Somatic Mutational Analysis in Endoscopic Ultrasound-Guided Biopsy of Pancreatic Adenocarcinoma: Assessing Yield and Impact.

INTRODUCTION: We sought to determine the yield of somatic mutational analysis from endoscopic ultrasound (EUS)-guided biopsies of pancreatic adenocarcinoma compared with that of surgical resection and to assess the impact of these results on oncologic treatment. METHODS: We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions. RESULTS: Yield of EUS sampling was 89.5%, comparable with the 95.8% yield of surgical resection. More than a quarter in the EUS cohort carried actionable mutations, and of these, more than 1 in 6 had treatment impacted by mutational analysis. DISCUSSION: EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions.

Per-Oral Endoscopic Myotomy for Esophagogastric Junction Outflow Obstruction: A Multicenter Pilot Study.

Esophagogastric junction outflow obstruction (EGJOO) is a rare but increasingly recognized diagnosis as described by The Chicago Classification of Esophageal Motility Disorders version 3.0 (version 3.0).1 On high-resolution manometry (HRM), EGJOO is characterized by increased integrated relaxation pressure (IRP) of the lower esophageal sphincter (LES), yet with some preserved esophageal peristalsis.2-4 Little consensus exists on the preferred therapeutic approach.3 Although conceptually per-oral endoscopic myotomy (POEM) should address the measurable dysfunction in the LES, few data exist to support this.5 Thus, we aimed to evaluate the safety and efficacy of POEM for the treatment of symptomatic EGJOO.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

New onset diabetes predicts progression of low risk pancreatic mucinous cysts.

BACKGROUND: Patients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts. METHODS: We evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method. RESULTS: The 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5-57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%-20.2%), compared to only 0.8% (95%CI, 0.0%-2.3%) for patients without NODM. Among patients with the largest cysts (20-29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%-89.9%) compared to only 7.5% (95%CI, 1.6%-15.2%) for patients without NODM. CONCLUSION: New onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.

Radiomics Boosts Deep Learning Model for IPMN Classification.

Intraductal Papillary Mucinous Neoplasm (IPMN) cysts are pre-malignant pancreas lesions, and they can progress into pancreatic cancer. Therefore, detecting and stratifying their risk level is of ultimate importance for effective treatment planning and disease control. However, this is a highly challenging task because of the diverse and irregular shape, texture, and size of the IPMN cysts as well as the pancreas. In this study, we propose a novel computer-aided diagnosis pipeline for IPMN risk classification from multi-contrast MRI scans. Our proposed analysis framework includes an efficient volumetric self-adapting segmentation strategy for pancreas delineation, followed by a newly designed deep learning-based classification scheme with a radiomics-based predictive approach. We test our proposed decision-fusion model in multi-center data sets of 246 multi-contrast MRI scans and obtain superior performance to the state of the art (SOTA) in this field. Our ablation studies demonstrate the significance of both radiomics and deep learning modules for achieving the new SOTA performance compared to international guidelines and published studies (81.9% vs 61.3% in accuracy). Our findings have important implications for clinical decision-making. In a series of rigorous experiments on multi-center data sets (246 MRI scans from five centers), we achieved unprecedented performance (81.9% accuracy). The code is available upon publication.

New-Onset Diabetes Is a Potential Marker for the Malignant Transformation of Pancreatic Cysts: A Real-World Population Cohort Study.

OBJECTIVES: New-onset diabetes mellitus has been shown to be associated with pancreatic cancer (PC) in the general population. Our objective was to leverage real-world data to assess the association of new-onset diabetes (NODM) with malignant transformation in a large longitudinal cohort of pancreatic cyst patients. METHODS: A retrospective longitudinal cohort study was conducted using IBM's MarketScan claims databases from 2009 to 2017. From 200 million database subjects, we selected patients with newly diagnosed cysts without prior pancreatic pathology. RESULTS: Of the 137,970 patients with a pancreatic cyst, 14,279 had a new diagnosis. Median follow-up was 41.6 months. Patients with NODM progressed to PC at nearly 3 times the rate of patients without a diabetes history (hazard ratio, 2.80; 95% confidence interval, 2.05-3.83) and at a significantly higher rate than patients with preexisting diabetes (hazard ratio, 1.59; 95% confidence interval, 1.14-2.21). The mean interval between NODM and cancer diagnosis was 7.5 months. CONCLUSIONS: Cyst patients who developed NODM progressed to PC at 3 times the rate of nondiabetics and at a greater rate than preexisting diabetics. The diagnosis of NODM preceded cancer detection by several months. These results support the inclusion of diabetes mellitus screening in cyst surveillance algorithms.

Prevalence, Incidence, and Risk of Progression of Asymptomatic Pancreatic Cysts in Large Sample Real-world Data.

