A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Hemosuccus Pancreaticus Following Acute Pancreatitis in a 12-years-old Boy Secondary to Pancreatic Pseudoaneurysm Treated With Endovascular Coil Embolization.

Hemosuccus pancreaticus is a very rare cause of upper gastrointestinal bleeding in children. It is defined as bleeding from the pancreatic or peripancreatic vessels into the main pancreatic duct and may be life-threatening. We present the case of a 12-year-old boy with hematemesis and severe anemia that developed following an episode of acute pancreatitis. Upper endoscopy did not reveal a bleeding source. An endoscopic retrograde cholangiopancreatography performed for the evaluation of common bile duct obstruction identified bleeding from the pancreatic duct. Subsequently, the bleeding source, a pseudoaneurysm of the splenic artery, was identified by conventional angiography and occluded with coil embolization. The diagnosis of hemosuccus pancreaticus may be difficult in children due to rare occurrence and the unusual anatomical site; hence, a high index of suspicion is needed in a patient with a history of pancreatitis who presents with intermittent upper gastrointestinal bleeding and normal upper endoscopy.

A Prospective, Randomized Comparison of Duodenoscope Reprocessing Surveillance Methods.

Duodenoscope use in healthcare facilities has been associated with transmission of multidrug resistant pathogens between patients. To assist healthcare facilities in monitoring the quality of their duodenoscope reprocessing procedures and limit patient risk of infection, the Centers for Disease Control and Prevention (CDC) deployed voluntary interim duodenoscope sampling and culturing surveillance protocols in 2015. Though the interim methods were widely adopted, alternative surveillance protocols were developed and implemented at individual institutions. Here, we compared two sampling methods-the 2015 CDC interim protocol and an alternative protocol developed by the University of Wisconsin Hospitals and Clinics (UWHC). We hypothesized that the UWHC protocol would detect a higher incidence of bacterial contamination from reprocessed duodenoscopes. A total of 248 sampling events were performed at UWHC. The CDC protocol (n = 129 sampling events) required culturing samples collected from each duodenoscope after brushing its terminal end and flushing its lumen with sterile water. The UWHC protocol (n = 119 sampling events) required culturing samples collected from each duodenoscope after swabbing its elevator, immersing its terminal end into broth and flushing its lumen with saline. With the CDC method, 8.53% (n = 11) of the duodenoscopes sampled were positive for bacterial growth with 15 isolates recovered. Using the UWHC method, 15.13% (n = 18) of cultures were positive for bacterial growth with 20 isolates recovered. The relative risk of identifying a contaminated duodenoscope using the CDC interim method, however, was not different than when using the UWHC protocol. Mean processing time (27.35 and 5.11 minutes, p < 0.001) and total cost per sample event ($17.87 and $15.04) were lower using the UWHC method. As the UWHC protocol provides similar detection rates as the CDC protocol, the UWHC method is useful, provided the shorter processing time and lower cost to perform.

A tertiary care hospital's 10 years' experience with rectal ultrasound in early rectal cancer.

BACKGROUND AND OBJECTIVES: Rectal endoscopic ultrasound (RUS) has become an essential tool in the management of rectal adenocarcinoma because of the ability to accurately stage lesions. The aim of this study was to identify the staging agreement of early RUS-staged rectal adenocarcinoma with surgical resected pathology and ultimately determine how this impacts the management of early rectal cancer (T1-T2). METHODS: Retrospective chart review was performed from November 2002 to November 2013 to identify procedure indication, RUS staging data, surgical management, and postoperative surgical pathology data. RESULTS: There were a total of 693 RUS examinations available for review and 282 of these were performed for a new diagnosis of rectal adenocarcinoma. There was staging agreement between RUS and surgical pathology in 19 out of 20 (95%) RUS-staged T1 cases. There was staging agreement between RUS and surgical pathology in 3 out of 9 (33%) RUS-staged T2 cases. There was significantly better staging agreement for RUS-staged T1 lesions compared to RUS staged T2 lesions (P = 0.002). Nearly 60% of T1N0 cancers were referred for transanal excisions (TAEs), and 78% of T2N0 cancers underwent low anterior resection. CONCLUSIONS: This study identified only a small number of T1-T2 adenocarcinomas. There was good staging agreement between RUS and surgical pathology among RUS-staged T1 lesions whereas poor staging agreement among RUS-staged T2 lesions. Although TAE is largely indicated by the staging of a T1 lesion, this approach may be less appropriate for T2 lesions due to high reported local recurrence.

