ASGE principles of endoscopic training.

This White Paper shares guidance on the important principles of training endoscopy teachers, the focus of an American Society for Gastrointestinal Endoscopy (ASGE)/World Endoscopy Organization Program for Endoscopic Teachers and Leaders of Endoscopic Training held at the ASGE Institute for Training and Technology. Key topics included the need for institutional support and continuous skills development, the importance of consensus and consistency in content and approach to teaching, the role of conscious competence and content breakdown into discreet steps in effective teaching, defining roles of supervisors versus instructors to ensure teaching consistency across instructors, identification of learning environment factors and barriers impacting effective teaching, and individualized training that incorporates effective feedback and adapts with learner proficiency. Incorporating simulators into endoscopy teaching, applying good endoscopy teaching principles outside the endoscopy room, key principles of hands-on training, and effective use of simulators and models in achieving specific learning objectives were demonstrated with rotations through hands-on simulator stations as part of the program. A discussion of competency-based assessment was followed by live sessions in which attendees applied endoscopy teaching principles covered in the program. Conclusions highlighted the need for the following: formal training of endoscopy teachers to a level of conscious competence, incorporation of formal training structures into existing training curricula, intentional teaching preparation, feedback to trainees and instructors alike aimed at improving performance, and competency-based trainee assessment. The article is intended to help motivate individuals who play a role in training other endoscopists to develop their teaching abilities, promote discussions about endoscopy training, and engage both endoscopy trainers and trainees in a highly rewarding learning process that is in the best interest of patients.

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.

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.

Spectrum of use and effectiveness of endoscopic and surgical therapies for chronic pancreatitis in the United States.

OBJECTIVE: This study aims to describe the frequency of use and reported effectiveness of endoscopic and surgical therapies in patients with chronic pancreatitis treated at US referral centers. METHODS: Five hundred fifteen patients were enrolled prospectively in the North American Pancreatitis Study 2, where patients and treating physicians reported previous therapeutic interventions and their perceived effectiveness. We evaluated the frequency and effectiveness of endoscopic (biliary or pancreatic sphincterotomy, biliary or pancreatic stent placement) and surgical (pancreatic cyst removal, pancreatic drainage procedure, pancreatic resection, surgical sphincterotomy) therapies. RESULTS: Biliary and/or pancreatic sphincterotomy (42%) were the most common endoscopic procedure (biliary stent, 14%; pancreatic stent, 36%; P < 0.001). Endoscopic procedures were equally effective (biliary sphincterotomy, 40.0%; biliary stent, 40.8%; pancreatic stent, 47.0%; P = 0.34). On multivariable analysis, the presence of abdominal pain (odds ratio, 1.82; 95% confidence interval, 1.15-2.88) predicted endoscopy, whereas exocrine insufficiency (odds ratio, 0.63; 95% confidence interval, 0.42-0.94) deterred endoscopy. Surgical therapies were attempted equally (cyst removal, 7%; drainage procedure, 10%; resection procedure, 12%) except for surgical sphincteroplasty (4%; P < 0.001). Surgical sphincteroplasty was the least effective (46%; P < 0.001) versus cyst removal (76% drainage [71%] and resection [73%]). CONCLUSIONS: Although surgical therapies were performed less frequently than endoscopic therapies, they were more often reported to be effective.

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.

Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis.

BACKGROUND & AIMS: Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. METHODS: We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). RESULTS: The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. CONCLUSIONS: The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP.

Improved diagnosis of pancreatic adenocarcinoma using haptoglobin and serum amyloid A in a panel screen.

