Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool.

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF) of commonly altered genes (BRAF, CDKN2A, CTNNB1, GNAS, RAS, PIK3CA, PTEN, SMAD4, TP53 and VHL) was evaluated for their ability to identify and grade mucinous PCL. Results: Cytology showed a diagnostic sensitivity of 43.5% for mucinous PCL due in part to the impact of non-diagnostic (28.8%) and negative (50.5%) specimens. Incorporating an algorithmic approach or molecular analysis markedly increased the accuracy of cytologic evaluation. Detection of mucinous PCL by molecular analysis was 93.3% based on the detection of KRAS and/or GNAS gene mutations (p = 0.0001). Additional genes provided a marginal improvement in sensitivity but were associated with cyst type (e.g. VHL) and grade (e.g. SMAD4). In the surgical cohort, molecular analysis and the proposed algorithm showed comparable sensitivity (88.9% vs. 100%). Conclusions: Incorporating somatic molecular analysis in the cytologic evaluation of EUS-FNA increases diagnostic accuracy for detection, classification and grading of PCL. This approach has the potential to improve patient management.

Systematic Analysis and Critical Appraisal of the Quality of the Scientific Evidence and Conflicts of Interest in Practice Guidelines (2005-2013) for Barrett's Esophagus.

BACKGROUND: Barrett's esophagus (BE) is a condition that has a small but important risk of progressing to esophageal cancer. To date, no study has assessed the strength of evidence supporting the recommendations for BE. We sought to assess the overall quality of the recommendations and strength of the BE using the AGREE II instrument. METHODS: A PubMed search was performed to identify guidelines published pertaining to BE. Every guideline was reviewed using the AGREE II format to assess the methodological rigor and validity of the guideline. Additionally, guidelines were reviewed for the level of evidence used to support recommendations, conflicts of interest (COI), and differences in recommendations. Statistical analysis was performed using Stata (version 12). RESULTS: In total, 234 manuscripts were identified of which 8 guidelines published between 2005 and 2013 pertained to BE. Seventy-five percentage (6/8) graded the evidence used to formulate recommendations. Of the 126 recommendations with supporting evidence, 6 % were supported by level A evidence, 49 % level B evidence, and 45 % level C evidence. Using the AGREE II format, the highest overall assessment grade was the BSG BE guideline (6.5 ± 0.6) followed by the AGA (5.5 ± 0.6). The highest rated domains were scope and purpose (mean 77 range 24-96) and clarity of presentation (mean 75), while the lowest rated domains were editorial independence (mean 32 range 0-92) and applicability of the guideline (mean 35 range 7-90). There was significant variability in recommendations regarding who to screen for BE and surveillance intervals. Finally, only 50 % of the guidelines disclosed if COI were present and 75 % (3/4) reported potentially relevant COI. CONCLUSIONS: Majority of the BE guideline fail to meet the AGREE II domains, and most of the recommendations are level B or C quality evidence. Further interventions are necessary to improve the overall quality of the guidelines.

Tamoxifen-associated portal vein thrombosis causing severe oesophageal variceal bleeding.

A 46-year-old woman with medical history of breast cancer on tamoxifen presented with syncope. On arrival to the hospital, the patient developed massive haematemesis and a subsequent esophagogastroduodenoscopy revealed oesophageal varices without any known history of liver disease. Further evaluation identified portal vein thrombosis probably caused by tamoxifen use.

Multicenter Study Assessing Physician Recommendations Regarding the Continuation of Aspirin and/or NSAIDs Prior to Gastrointestinal Endoscopy.

BACKGROUND: In 2009 the American Society for Gastrointestinal Endoscopy (ASGE) guidelines advised that both aspirin and NSAIDs be continued prior to low-risk gastrointestinal endoscopic procedures. We sought to determine physician knowledge regarding these guidelines. METHODS: A survey questionnaire was developed based on the ASGE guidelines. Physicians were queried about whether they would continue/stop aspirin in a patient with cardiac disease and in a patient taking NSAIDs for arthritis whether they would continue/stop NSAIDs prior to endoscopy. The survey was administered at three academic medical centers. Demographic information: level of training, board certification, teaching trainees, percentage of time in clinical practice, year of medical school graduation, and location of medical school were all reviewed. The primary outcome was number of questions answered correctly and predictors of correct responses. RESULTS: The survey was administered to 941 participants with 12 declining to participate, while 80% (740/929) of the subjects completed the survey; 20% (150/740) respondents answered both questions correctly and 42% (310/740) answered one question correctly. There was no significant difference between institutions (p = 0.6) or between attendings and trainees (p = 0.75). Multivariate predictors of correct answers were self-reported familiarity with the guideline (-0.029; 95% CI -0.003 to -0.056, p < 0.031), level of training (0.050; 95% CI 0.012-0.088, p = 0.010), and specialty (0.108; 95% CI 0.058-0.159, p < 0.0001). Finally, there was an inverse, linear relationship between postgraduate year and percent questions correct. CONCLUSION: Physician knowledge of guidelines regarding the use of aspirin and NSAIDs prior to endoscopy is suboptimal. Interventions are necessary to improve knowledge of the current pre-procedure guidelines.

