Randomized trial of gastric and colorectal endoscopic submucosal dissection defect closure comparing a novel through-the-scope suturing system with an over-the-scope suturing system (with video).

BACKGROUND AND AIMS: Mucosal closure adds time but reduces adverse events associated with endoscopic submucosal dissection (ESD). We aimed to assess the closure time (CT), technical success, and cost-effectiveness between a novel through-the-scope helix tack suture system (TTSS) and the over-the-scope suturing system (OTSS). METHODS: In this single-center, prospective, randomized trial, all patients undergoing ESD with anticipated closure were randomized 1:1 to TTSS (study group) or OTSS (control group). Primary outcomes were CT and overall CT (OCT; CT + setup time). Secondary outcomes were rates of technical success, adverse events, and cost-effectiveness. RESULTS: Forty patients were randomized to OTSS (n = 20) or TTSS (n = 20). OTSS and TTSS groups were similar with respect to age, gender, proportion of colorectal polyps, proximal colon polyps, and mean size of the resected specimen (40.9 mm vs 40.4 mm). The mean CT was 18.4 minutes for OTSS and 23.3 minutes for TTSS (P = .36). The mean OCT was 32 minutes for OTSS and 39.5 minutes for TTSS (P = .36). Closure with a primary device was successful in 17 cases (85%) with OTSS and 18 cases (90%) with TTSS (P = .63). No closure-related intraprocedural adverse events or delayed perforations were noted. Mean cost of closure was significantly lower in the TTSS group for lesions <35 mm (P = .008). CONCLUSIONS: TTSS was not found to be superior to OTSS with respect to CT and technical and clinical success for closure of gastric and colorectal ESD defects. TTSS is more cost-effective for closure of lesions <35 mm. (Clinical trial registration number: NCT04925271.).

EUS-guided Gastroenterostomy: A Multicenter International Study Comparing Benign and Malignant Diseases.

BACKGROUND: Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is a minimally invasive therapy for patients with gastric outlet obstruction without the risks of surgical bypass and the limited long-term efficacy of enteral self-expanding metal stent placement. However, due to its novelty, there is a lack of significant data comparing long-term outcomes of patients with EUS-GE, based on the underlying disease. In this study, we compare outcomes of EUS-GE on benign versus malignant indications. METHODS: Consecutive patients from 12 international, tertiary care centers who underwent EUS-GE over 3 years were extracted in a retrospective registry. Demographic characteristics, procedure-related information and follow-up data was collected. Primary outcome was the rate of adverse events associated with EUS-GE and the comparison of the rate of adverse events in benign versus malignant diseases. Secondary outcomes included technical and clinical success as well as hospitalization admission. RESULTS: A total of 103 patients were included: 72 malignant and 31 benign. The characteristics of the patients undergoing EUS-GE is shown in Table 1. The mean age of the cohort was 68 years and 58 years for malignant and benign etiology. Gender distribution was 57% and 39% being females in malignant and benign etiology group, respectively. Clinical success, technical success, average procedure time, and hospital length of stay were similar in both groups. Patients with benign underlying etiology had significantly higher number of surgically altered midgut anatomy (P=0.0379). CONCLUSION: EUS-GE is equally efficient regardless of the underlying etiology (malignant vs. benign), and the adverse events both groups were comparable.

Longitudinal outcomes of the endoscopic resection of nonpolypoid dysplastic lesions in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia. According to the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations, "After complete removal of endoscopically resectable nonpolypoid dysplastic lesions, surveillance colonoscopy is suggested rather than colectomy." We sought to add data to the literature and hypothesized that the endoscopic resection of nonpolypoid colorectal dysplasia (NP-CRD) is safe and effective. METHODS: We conducted a retrospective study of a large cohort of patients with IBD at 2 medical centers who underwent colonoscopy between 2007 and 2018. Patients with at least 1 nonpolypoid lesion ≥10 mm were identified. We measured the feasibility of endoscopic resection, incidence of local recurrence, incidence of cancer, need for surgery, and frequency of adverse events. RESULTS: We studied 326 patients who underwent a mean ± standard deviation of 3.6 ± 3.0 (range, 1-16) colonoscopies during a total follow-up of 1208 patient-years. In 36 patients, 161 lesions ≥10 mm were identified, 63 of which were nonpolypoid (mean size, 17.8 ± 8.9 mm; range, 10-45 mm) (prevalence, 7.7%). The majority of nonpolypoid lesions (96.8% [61 of 63]) were managed endoscopically. Four lesions (mean index lesion size, 32.5 ±11.0 mm) had small local recurrences that were successfully retreated with endoscopy. There were no severe adverse events related to IBD or colorectal cancer observed in the follow-up period. CONCLUSIONS: In this IBD cohort, surveillance colonoscopy rather than colectomy was found to be safe and effective in patients with NP-CRD after undergoing endoscopic resection. After complete removal of endoscopically resectable NP-CRD, surveillance colonoscopy should be considered a safe and effective first-line strategy rather than colectomy.

