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Purpose: Pancreatic intraductal oncocytic papillary neoplasms (IOPN) are rare precursors to pancreatic ductal adenocarcinoma. We report cross-sectional computed tomography and magnetic resonance imaging (where available) findings of pancreatic IOPNs., Materials and Methods: Consecutive cases of pancreatic IOPNs identified on pathology between 2008 and 2020 at University of Pittsburgh and Johns Hopkins University were included in the study. Cross-sectional imaging of all patients was reviewed by two subspecialty trained abdominal radiologists. Patient demographics, cross-sectional imaging appearances and growth characteristics were evaluated., Results: In this dual-center study, 14 patients with IOPNs were included. Median age was 64 years, and 64% were male. The median size of the lesions was 5.4 cm (range, 1.4-12.3 cm). All patients had either an enhancing mural nodule (93% of patients) and/or thick internal septations (29%). Thin/imperceptible outer wall was seen in 93%. Main duct was involved in 64% of the cases. Only 14% of the cases did not demonstrate abutment of the main duct. Histologic evaluation of surgical specimen showed high-grade dysplasia without invasive carcinoma in 57% and invasive carcinoma in 43% of cases. Lesions with invasive carcinoma were larger (7.1 cm vs 4.3 cm, P = 0.05) and tended to have larger mural nodule (3.7 cm vs 1.8 cm) compared with those without invasive carcinoma., Conclusion: Pancreatic IOPNs are rare cystic premalignant lesions, which among resected cases, are predominantly seen in middle aged men, are often large, have enhancing mural nodules and frequently harbor invasive carcinoma., Competing Interests: Conflicts of Interest and Source of Funding: No grants were received for this study. None of the authors have any conflicts of interest relevant to this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: A.D.S. has received an honorarium from Foundation Medicine Inc. M.N.N. and Y.E.N. own intellectual property related to the PancreaSeq technology and receive royalties from University of Pittsburgh. R.H.H. has the potential to receive royalty payments from Thrive Earlier Detection for the GNAS invention in an arrangement reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time., Methods: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens., Results: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations., Conclusions: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and study aims  N95-filtering facepiece respirators (FFR) use is associated with physiological changes and symptoms due to impaired nasal airflow and increased breathing resistance. We prospectively studied the effect of using an external nasal dilator (END) in gastroenterology laboratory (gastrointestinal lab) staff using N95FFR. Patients and methods  N95FFR qualitative saccharine fit testing was performed on study participants with and without an END. Prospective data collection and comparisons included: 1) survey of perceived symptoms and difficulty of performing one day of gastrointestinal procedures with N95FFR and 1 day of gastrointestinal procedures with END plus N95FFR in random sequence; and 2) vitals and respiratory belt plethysmography in ten gastroenterologists performing simulated colonoscopy while wearing a surgical mask (SM), N95FFR plus SM, END plus N95FFR plus SM for 20 minutes each in random sequence and rapid succession. Results  Twenty-nine of 31 participants passed the N95FFR and the END plus N95FFR fit test. Twenty-two participants (12 physicians; 11 males; mean age 44.1 years, range 31-61) performed 1 day of gastrointestinal procedures with an N95FFR and 1 day of gastrointestinal procedures with an END plus N95FFR. Significantly less difficulty with nasal breathing and severity of symptoms including breathing difficulty, headache, fatigue and frustration, occurred while using an END plus N95FFR. Respiratory plethysmography peak-to-trough measurement showed an increase during the N95FFR stage compared to the END plus N95FFR stage and the SM stage. Conclusions  N95FFR related respiratory changes and symptom development may be mitigated by END use., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Aims: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies., Methods: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence., Results: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%)., Conclusions: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms., (Published by Elsevier Inc.)

Aims: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations., Methods: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival., Results: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis., Conclusion: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.