OBJECTIVES: Using large-sample, real-world administrative claims data, we evaluated the prevalence of putatively asymptomatic pancreatic cysts, the historical growth in their incident diagnosis, and their risk of malignant progression. METHODS: Data were sourced from IBM MarketScan administrative claims databases of more than 200 million patients. Period prevalence was assessed using 700,000 individuals without conditions that predispose to pancreatic cyst. The standardized cumulative incidence was compared with the cross-sectional abdominal imaging rate from 2010-2017. The risk of progression to pancreatic cancer for 14,279 newly diagnosed patients with a cyst was estimated using Kaplan-Meier analysis. RESULTS: Standardized prevalence increased exponentially with age and was 1.84% (95% confidence interval, 1.80%-1.87%) for patients older than 45. Standardized incidence nearly doubled from 2010-2017 (6.3 to 11.4 per 10,000), whereas the imaging rate changed from only 8.0% to 9.4%. The cumulative risk of pancreatic cancer at 7 years was 3.0% (95% confidence interval, 2.4%-3.5%), increasing linearly (R2 = 0.991) with an annual progression risk of 0.47%. CONCLUSIONS: Using large-sample data, we show a significant burden of asymptomatic pancreatic cysts, with an annual risk of progression to cancer of 0.47% for 7 years. Rapid growth in cyst diagnosis over the last decade far outpaced increases in the imaging rate.

Gastrointestinal endoscopy during the coronavirus pandemic in the New York area: results from a multi-institutional survey.

Background and study aims The coronavirus disease 2019 (COVID-19), and measures taken to mitigate its impact, have profoundly affected the clinical care of gastroenterology patients and the work of endoscopy units. We aimed to describe the clinical care delivered by gastroenterologists and the type of procedures performed during the early to peak period of the pandemic. Methods Endoscopy leaders in the New York region were invited to participate in an electronic survey describing operations and clinical service. Surveys were distributed on April 7, 2020 and responses were collected over the following week. A follow-up survey was distributed on April 20, 2020. Participants were asked to report procedure volumes and patient characteristics, as well protocols for staffing and testing for COVID-19. Results Eleven large academic endoscopy units in the New York City region responded to the survey, representing every major hospital system. COVID patients occupied an average of 54.5 % (18 - 84 %) of hospital beds at the time of survey completion, with 14.5 % (2 %-23 %) of COVID patients requiring intensive care. Endoscopy procedure volume and the number of physicians performing procedures declined by 90 % (66 %-98 %) and 84.5 % (50 %-97 %) respectively following introduction of restricted practice. During this period the most common procedures were EGDs (7.9/unit/week; 88 % for bleeding; the remainder for foreign body and feeding tube placement); ERCPs (5/unit/week; for cholangitis in 67 % and obstructive jaundice in 20 %); Colonoscopies (4/unit/week for bleeding in 77 % or colitis in 23 %) and least common were EUS (3/unit/week for tumor biopsies). Of the sites, 44 % performed pre-procedure COVID testing and the proportion of COVID-positive patients undergoing procedures was 4.6 % in the first 2 weeks and up to 19.6 % in the subsequent 2 weeks. The majority of COVID-positive patients undergoing procedures underwent EGD (30.6 % COVID +) and ERCP (10.2 % COVID +). Conclusions COVID-19 has profoundly impacted the operation of endoscopy units in the New York region. Our data show the impact of a restricted emergency practice on endoscopy volumes and the proportion of expected COVID positive cases during the peak time of the pandemic.

Effect of aerobic exercise on cognition in younger adults: A randomized clinical trial.

OBJECTIVE: To determine efficacy of aerobic exercise for cognitive function in younger healthy adults. METHODS: In a randomized, parallel-group, observer-masked, community-based clinical trial, 132 cognitively normal individuals aged 20-67 with below median aerobic capacity were randomly assigned to one of two 6-month, 4-times-weekly conditions: aerobic exercise and stretching/toning. Efficacy measures included aerobic capacity; cognitive function in several domains (executive function, episodic memory, processing speed, language, and attention), everyday function, body mass index (BMI), and cortical thickness. RESULTS: Aerobic capacity increased significantly (ß = 2.718; p = 0.003), and BMI decreased significantly (ß = -0.596; p = 0.013) in the aerobic exercise but not in the stretching/toning condition. Executive function improved significantly in the aerobic exercise condition; this effect was moderated by age (ß = 0.018 SD/y; p = 0.028). At age 40, the executive function measure increased by 0.228 SD (95% confidence interval [CI] 0.007-0.448), and by 0.596 SD (95% CI 0.219-0.973) at age 60. Cortical thickness increased significantly in the aerobic exercise group in a left frontal region and did not interact with age. Controlling for age and baseline performance, individuals with at least one APOE ε4 allele showed less improvement in executive function with aerobic exercise (ß = 0.5129, 95% CI 0.0381-0.988; p = 0.0346). CONCLUSIONS: This randomized clinical trial demonstrates the efficacy of aerobic exercise for cognition in adults age 20-67. The effect of aerobic exercise on executive function was more pronounced as age increased, suggesting that it may mitigate age-related declines. Increased cortical thickness suggests that aerobic exercise contributes to brain health in individuals as young as age 20. CLINICALTRIALSGOV IDENTIFIER: NCT01179958. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for adults age 20-67 with below median aerobic capacity, aerobic exercise significantly improves executive function but not other measures of cognitive function.