteraldehyde for 2 and 20 minutes. Environmental contaminants including diptheroids, Staphylococcus, and Streptococcus species grew on 16 culture plates. CONCLUSIONS: (1) Single-use biopsy forceps are highly susceptible to contamination during passage through the accessory channels of improperly cleaned endoscopes. (2) Disinfection of the colonoscopes in this study prevented contamination of the forceps at baseline and after reprocessing. (3) Proper endoscope reprocessing may be the most important factor in preventing biopsy forceps-related interpatient infection.