Metastatic Anal Squamous Cell Carcinoma Presenting as an Indeterminate Biliary Stricture Diagnosed By Cholangioscopy.

Anal squamous cell carcinoma (SCC) rarely metastasizes outside the pelvis. Although liver involvement has been described, biliary strictures from metastatic disease are exceedingly rare. We report a case of a patient with metastatic anal SCC presenting as a biliary stricture, which was identified on endoscopic retrograde cholangiopancreatography with single-operator cholangioscopy. Direct visualization of the stricture with single-operator cholangioscopy may prove critical in obtaining a timely diagnosis. Therapeutic options for metastatic anal SCC are limited, but chemotherapy can be considered, and surgical resection is an option for limited disease.

Epiphrenic diverticula: An added source of complexity in achalasia management.

Epiphrenic (pulsion) esophageal diverticula can occur in the setting of underlying esophageal motility disorders such as achalasia and present a unique management challenge to the gastroenterologist. Asymptomatic diverticula do not require treatment, but symptomatic diverticula require therapy targeted to the underlying esophageal motility disorder, or else the diverticula will recur. Generally, laparoscopic or combined laparoscopic/thoracoscopic myotomy, diverticulectomy, and anterior fundoplication are required. However, therapeutic options for epiphrenic diverticula are evolving as peroral endoscopic myotomy (POEM) becomes more commonplace. We review two cases of achalasia complicated by epiphrenic diverticula at our institution. In the first case, type II achalasia was identified and the patient underwent laparoscopic myotomy. In the second case, type III achalasia was present and the patient underwent successful POEM. We discuss the presentation, pathophysiology, and management of epiphrenic diverticula as well as the expanding role for POEM in diverticula.

Lumen apposing metal stents are superior to plastic stents in pancreatic walled-off necrosis: a large international multicenter study.

Background and study aims The use of lumen apposing metal stents (LAMS) during EUS-guided transmural drainage (EUS-TD) of pancreatic walled-off necrosis (WON) has gained popularity. Data supporting their use in WON over plastic stents (PS), however, remain scarce. The aim of this study was to compare the clinical efficacy of LAMS (Axios, Boston Scientific) with PS in WON. Patients and methods This was a multicenter, retrospective study involving 14 centers. Consecutive patients who underwent EUS-TD of WON (2012 - 2016) were included. The primary end point was clinical success defined as WON size ≤ 3 cm within a 6-month period without need for percutaneous drainage (PCD) or surgery. Results A total of 189 patients (mean age 55.2 ±â€Š15.6 years, 34.9 % female) were included (102 LAMS and 87 PS). Technical success rates were similar: 100 % in LAMS and 98.9 % in PS ( P  = 0.28). Clinical success was attained in 80.4 % of LAMS and 57.5 % of PS ( P  = 0.001). Rate of PCD was similar (13.7 % LAMS vs. 16.3 % PS, P  = 0.62), while PS was associated with a greater need for surgery (16.1 % PS vs. 5.6 % LAMS, P  = 0.02). Adverse events (AEs) were observed in 9.8 % of LAMS and 10.3 % of PS ( P  = 0.90) and were rated as severe in 2.0 % and 6.9 %, respectively ( P  = 0.93). After excluding patients with < 6 months follow-up, the rate of WON recurrence following initial clinical success was greater with PS (22.9 % PS vs. 5.6 % LAMS, P  = 0.04). Conclusions When compared to PS, LAMS in WON is associated with higher clinical success, shorter procedure time, lower need for surgery, and lower rate of recurrence.

