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.

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.

Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.

BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor SPINK1 further increase the risk of pancreatitis in these patients. METHODS: We screened patients and controls for variants in SPINK1 associated with risk of chronic pancreatitis and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, 150 unrelated controls, 375 additional controls for limited genotyping. CFTR wild-type and p.R75Q were cloned and expressed in HEK293 cells, and relative conductances of HCO(3)(-) and Cl(-) were measured. RESULTS: SPINK1 variants were identified in 36% of subjects and 3% of controls (odds ratio [OR], 18.1). One variant of CFTR not associated with CF, p.R75Q, was found in 16% of subjects and 5.3% of controls (OR, 3.4). Coinheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.38% of controls (OR, 25.1). Patch-clamp recordings of cells that expressed CFTR p.R75Q showed normal chloride currents but significantly reduced bicarbonate currents (P = .0001). CONCLUSIONS: The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk of pancreatitis. Coinheritance of p.R75Q or CF causing CFTR variants with SPINK1 variants significantly increases the risk of ICP.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.

OBJECTIVE: To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS: This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS: Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS: This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.

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.

Smoking is underrecognized as a risk factor for chronic pancreatitis.

BACKGROUND/AIMS: Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor. METHODS: We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject's self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor. RESULTS: Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor. CONCLUSIONS: Physicians often underrecognize smoking as a CP risk factor. Efforts are needed to raise awareness of the association between smoking and CP. and IAP.

Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2).

BACKGROUND: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are complex syndromes associated with numerous etiologies, clinical variables and complications. We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP. METHODS: Between August 2000 and September 2006, a consortium of 20 expert academic and private sites prospectively ascertained 1,000 human subjects with RAP or CP, plus 695 controls (spouse, family, friend or unrelated). Standardized questionnaires were completed by both the physicians and study subjects and blood was drawn for genomic DNA and biomarker studies. All data were double-entered into a database and systematically reviewed to minimize errors and include missing data. RESULTS: A total of 1,000 subjects (460 RAP, 540 CP) and 695 controls who completed consent forms and questionnaires and donated blood samples comprised the final dataset. Data were organized according to diagnosis, supporting documentation, etiological classification, clinical signs and symptoms (including pain patterns and duration, and quality of life), past medical history, family history, environmental exposures (including alcohol and tobacco use), medication use and therapeutic interventions. Upon achieving the target enrollment, data were organized and classified to facilitate future analysis. The approaches, rationale and datasets are described, along with final demographic results. CONCLUSION: The NAPS2 consortium has successfully completed a prospective ascertainment of 1,000 subjects with RAP and CP from the USA. These data will be useful in elucidating the environmental, metabolic and genetic conditions, and to investigate the complex interactions that underlie RAP and CP.

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.

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.

Endoscopic approaches to enteral nutritional support.

Enteral is preferred to parenteral nutritional support for acute and chronic diseases because it is more physiological and associated with fewer infection complications. Nasal tube feedings are generally used for 30 days or less and percutaneous access for the longer-term. Feeding by naso-gastric tubes is appropriate for most critically ill patients. However, trans-pyloric feeding is indicated for those with regurgitation and aspiration of gastric feeds. Deep naso-jejunal tube feeding is appropriate for patients with severe acute pancreatitis. There are several methods for endoscopic placement of naso-enteric tubes. Percutaneous endoscopic gastrostomy is used for most persons requiring long-term support. Long-term jejunal feeding is most often used for persons with chronic aspiration of gastric feeds, chronic pancreatitis intolerant to eating, or persons in need of concomitant gastric decompression. Percutaneous endoscopic gastrostomy with a jejunal tube extension is fraught with tube dysfunction and dislocation. Direct percutaneous endoscopic jejunostomy tubes may be more robust, but are less commonly performed.

Secondary prevention: screening and surveillance of persons at average and high risk for colorectal cancer.

Secondary prevention of colorectal cancer with FOBT and endoscopy with polypectomy decreases cancer deaths. Other available modalities include genetic tests and imaging studies, but outcomes data are not yet available. Issues remain concerning the most appropriate test, the optimal intervals, and cost-efficacy. Patients may be stratified by personal and family risk, and specific strategies may be used. Newer developments in genetic tests and imaging, including virtual colonoscopy, hold promise for the future. The most important issue at present is to have people screened or surveilled by any of the recommended modalities.

Pancreatic carcinoma surveillance in patients with familial melanoma.

OBJECTIVE: To determine the optimal methods for pancreatic adenocarcinoma surveillance in high-risk patients with familial melanoma and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. DESIGN: Case report with pedigree analysis and literature review, with an emphasis on guideline development for high-risk kindreds with familial pancreatic adenocarcinoma. SETTING: A university-affiliated familial melanoma research clinic. Patients The proband was referred as a participant in a research clinic protocol and was found to carry a germline CDKN2A mutation and have a history of melanoma and pancreatic adenocarcinoma. A total of 179 family members were identified through the Utah Population Database and underwent evaluation for history of melanoma and pancreatic adenocarcinoma.Intervention/ METHODS: Comprehensive family history and pedigree analysis performed by means of personal interview, medical record review, and use of cancer registry and population database records. Mutation status was confirmed by results of DNA sequence analysis. Tumor identity was confirmed with immunohistochemical markers. MAIN OUTCOME MEASURES: Estimated risk for pancreatic adenocarcinoma in a high-risk family with CDKN2A-positive melanoma. Guidelines for surveillance in these families were based on review of the literature. RESULTS: Sequence analysis confirmed a CDKN2A mutation, and immunohistochemical evaluation confirmed the diagnoses of metastatic melanoma and metastatic pancreatic adenocarcinoma. Pedigree analysis showed an observed-expected ratio of 8.9 to 12.6 for pancreatic adenocarcinoma and 16.4 to 20.8 for melanoma in this family. Guidelines used for surveillance of kindreds at high risk for pancreatic adenocarcinoma were applied to families with CDKN2A melanoma. Conclusion Patients with melanoma and a germline CDKN2A mutation should be considered for pancreatic adenocarcinoma surveillance that is based on the most recent published studies.

Colorectal cancer: screening and surveillance for high-risk individuals.

Colorectal cancer is very common and is closely related to patient age. After age, the second most common risk factor is family history of colon cancer. In fact, it is one of the most hereditable cancers. Colon cancer is preventable and screening has demonstrated efficacy in the reduction of both the incidence and the mortality from colorectal cancer. Several screening techniques are currently available, including endoscopy and nonendoscopic-based techniques. Screening strategies vary according to the individual risk of colon cancer. This paper will focus on the screening recommendations for patients with high-risk colon cancer.