Primary Care Provider Perceptions of Colorectal Cancer Screening Barriers: Implications for Designing Quality Improvement Interventions.

Aims. Colorectal cancer (CRC) screening is underutilized. Increasing CRC screening rates requires interventions targeting multiple barriers at each level of the healthcare organization (patient, provider, and system). We examined groups of primary care providers (PCPs) based on perceptions of screening barriers and the relationship to CRC screening rates to inform approaches for conducting barrier assessments prior to designing and implementing quality improvement interventions. Methods. We conducted a retrospective cohort study linking EHR and survey data. PCPs with complete survey responses for questions addressing CRC screening barriers were included (N = 166 PCPs; 39,430 patients eligible for CRC screening). Cluster analysis identified groups of PCPs. Multivariate logistic regression estimated odds ratios and 95% confidence intervals for predictors of membership in one of the PCP groups. Results. We found two distinct groups: (1) PCPs identifying multiple barriers to CRC screening at patient, provider, and system levels (N = 75) and (2) PCPs identifying no major barriers to screening (N = 91). PCPs in the top half of CRC screening performance were more likely to identify multiple barriers than the bottom performers (OR, 4.14; 95% CI, 2.43-7.08). Conclusions. High-performing PCPs can more effectively identify CRC screening barriers. Targeting high-performers when conducting a barrier assessment is a novel approach to assist in designing quality improvement interventions for CRC screening.

Low Yield and High Cost of Gastric and Duodenal Biopsies for Investigation of Symptoms of Abdominal Pain During Routine Esophagogastroduodenoscopy.

BACKGROUND: Esophagogastroduodenoscopy (EGD) referrals for symptoms of abdominal pain are common. Current guidelines for dyspepsia recommend biopsies of gastric mucosa for Helicobacter pylori in all patients referred for EGD. Our study aimed to determine the clinical yield and cost-effectiveness of gastric and duodenal biopsy in EGDs performed for abdominal pain. METHODS: Three hundred and ninety-one outpatient EGDs performed at a single academic tertiary care center were studied. For each procedure, endoscopic as well as pathologic findings from the stomach and duodenum were then recorded. Charge of biopsy was calculated using the increased charges for professional fees, forceps, and pathology fees when a biopsy was performed. RESULTS: Gastric biopsies were obtained on 304 EGDs performed with 13 (4.2%) patients diagnosed with H. pylori. In patients with abnormal gastric mucosa on EGD, 11 of 167 (6.5%) were positive for H. pylori compared to 2 of 137 (1.4%) with normal appearing mucosa (p = 0.02). Charge per diagnosis of H. pylori for normal mucosa was calculated to be $43,073. Duodenal biopsies were performed in 263 cases. Celiac disease was diagnosed in 4 of 263 cases (1.5%). Of patients with abnormal duodenal mucosa on EGD, 1 of 36 (2.7%) were positive for celiac disease compared to 3 of 227 (1.3%) with normal mucosa (p = 0.57). Charge per diagnosis of celiac disease for normal mucosa was calculated to be $47,580. CONCLUSION: Routine biopsy during EGD for symptoms of abdominal pain has low yield with high costs. Practice of routine biopsies of normal appearing tissue and the present guidelines should be reconsidered in the investigation of abdominal pain with EGD.

Predictors of primary care provider adoption of CT colonography for colorectal cancer screening.

