The Role of Clips in Preventing Delayed Bleeding After Colorectal Polyp Resection: An Individual Patient Data Meta-Analysis.

BACKGROUND & AIMS: Nonpedunculated colorectal polyps are normally endoscopically removed to prevent neoplastic progression. Delayed bleeding is the most common major adverse event. Clipping the resection defect has been suggested to reduce delayed bleedings. Our aim was to determine if prophylactic clipping reduces delayed bleedings and to analyze the contribution of polyp characteristics, extent of defect closure, and antithrombotic use. METHODS: An individual patient data meta-analysis was performed. Studies on prophylactic clipping in nonpedunculated colorectal polyps were selected from PubMed, Embase, Web of Science, and Cochrane database (last selection, April 2020). Authors were invited to share original study data. The primary outcome was delayed bleeding ≤30 days. Multivariable mixed models were used to determine the efficacy of prophylactic clipping in various subgroups adjusted for confounders. RESULTS: Data of 5380 patients with 8948 resected polyps were included from 3 randomized controlled trials, 2 prospective, and 8 retrospective studies. Prophylactic clipping reduced delayed bleeding in proximal polyps ≥20 mm (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44-0.88; number needed to treat = 32), especially with antithrombotics (OR, 0.59; 95% CI, 0.35-0.99; number needed to treat = 23; subgroup of anticoagulants/double platelet inhibitors: n = 226; OR, 0.40; 95% CI, 0.16-1.01; number needed to treat = 12). Prophylactic clipping did not benefit distal polyps ≥20 mm with antithrombotics (OR, 1.41; 95% CI, 0.79-2.52). CONCLUSIONS: Prophylactic clipping reduces delayed bleeding after resection of nonpedunculated, proximal colorectal polyps ≥20 mm, especially in patients using antithrombotics. No benefit was found for distal polyps. Based on this study, patients can be identified who may benefit from prophylactic clipping. (PROSPERO registration number CRD42020104317.).

Prediction of Polyp Pathology Using Convolutional Neural Networks Achieves "Resect and Discard" Thresholds.

OBJECTIVES: Reliable in situ diagnosis of diminutive (≤5 mm) colorectal polyps could allow for "resect and discard" and "diagnose and leave" strategies, resulting in $1 billion cost savings per year in the United States alone. Current methodologies have failed to consistently meet the Preservation and Incorporation of Valuable endoscopic Innovations (PIVIs) initiative thresholds. Convolutional neural networks (CNNs) have the potential to predict polyp pathology and achieve PIVI thresholds in real time. METHODS: We developed a CNN-based optical pathology (OP) model using Tensorflow and pretrained on ImageNet, capable of operating at 77 frames per second. A total of 6,223 images of unique colorectal polyps of known pathology, location, size, and light source (white light or narrow band imaging [NBI]) underwent 5-fold cross-training (80%) and validation (20%). Separate fresh validation was performed on 634 polyp images. Surveillance intervals were calculated, comparing OP with true pathology. RESULTS: In the original validation set, the negative predictive value for adenomas was 97% among diminutive rectum/rectosigmoid polyps. Results were independent of use of NBI or white light. Surveillance interval concordance comparing OP and true pathology was 93%. In the fresh validation set, the negative predictive value was 97% among diminutive polyps in the rectum and rectosigmoid and surveillance concordance was 94%. DISCUSSION: This study demonstrates the feasibility of in situ diagnosis of colorectal polyps using CNN. Our model exceeds PIVI thresholds for both "resect and discard" and "diagnose and leave" strategies independent of NBI use. Point-of-care adenoma detection rate and surveillance recommendations are potential added benefits.

Community Practice Implementation of a Self-administered Version of PREMM1,2,6 to Assess Risk for Lynch Syndrome.

BACKGROUND & AIMS: Lynch syndrome is a genetic disorder that greatly increases risk for colorectal and other cancers, although it is underdiagnosed. Prediction of MLH1, MSH2, and MSH6 (PREMM1,2,6) is a web-based tool that analyzes individuals' personal/family histories of cancer to quantify their likelihood of carrying a germline mutation associated with Lynch syndrome. We investigated the feasibility of systematic risk assessment for Lynch syndrome in a community gastroenterology practice using a patient-completed version of PREMM1,2,6. METHODS: PREMM1,2,6 was adapted into a computer tablet version designed for self-administration by patients. Individuals presenting to a community gastroenterology office and endoscopy facility in California completed the PREMM1,2,6 assessment before their visit (n = 3134). The total study duration (8 months) comprised a 2-month initiation period (May 1-June 30, 2013) and a 6-month study period (July 1-December 31, 2013). Genetic counseling and germline analysis for mutations in genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM) were offered to individuals with PREMM1,2,6 scores of 5% or higher. Patients and providers completed surveys to evaluate the feasibility and satisfaction with the process. RESULTS: Of the 3134 individuals assessed by PREMM1,2,6 during the 6-month study period, 177 individuals (5.6%) had scores of 5% or higher. Of these, 146 individuals underwent genetic testing, along with 28 additional participants recruited nonconsecutively during the initiation period. Mutations associated with Lynch syndrome were detected in 3 of the 146 individuals (2.1%) with PREMM1,2,6 scores of 5% or higher who underwent germline testing, and 3 of the 28 patients (10.7%) recruited during study initiation with PREMM1,2,6 scores of 5% or higher. Of the participants who underwent genetic analysis, 98.6% stated that they understood the information provided to them. All of the surveyed providers stated that they were satisfied with the incorporation of PREMM1,2,6 into their clinical practice, and that they would continue using it to assess risk for Lynch syndrome. CONCLUSIONS: A patient self-administered version of the PREMM1,2,6 Lynch syndrome risk assessment model can be used systematically in community-based gastroenterology and endoscopy practices.

Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile.

BACKGROUND: Sessile serrated polyps (SSPs) have emerged as important precursors for a large number of sporadic colorectal cancers. They are difficult to detect during colonoscopy due to their flat shape and the excessive amounts of secreted mucin that cover the polyps. The underlying genetic and epigenetic basis for the emergence of SSPs is largely unknown with existing genetic studies confined to a limited number of oncogenes and tumor suppressors. A full characterization of the genetic and epigenetic landscape of SSPs would provide insight into their origin and potentially offer new biomarkers useful for detection of SSPs in stool samples. METHODS: We used a combination of genome-wide mutation detection, exome sequencing and DNA methylation profiling (via methyl-array and whole-genome bisulfite sequencing) to analyze multiple samples of sessile serrated polyps and compared these to familial adenomatous polyps. RESULTS: Our analysis revealed BRAF-V600E as the sole recurring somatic mutation in SSPs with no additional major genetic mutations detected. The occurrence of BRAF-V600E was coincident with a unique DNA methylation pattern revealing a set of DNA methylation markers showing significant (~3 to 30 fold) increase in their methylation levels, exclusively in SSP samples. These methylation patterns effectively distinguished sessile serrated polys from adenomatous polyps and did so more effectively than parallel gene expression profiles. CONCLUSIONS: This study provides an important example of a single oncogenic mutation leading to reproducible global DNA methylation changes. These methylated markers are specific to SSPs and could be of important clinical relevance for the early diagnosis of SSPs using non-invasive approaches such as fecal DNA testing.

Clipping prevents perforation in large, flat polyps.

AIM: To determine if prophylactic clipping of post-polypectomy endoscopic mucosal resection (EMR) mucosal defects of large, flat, right sided polyps prevents perforations. METHODS: IRB approved review of all colonoscopies, and prospective data collection of grasp and snare EMR performed by 2 endoscopists between January 1, 2010 and March 31, 2014 in a community ambulatory endoscopy center. The study consisted of two phases. In the first phase, all right-sided, flat polyps greater than or equal to 1.2 cm in size were removed using the grasp and snare technique. Clipping was done at the discretion of the endoscopist. In the second phase, all mucosal defects were closed using resolution clips. Phase 2 of the study was powered to detect a statistically significant difference in perforation rate with 148 EMRs, if less than or equal to 2 perforations occurred. RESULTS: In phase 1 of the study, 2121 colonoscopies were performed. Seventy-five patients had 95 large polyps removed. There were 4 perforations in 95 polypectomies (4.2%). The perforations occurred in polyps ranging in size from 1.5 cm to 2.5 cm. In phase 2, there were 2464 colonoscopies performed. One hundred and sixteen patients had 151 large polyps removed, and all mucosal defects were clipped. There were no perforations (P = 0.0016). There were no post-polypectomy hemorrhages in either phase. An average of 2.15 clips were required to close the mucosal defects. The median time to perform the polypectomy and clipping was 13 min, and the median procedure duration was 40 min. Five percent of all patients undergoing colonoscopy in our community based, ambulatory endoscopy center had flat, right sided polyps greater than or equal to 1.2 cm in size. CONCLUSION: Prophylactic clipping of the mucosal resection defect of large, right-sided, flat polyps reduces the incidence of perforation.

Radiotherapy dose perturbation of esophageal stents examined in an experimental model.

PURPOSE: To investigate the radiotherapy dose perturbations caused by esophageal stents in patients undergoing external beam treatments for esophageal cancer. METHODS AND MATERIALS: Four esophageal stents were examined (three metallic stents: WallFlex, Ultraflex, and Alveolus; one nonmetallic stent with limited radiopaque markers for visualization: Polyflex). All experiments were performed in a liquid water phantom with a custom acrylic stent holder. Radiochromic film was used to measure the dose distributions adjacent to the stents at locations proximal and distal to the radiation source. The stents were placed in an air-filled cavity to simulate the esophagus. Treatment plans were created and delivered for photon energies of 6 and 15 MV, and data analysis was performed on uniform regions of interest, according to the size and geometric placement of the films, to quantify the dose perturbations. RESULTS: The three metallic stents produced the largest dose perturbations with distinct patterns of "hot" spots (increased dose) measured proximal to the radiation source (up to 15.4%) and both "cold" (decreased dose) and hot spots measured distal to the radiation source (range, -6.1%-5.8%). The polymeric Polyflex stent produced similar dose perturbations when the radiopaque markers were examined (range, -7.6%-15.4%). However, when the radiopaque markers were excluded from the analysis, the Polyflex stent produced significantly smaller dose perturbations, with maximum hot spots of 7.3% and cold spots of -3.2%. CONCLUSIONS: The dose perturbations caused by esophageal stents during the treatment of esophageal cancer using external beam radiotherapy should be understood. These perturbations will result in hot and cold spots in the esophageal mucosa, with varying magnitudes depending on the stent. The nonmetallic Polyflex stent appears to be the most suitable for patients undergoing radiotherapy, but further studies are necessary to determine the clinical significance of the dose perturbations.