Faculty Bibliography

PURPOSE: Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology. We, therefore, examined the presence and extent of genomic instability in advanced and less advanced BE histology using mutational load (ML). METHODS: ML summarized the presence and clonality of loss of heterozygosity (LOH) mutations and the emergence of new alleles, manifested as microsatellite instability (MSI) mutations, in ten genomic loci around tumor suppressor genes associated with EAC. The ML of 877 microdissected targets from BE biopsies was correlated to their histology. Histological targets were categorized into three levels: no ML, low ML, and high ML. RESULTS: Increasing ML correlated with increasingly severe histology. By contrast, proportions of targets that lacked mutations decreased with increasingly severe histology. A portion of targets with non-dysplastic and low-grade histology shared a similar ML as those with higher risk and EAC disease. The addition of MSI characterization to ML helped to differentiate the ML between advanced and less advanced histology. CONCLUSIONS: Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC. ML may help to better manage BE in early histological stages and when histology alone provides insufficient information.

Objectives: Colonoscopy is the gold standard for colon cancer screening, by detecting and removing adenomatous polyps. However, polyps can be missed in the proximal mucosal folds with traditional forward viewing colonoscopy. The ARC EndoCuff is a disposable attachment placed on the tip of the colonoscope. With soft, hair-like projections, the EndoCuff (Image 1.) helps to flatten colon mucosal folds during scope withdrawal allowing for increased mucosal inspection. A new technique often has to allow for proficiency and the aim of our study is to assess the learning curve for EndoCuff by comparing adenoma detection rate (ADR) with successive weeks of operator experience. Methods: We retrospectively analyzed patients who underwent colonoscopy with Endocuff for any indication at an outpatient urban practice over a 3-week period. ADR was calculated for each week and weeks 2 and 3 were compared to week 1, which served as our control. Total number of EndoCuff procedures in week 1 were divided by total number of operators to determine the average procedures needed to overcome the learning curve. Colonoscopy reports were retrospectively reviewed and paired t-tests were performed to assess for significance between ADR for each week. Results: A total of 58 patients underwent EndoCuff during the 3-week period. A total of 15, 21, and 22 patients had procedure performed in weeks 1,2, and 3, respectively (Table 1.). A total of 4 operators participated in week 1 and number of procedures ranged from 2 to 5 with a mean of 3.75. ADR for week 1 was 20% which increased to 54.5% in week 2 (p=0.03) and reached its peak at 63.6% in week 3 (p=0.004). Given the significant improvement in week 2 compared to week 1, learning curve was approximated to be 4 procedures based on a total of 15 procedures performed in week 1 divided amongst four operators. Conclusions: Our results suggest that a learning curve does exists for EndoCuff and that ADR significantly increases with operator experience after 4 procedures. Overall, End!

Objectives: Colonoscopy is the gold standard for colon cancer screening and prevention. Several new technologies have recently emerged in order to better assist gastroenterologists in their evaluation of the colonic mucosa to find and remove polyps during screening and surveillance colonoscopies. The ARC EndoCuff is a disposable plastic device with soft, hair-like projections that is placed at the tip of the colonoscope prior to the procedure (Image 1.). The device helps to stabilize the tip of the colonoscope and assists in flattening the folds of the colonic mucosa in order to better evaluate proximal colonic folds. We performed a retrospective chart review of patients who underwent screening and surveillance colonoscopy with and without EndoCuff. The aim of our study was to assess whether EndoCuff was more effective at detecting polyps and adenomas. Methods: Patients were retrospectively analyzed at a tertiary care medical center, urban and suburban outpatient practices from September 2013 thru November 2013. Only screening and surveillance colonoscopies were included. Based on previous learning curve results, the first 4 EndoCuff procedures for each operator were excluded. A comparison group was matched to Endocuff cases based on indication. Colonoscopy reports were retrospectively reviewed to obtain demographic information, total polyps and adenomas removed. This was used to calculate overall ADR and ADR by colon location (right vs. left). Paired t-tests were performed to assess for significance between EndoCuff and comparison group with respect to total polyps and adenomas removed and ADR. Results: 165 patients received EndoCuff and 153 patients underwent standard colonoscopy. Average polyps detected per patient in the EndoCuff group was 1.31 vs. 0.82 in standard colonoscopy (p=<0.001). Similar results were also observed in average adenoma per patient 0.8 vs 0.38 (p=<0.001). The ADR was highest amongst patients who underwent EndoCuff compared to standard colonoscopy (46.6% vs. 30.0%, p=0.!