PURPOSE: To examine factors influencing primary care provider (PCP) adoption of CT colonography (CTC) for colorectal cancer (CRC) screening. MATERIALS AND METHODS: We performed a retrospective cohort study linking electronic health record (EHR) data with PCP survey data. Patients were eligible for inclusion if they were not up-to-date with CRC screening and if they had CTC insurance coverage in the year prior to survey administration. PCPs were included if they had at least one eligible patient in their panel and completed the survey (final sample N = 95 PCPs; N = 6245 patients). Survey data included perceptions of CRC screening by any method, as well as CTC specifically. Multivariate logistic regression estimated odds ratios and 95% confidence intervals for PCP and clinic predictors of CRC screening by any method and screening with CTC. RESULTS: Substantial variation in CTC use was seen among PCPs and clinics (range 0-16% of CRC screening). Predictors of higher CTC use were PCP perceptions that CTC is effective in reducing CRC mortality, higher number of perceived advantages to screening with CTC, and Internal Medicine specialty. Factors not associated with CTC use were PCP perceptions of less organizational capacity to meet demand for colonoscopy, number of perceived disadvantages to screening with CTC, PCP age and gender, and clinic factors. CONCLUSION: Significant variation in PCP adoption of CTC exists. PCP perceptions of CTC and specialty practice were related to CTC adoption. Strategies to increase PCP adoption of CTC for CRC screening should include emphasis on the effectiveness and advantages of CTC.

Impact and outcomes of research sponsored by the American Society for Gastrointestinal Endoscopy.

BACKGROUND AND AIMS: Since 1985, the American Society for Gastrointestinal Endoscopy (ASGE) has awarded grants for endoscopic-related research. The goals of this study were to examine trends in ASGE grant funding and to assess productivity of previous recipients of the ASGE grant awards. METHODS: This was a retrospective cohort analysis of all research grants awarded by the ASGE through 2009. Measures of academic productivity and self-assessment of the ASGE awards' impact on the recipients' careers were defined by using publicly available resources (eg, National Library of Medicine-PubMed) and administration of an electronic survey to award recipients. RESULTS: The ASGE awarded 304 grants totaling $12.5 million to 214 unique awardees. Funding increased 7.5-fold between 1985 and 1989 (mean $102,000/year) and between 2005 and 2009 (mean $771,000/year). The majority of awardees were men (83%), were at or below the level of assistant professor (82%), with a median of 3 years of postfellowship experience at the time of the award, and derived from a broad spectrum of institutions as measured by National Institutes of Health funding rank (median 26, interquartile range [IQR] 12-64). Nineteen percent had a master's degree in a research-related field. Awardees' median publications per year increased from 3.5 (IQR 1.2-9.0) before funding to 5.7 (IQR 1.8-9.5) since funding; P = .04, and median h-index scores increased from 3 (IQR 1-8) to 17 (IQR 8-26); P < .001. Multivariate analysis found that the presence of a second advanced degree (eg, masters or doctorate) was independently predictive of high productivity (odds ratio [OR] 2.92; 95% confidence interval [CI], 1.09-7.81). Among 212 unique grant recipients, 82 (40%) completed the online survey. Of the respondents, median peer-reviewed publications per year increased from 3.4 (IQR 1.9-5.5) to 4.5 (IQR 2.0-9.5); P = .17. Ninety-one percent reported that the ASGE grant had a positive or very positive impact on their careers, and 85% of respondents are currently practicing in an academic environment. Most of the grants resulted in at least 1 peer-reviewed publication (67% per Internet-based search and 81% per survey). CONCLUSIONS: The ASGE research program has grown considerably since 1985, with the majority of grants resulting in at least 1 grant-related publication. Overall academic productivity increased after the award, and the majority of awardees report a positive or very positive impact of the award on their careers. Medical professional societies are an important sponsor of clinical research.

High Definition Colonoscopy Combined with i-SCAN Imaging Technology Is Superior in the Detection of Adenomas and Advanced Lesions Compared to High Definition Colonoscopy Alone.

Background. Improved detection of adenomatous polyps using i-SCAN has mixed results in small studies. Utility of i-SCAN as a primary surveillance modality for colorectal cancer screening during colonoscopy is uncertain. Aim. Comparing high definition white light endoscopy (HDWLE) to i-SCAN in their ability to detect adenomas during colonoscopy. Methods. Prospective cohort study of 1936 average risk patients who had a screening colonoscopy at an ambulatory procedure center. Patients underwent colonoscopy with high definition white light endoscopy withdrawal versus i-SCAN withdrawal during endoscopic screening exam. Primary outcome measurement was adenoma detection rate for i-SCAN versus high definition white light endoscopy. Secondary measurements included polyp size, pathology, and morphology. Results. 1007 patients underwent colonoscopy with i-SCAN and 929 with HDWLE. 618 adenomas were detected in the i-SCAN group compared to 402 in the HDWLE group (p < 0.01). More advanced adenomas (≥10 mm) were found by i-SCAN, 79 versus 47 (p = 0.021) and based upon histology alone 37 versus 18 (p = 0.028). Conclusions. i-SCAN detected significantly more adenomas and advanced adenomas compared to high definition white light endoscopy.