BACKGROUND: Timely, accurate diagnosis of pancreatic adenocarcinoma (PA) is hampered by the lack of effective circulating biomarkers. No single test has emerged that improves upon the commonly used biomarker cancer antigen 19-9 (CA 19-9) to discriminate PA from benign conditions effectively. The goals of this study were to validate two acute-phase proteins, haptoglobin and serum amyloid A (SAA), as biomarkers for PA and determine if the combination of haptoglobin, SAA, and CA 19-9 would improve PA diagnosis over CA 19-9 alone. METHODS: Levels of haptoglobin, SAA, and CA 19-9 were measured in pretreatment sera from 75 PA patients, 32 patients with chronic pancreatitis, 42 patients with other benign pancreatic disease or biliary stricture, and 150 healthy control subjects by enzyme-linked immunosorbent assay or colorimetric binding assay. Relative levels of haptoglobin or SAA were compared between groups using analysis of variance. The diagnostic accuracy of serum haptoglobin and SAA levels were investigated using receiver operating characteristics (ROC) analysis. Using classification tree analysis, an algorithm was developed that used haptoglobin, SAA, and CA 19-9 in a diagnostic screening panel. RESULTS: Both haptoglobin and SAA were significantly elevated in sera from PA patients compared to healthy control subjects (p<0.0001) and patients with chronic pancreatitis (p=0.01). Haptoglobin was significantly elevated in sera from PA patients relative to patients with other benign diseases (p=0.0015), whereas SAA fell short of significance in the same comparison (p=0.0508). ROC analysis indicated that haptoglobin [area under the curve (AUC)=0.792] was a better diagnostic marker than SAA (AUC=0.691) over multiple threshold cutoffs. Using specific cutoffs that minimized overall misclassification, haptoglobin yielded a sensitivity of 82.7% and a specificity of 71.1%, and SAA yielded a sensitivity of 34.7% and a specificity of 90.2% when discriminating PA cases from all non-PA controls. In the same sample set, CA 19-9 yielded a sensitivity of 77.3% and a specificity of 91.1%. Combining data from haptoglobin, SAA, and CA 19-9 in a diagnostic screening panel improved the overall accuracy when compared to CA 19-9 alone, yielding a sensitivity of 81.3% and a specificity of 95.5%. CONCLUSIONS: These data demonstrate that haptoglobin and SAA are useful for discriminating PA from benign conditions as well as healthy controls when used in a diagnostic screening panel. This study supports the use of combined biomarkers for improved accuracy in the diagnosis of PA.

Plastic versus self-expanding metallic stents for malignant hilar biliary obstruction: a prospective multicenter observational cohort study.

BACKGROUND: There are few comparative data as to whether plastic or self-expanding metallic stents are preferable for palliating malignant hilar biliary obstruction. METHODS: Thirty-day outcomes of consecutive endoscopic retrograde cholangiopancreatographies performed for malignant hilar obstruction at 6 private and 5 university centers were assessed prospectively. RESULTS: Patients receiving plastic (N=28) and metallic stents (N=34) were similar except that metallic stent recipients more often had: Bismuth III or IV tumors (16/34 vs. 5/28 P=0.043), higher Charlson comorbidity scores (P=0.003), metastatic disease (P=0.006), and management at academic centers (P=0.018). The groups had similar rates of bilateral stent placement (4/28 vs. 5/34), and similar frequency of opacified but undrained segmental ducts (7/28 vs. 5/34). Adverse outcomes including cholangitis, stent occlusion, migration, perforation, and/or the need for unplanned endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography occurred in 11/28 (39.3%) patients with plastic versus 4/34 (11.8%) with metal stents (P=0.017). By logistic regression, factors associated with adverse outcomes included plastic stent placement (odds ratio 6.32; 95% confidence interval 1.23, 32.56) and serum bilirubin (1.11/mg/dL above normal: 1.01, 1.22) but not center type or Bismuth class. CONCLUSIONS: Metallic stent performance was superior to plastic for hilar tumor palliation with respect to short-term outcomes, independent of disease severity, Bismuth class, or drainage quality.

DPEJ tube placement prevents aspiration pneumonia in high-risk patients.