Background: Barrett's esophagus (BE) is a pre-cancerous condition characterized by esophageal goblet cell metaplasia which can progress to dysplasia and ultimately adenocarcinoma. The gold standard for diagnosis is the modified Seattle protocol, where 4 quadrant forceps biopsies (FB) are taken at least every 2 centimeters (cm) throughout the BE segment. This method leaves a large amount of unsampled tissue which could be harboring more advanced dysplasia or neoplasia than what was obtained on FB. Wide Area Transepithelial Sampling (WATS3D) has been shown to increase the detection of both BE and dysplasia. The aim of this study is to estimate the adjunctive yield of WATS3D to FB across multiple community-based gastroenterology practices. Methods: Patients with GERD, possible BE or proven BE underwent upper endoscopy with 1 of 28 gastroenterologists. WATS3D biopsies were obtained using the standard 2-brush technique (EndoCDx, CDx DiagnosticsTM, Suffern, NY). Additional FB also were obtained during the same endoscopy following brush biopsy. Brush and forceps samples were sent together to a central laboratory. WATS3D samples were analyzed using a neural network to identify goblet cell metaplasia and dysplasia. FB samples underwent standard histologic review. Both sample sets were evaluated by trained GI pathologists. De-identified data was aggregated for analysis. Results: A total of 2559 patients underwent upper endoscopy with submission of WATS3D samples and FB, though 2498 specimen sets were included in the final analysis. Patients were 60% female, with an average age of 55 years (15-97). The most common indication for endoscopy was gastroesophageal reflux disease. In 80% of cases, the suspected Barrett's length was less than 3 cm. FB identified BE in 377 cases (15.1%), and dysplasia was seen in 17 of these cases (4.51% of BE, 0.68% of all FB). Adjunctive use of WATS3D identified an additional 258 cases of BE, increasing the diagnostic sampling yield by 68.4% to 25.4%. WATS3D also detected an ad!

Background: Patients with Barrett's esophagus (BE) are enrolled in surveillance programs for the detection of dysplasia and/or early cancer and undergo 4 quadrant biopsies every 1-2 cm. The histopathological diagnosis of BE associated dysplasia has poor inter-observer agreement even amongst experienced GI pathologists. Published estimates for the inter-observer agreement (kappa values) in the reading of dysplasia in Barrett's esophagus have varied between 0.36-0.78. The WATS procedure uses a minimally invasive brush biopsy technique for acquiring wide area sampling of BE tissue. The analysis of the WATS sample is aided by a high speed computer scan which identifies potentially abnormal cells, cell clusters and abnormal glandular cells on a high resolution video monitor for pathologists to review. Approximately 200 "most suspicious" cells are then flagged by the computer as a starting point for analysis. However, the inter-observer agreement amongst pathologists using the WATS samples has not been performed. Aim: To assess inter-observer agreement among pathologists in the diagnosis of Barrett's esophagus and dysplasia using the WATS computer-assisted analysis technique. Methods: WATS slides with varying degrees of BE dysplasia were randomly selected and distributed to four pathologists trained in the analysis of WATS samples. Each pathologist completed a standardized CRF for each BE slide evaluated grading them as non-dysplastic, low-grade dysplasia (LGD) or highgrade dysplasia/esophageal adenocarcinoma (HGD/EAC). Using the published range of kappa values for histopathological diagnosis, we assumed a minimal acceptable level of reliability (pO) of 0.35 and an expected rho value (p1) of 0.55. A sample size of 60 slides using 3 reviewers would be sufficient to maintain a power of 80% with an alpha of 0.05. The kappa values were graded based on Landis and Koch scale (kappa values: 0.41 to 0.60 indicate moderate agreement, 0.61 to 0.80 indicate substantial agreement, and above 0.80 indicate nearly !

Endoscopic esophageal stent placement is widely used in the treatment of a variety of benign and malignant esophageal conditions. Self expanding metal stents (SEMS) are associated with significantly reduced stent related mortality and morbidity compared to plastic stents for treatment of esophageal conditions; however they have known complications of stent migration, stent occlusion, tumor ingrowth, stricture formation, reflux, bleeding and perforation amongst others. A rare and infrequently reported complication of SEMS is stent fracture and subsequent migration of the broken pieces. There have only been a handful of published case reports describing this problem. In this report we describe a case of a spontaneously fractured nitinol esophageal SEMS, and review the available literature on the unusual occurrence of SEMS fracture placed for benign or malignant obstruction in the esophagus. SEMS fracture could be a potentially dangerous event and should be considered in a patient having recurrent dysphagia despite successful placement of an esophageal SEMS. It usually requires endoscopic therapy and may unfortunately require surgery for retrieval of a distally migrated fragment. Early recognition and prompt management may be able to prevent further problems.

There has been limited research examining the risks, benefits, and use of common endoscopic procedures in the elderly. Furthermore, gastroenterology training programs do not routinely incorporate elderly concerns when dealing with common gastrointestinal issues. There exists a broad array of endoscopic procedures with varying inherent risks that must be weighed with each elderly patient in mind. This article discusses the benefits and drawbacks of the most common procedures and indications for endoscopy including upper endoscopy, colonoscopy, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, percutaneous endoscopic gastrostomy, and deep enteroscopy.