Variation in Aptitude of Trainees in Endoscopic Ultrasonography, Based on Cumulative Sum Analysis.

BACKGROUND & AIMS: Studies have reported substantial variation in the competency of advanced endoscopy trainees, indicating a need for more supervised training in endoscopic ultrasound (EUS). We used a standardized, validated, data collection tool to evaluate learning curves and measure competency in EUS among trainees at multiple centers. METHODS: In a prospective study performed at 15 centers, 17 trainees with no prior EUS experience were evaluated by experienced attending endosonographers at the 25th and then every 10th upper EUS examination, over a 12-month training period. A standardized data collection form was used (using a 5-point scoring system) to grade the EUS examination. Cumulative sum analysis was applied to produce a learning curve for each trainee; it tracked the overall performance based on median scores at different stations and also at each station. Competency was defined by a median score of 1, with acceptable and unacceptable failure rates of 10% and 20%, respectively. RESULTS: Twelve trainees were included in the final analysis. Each of the trainees performed 265 to 540 EUS examinations (total, 4257 examinations). There was a large amount of variation in their learning curves: 2 trainees crossed the threshold for acceptable performance (at cases 225 and 245), 2 trainees had a trend toward acceptable performance (after 289 and 355 cases) but required continued observation, and 8 trainees needed additional training and observation. Similar results were observed at individual stations. CONCLUSIONS: A specific case load does not ensure competency in EUS; 225 cases should be considered the minimum caseload for training because we found that no trainee achieved competency before this point. Ongoing training should be provided for trainees until competency is confirmed using objective measures.

Visual evaluation of the larynx and hypopharynx during esophagogastroduodenoscopy: a safety and feasibility study.

BACKGROUND: The larynx and hypopharynx are common sites for head and neck cancer, which shares many risk factors with upper digestive tract disease. Patient survival with malignancies depends on stage at the time of diagnosis. Endoscopic screening of the hypopharynx is neither routinely performed in clinical practice nor has it been evaluated in a formal study. METHODS: This is a prospective pilot study of patients undergoing routine EGD. Demographic data were collected from patients prior to the procedure. All patients in the study underwent an EGD and prior to performing the standard portion of the EGD procedure, the endoscopist evaluated the larynx and hypopharynx with both white light endoscopy (WLE) and narrow band imaging (NBI). Details of the procedure, including ability to see all anatomic structures, time spent, complications, and findings, were recorded. RESULTS: A total of 111 patients were included in the study. The exam of the laryngopharynx was completed in 87% of patients (97/111). Reasons for incomplete exam included intubated patients (2/14), inadequate sedation (9/14), and inability to see the entire hypopharynx (3/14). The mean time of the WLE was 20.2 s, while the NBI evaluation took 15.6 s for a mean and 35.8 s for the entire exam of the larynx and hypopharynx. Minor procedural complications occurred in 3/11 (2.7%) of the patients and included hypotension, tachycardia, and hypoxia. There were 6 patients who had hypopharyngeal abnormalities seen on both WLE and NBI (5.4%) and were subsequently referred to otolaryngology. Of the six referrals, one patient had a vocal cord biopsy showing leukoplakia, while the others were deemed normal anatomic variants. CONCLUSIONS: Evaluation of the hypopharynx can be accomplished by gastrointestinal endoscopists at the time of EGD in the vast majority of patients in a safe manner while adding only about 35 s to the overall exam time.

Differentiating primary pancreatic lymphoma from adenocarcinoma using endoscopic ultrasound characteristics and flow cytometry: A case-control study.