Lumen-apposing stents versus plastic stents in the management of pancreatic pseudocysts: a large, comparative, international, multicenter study.

BACKGROUND: Larger caliber lumen-apposing stents (LAMSs) have been increasingly used in the management of pancreatic fluid collections, specifically when solid debris is present; however, their advantages over smaller caliber plastic stents in the management of pancreatic pseudocysts are unclear. The aim of this study was to investigate the safety and efficacy of LAMS specifically in the management of pancreatic pseudocysts compared with double-pigtail plastic stents (DPPSs). METHODS: We performed a multicenter, international, retrospective study between January 2012 and August 2016. A total of 205 patients with a diagnosis of pancreatic pseudocysts were included, 80 patients received LAMSs and 125 received DPPSs. Measured outcomes included clinical success, technical success, adverse events, stent dysfunction, pancreatic pseudocyst recurrence, and need for surgery. RESULTS: Technical success was similar between the LAMS and the DPPS groups (97.5 % vs. 99.2 %; P = 0.32). Clinical success was higher for LAMSs than for DPPSs (96.3 % vs. 87.2 %; P = 0.03). While the need for surgery was similar between the two groups (1.3 % vs. 4.9 %, respectively; P = 0.17), the use of percutaneous drainage was significantly lower in the LAMS group (1.3 % vs. 8.8 %; P = 0.03). At 6-month follow-up, the recurrence rate was similar between the groups (6.7 % vs 18.8 %, respectively; P = 0.12). The rate of adverse events was significantly higher in the DPPS group (7.5 % vs. 17.6 %; P = 0.04). There was no difference in post-procedure mean length of hospital stay (6.3 days [standard deviation 27.9] vs. 3.7 days [5.7]; P = 0.31). CONCLUSION: When compared to DPPSs, LAMSs are a safe, feasible, and effective modality for the treatment of pancreatic pseudocysts and are associated with a higher rate of clinical success, shorter procedure time, less need for percutaneous interventions, and a lower overall rate of adverse events.

Endoscopic Mucosal Resection versus Endoscopic Submucosal Dissection for Large Polyps: A Western Colonoscopist's View.

To discuss the rationale for the widespread application of endoscopic mucosal resection (EMR) rather than endoscopic submucosal dissection (ESD) in Western centers. In Western centers, EMR is the treatment of choice for most non-pedunculated colorectal adenomas >2 cm in size. EMR is sufficiently effective and safe to be performed without post-procedure hospitalization. Advances in EMR have led to reduced recurrence rates, and recent studies have demonstrated excellent outcomes with endoscopic treatment of recurrent adenomas. While studies from Asia have demonstrated lower recurrence rates with ESD, concern about the higher perforation risk and lengthy procedure time of ESD are two of the barriers preventing widespread adoption of ESD in the West. EMR is likely to continue as the dominant method for the treatment of large colorectal adenomas in Western centers until the limitations of ESD are overcome.

Combining endoscopic submucosal dissection and endoscopic mucosal resection to treat neoplasia in Barrett's esophagus.

BACKGROUND AND AIMS: Piecemeal endoscopic mucosal resection (EMR) is the standard treatment of nodular Barrett's esophagus dysplasia and T1a cancer. Piecemeal resection may be incomplete and makes precise histologic assessment difficult. Endoscopic submucosal dissection (ESD) is a technique that enables en-bloc resection but has not gained widespread acceptance due to its technical difficulty, risk and long procedure time. METHODS: We developed a protocol consisting of a combination of a limited ESD with supplementary EMR in the same session if necessary, designed to increase en-bloc resection of the most worrisome neoplastic area while maximizing the rate of complete resection of dysplasia. Records of consecutive patients referred for treatment during a 2-year period were reviewed. RESULTS: Eleven patients were treated: two with ESD and nine with combined ESD/EMR. Eight patients had mucosal lesions; three patients had submucosally invasive cancer and were referred to surgery. Five of the 8 mucosal lesions were removed en-bloc by ESD with dysplasia-free margins. Two patients with T1a cancer had low-grade dysplasia in the ESD margins and removal of all dysplasia on EMR. One patient with T1a cancer had high-grade dysplasia in the ESD margins and on EMR. He required a second endoscopy to remove residual neoplasia. There were no adverse events. The mean procedure time was 66.4 ± 15.1 min. CONCLUSIONS: Combining a limited ESD with EMR in the same session enables efficient treatment of visible dysplastic lesions in Barrett's esophagus.