Surgery for Ulcerative Colitis Is Associated with a High Rate of Readmissions at 30 Days.

BACKGROUND: Currently, the predictors of readmission after colectomy specifically for ulcerative colitis (UC) are poorly investigated. We sought to determine the rates and predictors of 30-day readmissions after colectomy for UC. METHODS: Patients undergoing total proctocolectomy and end ileostomy, abdominal colectomy with end ileostomy, proctocolectomy with ileoanal pouch anastomosis (IPAA) formation and diverting ileostomy, one stage IPAA, or abdominal colectomy with ileorectal anastomosis at a tertiary care center between January 2002 and January 2012 for UC were included. Patients were identified using ICD-9 code 556.x. Each record was manually reviewed. The electronic record system was reviewed for demographic information, medical histories, UC history, medications, and data regarding the admission and discharge. Charts were reviewed for readmissions within 30 days of surgery. Univariate and multivariate analyses were performed using Stata v.13. RESULTS: Two hundred nine patients with UC underwent a colectomy. Forty-three percent had a proctocolectomy with IPAA and diverting ileostomy and 32% had abdominal colectomy with end ileostomy. Seventy-six percent of surgeries were due to failure of medical therapy and 68% of patients were electively admitted for surgery. Thirty-two percent (n = 67/209) of the cohort was unexpectedly readmitted within 30 days. In multivariate model, proctocolectomy with IPAA and diverting ileostomy (odds ratio [OR] = 2.11; 95% CI, 1.06-4.19; P = 0.033) was the only significant predictor of readmission. Hospital length of stay >7 days (OR = 1.82; 95% CI, 0.98-3.41; P = 0.060), presence of limited UC (OR = 2.10; 95% CI, 0.93-4.74; P = 0.074), and steroid before admission (OR = 1.69; 95% CI, 0.90-3.2; P = 0.100) trended toward significance. CONCLUSIONS: Surgery for UC is associated with a high rate of readmission. Further prospective studies are necessary to determine the means to reduce these readmissions.

Current knowledge of antibiotic prophylaxis guidelines regarding GI open-access endoscopic procedures is inadequate.

BACKGROUND: The American Heart Association (AHA) guidelines from 2007 and the American Society for Gastrointestinal Endoscopy (ASGE) guidelines from 2008 recommended against antibiotic prophylaxis before GI endoscopic procedures to prevent bacterial endocarditis. OBJECTIVE: To determine physician knowledge regarding these guidelines and to identify physician subgroups for which knowledge was suboptimal. DESIGN: A survey questionnaire was developed based on AHA and ASGE guidelines regarding antibiotics before endoscopy. Physicians were queried about 10 theoretical scenarios as to whether or not they would recommend before-procedure antibiotics. SETTING: The survey was administered at 3 academic medical centers. PARTICIPANTS: Attending physicians and trainees in primary care and subspecialties. INTERVENTIONS: Survey. MAIN OUTCOME MEASUREMENTS: Percentage of the survey questions answered correctly and predictors of correct response. RESULTS: The survey was administered to 941 participants of whom 12 declined to participate. Eighty percent (n=740/929) of participants completed the survey. The median number of correct answers was 70% (interquartile range [IQR] 50%-90%) and was similar at each institution (P=.6). A total of 7.3% (n=54) of respondents answered all questions correctly. There was no significant difference in correct responses between attending physicians and trainees or between study centers (median 7, IQR 5-9; P=.75). Gastroenterologists were more likely to answer questions correctly than other subspecialists or primary care physicians (P<.0001). On multivariate analysis, physician knowledge correlated directly with self-reported familiarity with guidelines (0.21; 95% confidence interval [CI], 0.08-0.34; P=.002) and specialty (0.56; 95% CI, 0.30-0.82; P<.001) and inversely with year of medical school graduation (0.22; 95% CI, 0.07-0.37; P=.005). LIMITATIONS: Survey study that used theoretical scenarios. CONCLUSION: Physician knowledge of guidelines regarding antibiotic use before endoscopy is suboptimal. Further interventions are needed to improve the knowledge of before-procedure guidelines.