Introduction: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD)., Methods: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test. Patients with BE who progressed to HGD/EAC after at least 1 year (n = 58) were matched to patients undergoing surveillance without progression (n = 210, median surveillance 7 years). Baseline biopsies with subspecialist diagnoses of ND, indefinite for dysplasia, or LGD were tested in a blinded manner, and the predictive performance of the test was assessed., Results: This risk prediction test stratified patients with BE based on progression risk with the high-risk group at 4.7-fold increased risk for HGD/EAC compared with the low-risk group (95% confidence interval 2.5-8.8, P < 0.0001). Prevalence-adjusted positive predictive value at 5 years was 23%. The high-risk class and male sex provided predictive power that was independent of pathologic diagnosis, age, segment length, and hiatal hernia. Patients with ND BE who scored high risk progressed at a higher rate (26%) than patients with subspecialist-confirmed LGD (21.8%) at 5 years., Discussion: A risk prediction test identifies patients with ND BE who are at high risk for progression to HGD/EAC and may benefit from early endoscopic therapy or increased surveillance.

Silicones are inorganic compounds that have been used for the purpose of shunting ventricular fluid since the mid-20th century [1]. Complications of ventriculoperitoneal shunts have rarely been attributed to silicone allergy, with only a handful of cases reported in literature. The classic presentation of allergy to silicone ventriculoperitoneal shunt, i.e., abdominal pain with recurrent skin breakdown along the shunt tract, is nonspecific and difficult to distinguish clinically from other causes of shunt-related symptoms. It can be diagnosed by detection of antisilicone antibodies and is treated with removal of the shunt and replacement, if needed, with a polyurethane shunt system. We report the first case of suspected silicone allergy presenting as clinical peritonitis without overt colonic perforation.

Goals: We sought to compare the efficacy and safety of endoscopic ultrasound-guided endoscopic resection (ER) and endoscopic band ligation (EBL) for autoamputation of small duodenal carcinoids., Background: The ideal management of small duodenal carcinoid tumors remains unclear., Study: A retrospective review of duodenal carcinoids over a 10-year period (2002 to 2012) was performed at our tertiary-care teaching hospital. All patients with duodenal carcinoids ≤10 mm in size treated with either ER or EBL were included. The main outcome measurements were the efficacy and safety of endotherapy., Results: A total of 37 patients with 39 subcentimeter duodenal carcinoids were identified. In the EBL group, the mean (SD) tumor size was 6.7±2.1 mm compared with 6.7±1.7 mm in the ER group (P=0.943). The mean Ki-67 index was ≤2% in specimens available for histologic analysis in both groups (16/23 EBL and 15/16 ER). The positive deep margin rate in the ER group was 68.8%. Residual carcinoid tumor cells were detected on follow-up biopsies in 1 patient after EBL, and 2 patients after ER. All underwent subsequent successful endotherapy. No adverse events occurred in the EBL group compared with an 18.8% adverse event rate in the ER group (P=0.066)., Conclusions: Endoscopic ultrasound-guided EBL is a safe, effective method for removal of small superficial duodenal carcinoids and seems to be a lower risk alternative to conventional ER with cautery.