Avulsion is superior to argon plasma coagulation for treatment of visible residual neoplasia during EMR of colorectal polyps (with videos).

BACKGROUND AND AIMS: EMR is used widely for treatment of nonpedunculated colorectal adenomas ≥ 2 cm. Recurrence at the resection site occurs in 10% to 30% of cases. METHODS: Records of consecutive patients referred for endoscopic resection over a 4-year period were reviewed retrospectively. In the first part of the study period, our routine practice was to use argon plasma coagulation (APC) to treat all visible residual neoplasia after exhaustive attempts at snare resection during EMR. In the second part of the study period, we changed our practice to use avulsion to treat all visible residual neoplasia after exhaustive attempts at snare resection during EMR. We analyzed the effect of this change in practice on recurrence rates after EMR. RESULTS: Two hundred twenty-three resected lesions were analyzed. Fifty-nine (26%) were treated with en-bloc EMR, 55 (25%) by piecemeal EMR with complete snare removal of all visible neoplasia, 63 (28%) by piecemeal EMR with APC of visible residual neoplasia, and 46 (21%) by piecemeal EMR with avulsion of visible residual neoplasia. There was no significant difference in adverse event rates among the 4 groups. The recurrence rates on follow-up colonoscopy were 4.2%, 3.0%, 59.3%, and 10.3%, respectively. The recurrence rate for patients treated with avulsion was significantly lower than for those treated with APC (odds ratio, .079; P < .001). Multivariate analysis demonstrated that use of avulsion instead of APC was a significant predictor of no recurrence. CONCLUSIONS: After exhaustive attempts at snare resection during EMR, avulsion is superior to APC for treatment of residual visible neoplasia. Compared with APC, avulsion significantly decreases the recurrence rate without significantly increasing the risk of the procedure.

A radiographic study of the ossification of the posterior wall of the acetabulum: implications for the diagnosis of pediatric and adolescent hip disorders.

BACKGROUND: Subtle variations in acetabular morphology have been implicated in several pathologic hip conditions. Although it is understood that the acetabulum forms at the junction of the ilium, ischium, and pubis at the triradiate cartilage, the ossification and development pattern of the posterior wall of the acetabulum is unknown. Standard radiographs and computed tomographic scans used in evaluation of the adolescent hip do not allow a complete assessment of the non-ossified portions of the developing acetabulum. The purpose of this study was to define the currently unknown ossification pattern and development of the posterior wall of the acetabulum and to determine when conventional imaging, with use of computed tomography and radiographs, is appropriate. METHODS: One hundred and eighty magnetic resonance imaging examinations in patients who were four to fifteen years old were evaluated by a musculoskeletal radiologist for ossification patterns of the posterior wall of the acetabulum and triradiate cartilage. Correlations were made with available radiographs. RESULTS: Posterior acetabular wall ossification lags behind anterior wall ossification throughout development. On average, the posterior wall of the acetabulum began to ossify at the chronological age of eight years, followed by a discrete rim of posterior calcification (posterior rim sign) at the patient age of twelve years, just prior to the fusion of the posterior acetabular wall elements to the pelvis. This preceded the closure of the triradiate cartilage in all subjects. On average, male patients had fusion of the posterior wall of the acetabulum one to 1.5 years after female patients. CONCLUSIONS: The ossification of the posterior wall of the acetabulum is completed in a predictable manner prior to closure of the triradiate cartilage.

Dirichlet multinomial mixtures: generative models for microbial metagenomics.