BACKGROUND: Primary pancreatic lymphoma (PPL) is a rare pancreatic neoplasm that is difficult to diagnose. PPL has a vastly different prognosis and treatment regimen than other pancreatic tumors; therefore, accurate diagnosis is vital. In this article, we describe the characteristic presentation, endoscopic ultrasound (EUS) features, and the role of fine-needle aspiration (FNA) in the diagnosis of PPL compared with pancreatic adenocarcinoma. MATERIALS AND METHODS: This was a retrospective case-control study of 11 patients diagnosed with PPL via EUS between 2002 and 2011. The clinical and EUS features of the cases were then compared with age-matched controls with adenocarcinoma in a 1:3 ratio. RESULTS: There were 11 patients with PPL and 33 with adenocarcinoma. At last follow-up, 7 of 11 PPL patients were alive, and 3 of 33-adenocarcinoma patients were alive (P < 0.001). The most common presenting symptoms for PPL were pain 73%, weight loss 45%, and jaundice 18%, while patients with adenocarcinoma presented with pain 52% (P = 0.3), weight loss 30% (P = 0.47) and jaundice 76% (P = 0.001). The EUS appearance was similar in the two groups in that ultrasound imaging of the pancreas lesions tended to be hypoechoic and heterogenous, but the PPL group was more likely to have peripancreatic lymphadenopathy (LAD) (64% vs. 18%, P = 0.008) and were larger (4.8 cm × 5.3 cm vs. 3.2 cm × 3.1 cm, P < 0.001). The PPL group was less likely to have vascular invasion (18% vs. 55%, P = 0.045) and less likely to be found in the head of the pancreas (36% vs. 85%, P = 0.004). FNA and cytology (without flow cytometry [FC]) made the diagnosis in 28% of PPL patients compared with 91% of adenocarcinoma patients (P = 0.002). In the PPL group, 7 of 11 FNA samples were sent for FC. If FC was added, then the diagnosis of PPL was increased to 100%. CONCLUSIONS: Compared with adenocarcinoma, pancreatic lymphoma has a better prognosis, is less likely to present with jaundice and less likely to have vascular invasion. PPL is more likely to be located outside the head of the pancreas and to include peripancreatic LAD, and is less likely to be diagnosed with cytology. The diagnostic accuracy of FNA for PPL is improved greatly with the addition of FC.

Wireless capsule endoscopy.

Over the last decade, WCE has established itself as a valuable test for imaging the small intestine. It is a safe and relatively easy procedure to perform that can provide valuable information in the diagnosis of small-bowel conditions. Its applications still remain limited within the esophagus and colon. Future developments may include improving visualization within the esophagus and developing technologies that may allow manipulation of the capsule within the GI tract and biopsy capabilities.

Predictors of colorectal cancer screening variation among primary-care providers and clinics.

OBJECTIVES: Colorectal cancer (CRC) screening is underutilized. To effect change, we must understand reasons for underuse at multiple levels of the health-care system. We evaluated patient, provider, and clinic factors that predict variation in CRC screening among primary-care clinics and primary-care providers (PCPs). METHODS: We analyzed electronic medical record (EMR) data for 34,319 adults eligible for CRC screening, 19 clinics, and 97 PCPs in a large, academic physician group. Detailed data on potential patient, provider, and clinic predictors of CRC screening were obtained from the EMR. PCP perceptions of CRC screening barriers were measured via survey. The outcome was completion of CRC screening at the patient level. Multivariate logistic regression with clustering on clinics obtained adjusted odds ratios and 95% confidence intervals for potential predictors of CRC screening at each level. RESULTS: Seventy-one percentage of patients completed CRC screening. Variation in screening rates was seen among clinics (51-80%) and among PCPs (51-82%). Significant predictors of completing CRC screening were identified at all levels: patient (older age, white race, being married, primarily English-speaking, having commercial insurance plans vs. Medicare or Medicaid, and higher health-care resource utilization), provider (larger panel size of patients eligible for CRC screening), and clinic (hospital-owned, shorter distance to nearest optical colonoscopy center). CONCLUSIONS: Variation in CRC screening exists among primary-care clinics and providers within a single clinic. Predictors of variation can be identified at patient, provider, and clinic levels. Quality improvement interventions addressing CRC screening need to be directed at multiple levels of the health-care system.