Background: Lymphoepithelial cysts (LEC) of the pancreas are rare benign lesions that can be misdiagnosed as pancreatic masses or cystic neoplasms. With widespread use of abdominal cross-sectional imaging, more pancreatic lesions are being discovered, with EUS being used to further evaluate the abnormality., Objective: Our purpose was to describe EUS and cyst aspirate features of LEC of the pancreas., Design: Case series., Setting: Single tertiary referral center., Patients: Nine patients with lymphoepithelial cysts who underwent EUS-FNA., Results: Five male and 4 female patients were identified (mean age 51 years). All lesions were discovered by CT and described as "peripancreatic" in 67% of cases (6/9). EUS examination described a solid-appearing hypoechoic and heterogeneous mass with subtle postacoustic enhancement in 5 of 9 cases. Four lesions were described as purely cystic: 2 were septated, 1 was unilocular, and 1 had internal papillary fronds. Mean cyst size was 5.2 cm (range 1.7-12 cm). Cyst aspirates revealed a thick milky, creamy, or frothy aspirate in 56% of cases (5/9). Cyst cytologic examination revealed squamous material (nucleated/anucleated cells or keratin debris) in all cases. Lymphocytes were seen in 56% of aspirates (5/9). Carcinoembryonic antigen (CEA) levels were obtained in 5 cases (median 6.5 ng/mL [range 2.9-493.4 ng/mL]). Six patients have avoided surgery on the basis of EUS-FNA cytologic results confirming the diagnosis of LEC. Three patients underwent surgical resection: 2 for symptomatic lesions and 1 for concern for a mucinous cystic neoplasm given an elevated aspirate CEA level. Surgical pathologic examination confirmed LEC in each., Limitations: Retrospective single-center study., Conclusions: LEC should be considered whenever a large, well-defined solid or cystic peripheral pancreatic lesion is found. A thick milky, creamy, or frothy aspirate is common. The presence of squamous material and lymphocytes on cytologic examination is diagnostic of LEC. Aspirate CEA level may be elevated and should be considered in conjunction with cytologic results to avoid misdiagnosis as a mucinous cystic neoplasm. Asymptomatic LEC should be managed conservatively.

Systemic sclerosis is a chronic disorder of connective tissue that affects the gastrointestinal tract in more than 80% of patients. Changes in neuromuscular function with progressive fibrosis of smooth muscle within the muscularis propria impair normal motor function, which may secondarily alter transit and nutrient absorption. Esophageal manifestations with gastroesophageal reflux and dysphagia are the most common visceral manifestation of the disease, often requiring more intense acid-suppressive medication. Gastric involvement may lead to gastroparesis, which can be found in up to 50% of patients. Severe small bowel disease can present as chronic intestinal pseudo-obstruction with distended loops of small intestine, bacterial overgrowth, impaired absorption and progressive development of nutritional deficiencies. While not studied as extensively, systemic sclerosis often also affects colorectal function resulting in constipation, diarrhea or fecal incontinence. Nutritional support and prokinetics have been used with some success to manage gastric and small or large bowel involvement in patients with systemic sclerosis. Despite advances in management, significant gastrointestinal manifestations of systemic sclerosis still carry a poor prognosis with a five-year mortality exceeding 50%.

Background: Failure to appropriately evaluate a positive cancer screening test may negate the value of doing that test. The primary aim of this study was to explore the factors associated with undergoing a full colon evaluation for a positive fecal occult blood test (FOBT) in a single Veterans Affairs center., Methods: Medical records of consecutive patients ages > or = 50 years, who had a positive screening FOBT from March 2000 to February 2001, were abstracted. Patient demographics, dates of ordering and doing follow-up test(s), and adherence with scheduled procedures were collected. The primary outcome, full colon evaluation, was defined as having a colonoscopy or double-contrast barium enema plus flexible sigmoidoscopy completed within 12 months., Results: The sample (N = 538) was 98% men (58% Caucasian, 29% African-American, and 13% unknown race). Approximately 77% of the patients were referred to gastroenterology. Ultimately, only 44% underwent full colon evaluation within 12 months. Approximately 20% of the patients failed to attend a scheduled procedure. Referral to gastroenterology and adherence to follow-up appointments were associated with full colon evaluation. There was no association between African-American versus Caucasian race and full colon evaluation., Conclusions: Less than half of the patients with a positive FOBT had a full colon evaluation within 12 months. Multiple failures were identified, including lack of referral for further testing and patient nonadherence. Although the overall performance in evaluating a positive colorectal cancer screening test was poor, no racial disparity was observed.

A three-plate modular, polymer, and planar waveguiding star coupler for large-core polymer fibers is proposed and an 8 x 8 version is demonstrated. The proposed structure can be mass produced by use of injection-molding technology at a significantly low cost. Power measurements indicate that a performance of 1.9-dB power fluctuation among all receiving channels is possible at the expense of tolerating a 3.1-dB excess power loss. Trade-offs among device compactness, overall power efficiency, and channel fluctuation are discussed.