We introduce Dirichlet multinomial mixtures (DMM) for the probabilistic modelling of microbial metagenomics data. This data can be represented as a frequency matrix giving the number of times each taxa is observed in each sample. The samples have different size, and the matrix is sparse, as communities are diverse and skewed to rare taxa. Most methods used previously to classify or cluster samples have ignored these features. We describe each community by a vector of taxa probabilities. These vectors are generated from one of a finite number of Dirichlet mixture components each with different hyperparameters. Observed samples are generated through multinomial sampling. The mixture components cluster communities into distinct 'metacommunities', and, hence, determine envirotypes or enterotypes, groups of communities with a similar composition. The model can also deduce the impact of a treatment and be used for classification. We wrote software for the fitting of DMM models using the 'evidence framework' (http://code.google.com/p/microbedmm/). This includes the Laplace approximation of the model evidence. We applied the DMM model to human gut microbe genera frequencies from Obese and Lean twins. From the model evidence four clusters fit this data best. Two clusters were dominated by Bacteroides and were homogenous; two had a more variable community composition. We could not find a significant impact of body mass on community structure. However, Obese twins were more likely to derive from the high variance clusters. We propose that obesity is not associated with a distinct microbiota but increases the chance that an individual derives from a disturbed enterotype. This is an example of the 'Anna Karenina principle (AKP)' applied to microbial communities: disturbed states having many more configurations than undisturbed. We verify this by showing that in a study of inflammatory bowel disease (IBD) phenotypes, ileal Crohn's disease (ICD) is associated with a more variable community.

HandAlign: Bayesian multiple sequence alignment, phylogeny and ancestral reconstruction.

UNLABELLED: We describe handalign, a software package for Bayesian reconstruction of phylogenetic history. The underlying model of sequence evolution describes indels and substitutions. Alignments, trees and model parameters are all treated as jointly dependent random variables and sampled via Metropolis-Hastings Markov chain Monte Carlo (MCMC), enabling systematic statistical parameter inference and hypothesis testing. handalign implements several different MCMC proposal kernels, allows sampling from arbitrary target distributions via Hastings ratios, and uses standard file formats for trees, alignments and models. AVAILABILITY AND IMPLEMENTATION: Installation and usage instructions are at http://biowiki.org/HandAlign.

Dopamine D3 receptor antagonists: the quest for a potentially selective PET ligand. Part one: lead identification.

The synthesis and SAR of a new series of potent and selective dopamine D(3) receptor antagonists is reported.

Mapping of conformational epitopes on capsid protein VP2 of infectious bursal disease virus by fd-tet phage display.

Conformational epitopes on VP2 protein of infectious bursal disease virus (IBDV) were mapped using fd-tet phage display. A gene-targeted phage display library was made using DNA fragments ranging approximately from 80 to 400 bp of the hypervariable region of the VP2 gene of IBDV strain 002-73, as neutralizing monoclonal antibodies against the VP2 protein recognize VP2 conformation-dependent epitopes within the hypervariable region. The phages were selected using immobilized monoclonal antibodies. Epitopes on five phages selected with monoclonal antibody 17-82 were located between amino acids 211 and 344. A constructed phage containing amino acids from 204 to 344 strongly reacted with monoclonal antibodies. Compared to that of the constructed phage, the binding of monoclonal antibodies to the five selected phages was dramatically reduced when several amino acids at either terminus or both termini were absent. The binding of a phage, with conversion of the first hydrophilic region into a hydrophobic region as a result of a chance frameshift mutation from amino acids 214 to 225, dropped sharply. It indicates that conformational epitopes may be up to 423 bp long and the commonly suggested fragments of 50-300 bp for making gene-targeted phage display libraries are not long enough to cover the conformational epitopes. This technique can be used to identify the minimum length of the conformational epitopes for developing recombinant vaccines and specific diagnostic tests.

Identification of crucial residues of conformational epitopes on VP2 protein of infectious bursal disease virus by phage display.

A new method for identifying epitopes in viral proteins expressed by filamentous phage has been developed. Filamentous phage fUSE 1 containing the variable region of the VP2 gene of infectious bursal disease virus (IBDV) strain 002-73 was constructed. Neutralizing monoclonal antibodies 17-82 and 33-10 raised against VP2 protein were used to bind phage containing the original variable region of VP2. The phage bound to monoclonal antibodies, were removed by protein G Sepharose and the unbound phage (escape mutants) were isolated for sequencing to locate the mutations. The crucial amino acid residues for conformational neutralizing epitopes recognized by the monoclonal antibodies were located in the first main hydrophilic region (amino acids from 210 to 225) and the central region of the variable region of VP2. The amino acid residues on both ends of the variable region of VP2 affected considerably the binding of monoclonal antibodies. This technique might be useful for selecting escape mutants of phage displaying the original antigenic regions of other viruses to define the crucial amino acid residues of their conformational epitopes, especially viruses that cannot be grown in cell cultures.