Percutaneous endoscopic gastrostomy (PEG) or PEG tube with transgastric jejunostomy tube (PEG-J) feeding has not been shown to decrease aspiration pneumonia. The aim of this study was to determine if direct percutaneous endoscopic jejunostomy (DPEJ) tube placement results in a decreased incidence of aspiration pneumonia in high-risk patients. The design was a retrospective review of all patients receiving DPEJ tube for aspiration pneumonia from 1999 to 2005. Demographics, incidence of aspiration pneumonia, and outcomes were collected and compared before and after the DPEJ placement. Eleven patients (4 women, 7 men) were identified; their mean age was 44.9 years (range, 18-94 years). The etiologies for recurrent aspiration pneumonia were neurologic disease (9), esophageal surgery (1), and severe debilitation (1). The mean follow-up was 20.9 months (range, 6-48 months). The patients' mean weight increased from 43.8 kg (range, 19-55 kg) to 48.3 kg (range, 30-65 kg) after placement (P < .001). The total number of documented aspiration pneumonia episodes for all patients decreased from 29 (mean, 3.64; range, 1-6) before DPEJ placement to 3 (mean, 0.27; range, 0-2) after DPEJ placement (P < .001). The mean number of aspiration pneumonia events per month prior to the DPEJ placement was 3.39 and postplacement was 0.42 (P < .001). DPEJ placement appears to decrease recurrent aspiration pneumonia in patients with history of aspiration pneumonia.

A randomized, prospective trial of electrosurgical incision followed by rabeprazole versus bougie dilation followed by rabeprazole of symptomatic esophageal (Schatzki's) rings.

BACKGROUND: Lower esophageal (Schatzki's) rings are a common cause of solid food dysphagia. Standard treatment involves passage of a single large bougie to disrupt the ring, but symptoms recur in the majority of patients. Electrosurgical incision of the ring may provide a longer duration of symptom improvement. There are no data on the treatment of Schatzki's rings in the presence of acid suppression treatment. OBJECTIVE: Our purpose was to compare the efficacy of bougie dilation with electrosurgical incision of symptomatic Schatzki's rings at 1-year follow-up in the presence of rabeprazole treatment. DESIGN: Randomized, prospective trial. SETTING: University of Utah Health Sciences Center and the Veterans Affairs Salt Lake. PATIENTS: Fifty patients referred for endoscopic evaluation of dysphagia between January 2002 and March 2005. MAIN OUTCOME MEASUREMENTS: Symptom-free survival time (in months), dysphagia, and GERD scores. RESULTS: Twenty-five patients each underwent bougie dilation and electrical incision and were followed up for 12 months. Symptom-free survival times were significantly longer in the incision group (7.99 months) compared with the bougie dilation group (5.86 months) (P = .03). Dysphagia and GERD scores significantly improved in each group comparing baseline with each time interval. The incision group had greater relief of dysphagia at 1 month (P = .05) compared with the bougie group. There was no difference between GERD scores in both groups. LIMITATIONS: Dysphagia and GERD symptoms were self-reported. CONCLUSIONS: Electrosurgical incision of Schatzki's rings is safe and offers longer symptom-free survival compared with bougie dilation. The addition of rabeprazole offered significant improvement in GERD scores in both groups.

Sublingual L-hyoscyamine for duodenal antimotility during ERCP: a prospective randomized double-blinded study.

BACKGROUND: ERCP is often made difficult by duodenal motility. Glucagon is typically used to inhibit this motility. L-hyoscyamine is an antimuscarinic, anticholinergic agent shown to be a feasible intravenous alternative to glucagon. OBJECTIVE: Demonstrate whether pre-ERCP sublingual L-hyoscyamine reduces the amount of glucagon required to complete ERCP. DESIGN: Randomized, double-blinded clinical trial of 200 participants assigned to receive L-hyoscyamine 0.5 mg or a placebo sublingually before ERCP. Comparative costs were determined. SETTING: Tertiary referral university hospital in the intermountain west. PATIENTS: Mix of inpatients and outpatients. MAIN OUTCOME MEASUREMENTS: The amount of supplemental glucagon required to complete ERCP was recorded, along with procedural outcomes and adverse effects. RESULTS: The 2 groups (101 L-hyoscyamine, 99 placebo) were equally matched in terms of patient and procedure characteristics. There was a decrease in the amount of glucagon required to complete ERCP in the L-hyoscyamine group versus the placebo group, but the reduction was not statistically significant. No differences in complication rates, procedural difficulty, success rates, adverse drug effects, or patient disposition existed between the L-hyoscyamine and placebo groups. LIMITATIONS: Procedures were performed by more than 1 endoscopist, and rescue glucagon was administered at the sole discretion of the endoscopist; this introduced variation in glucagon administered among the participants. CONCLUSIONS: Preprocedure administration of sublingual L-hyoscyamine did not reduce the amount of glucagon required to complete ERCP.