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Upper gastrointestinal cancers are among the leading causes of cancer deaths worldwide with exceptionally poor prognosis, which is largely attributable to frequently delayed diagnosis. Although effective screening is critical for early detection, the highly variable incidence of upper gastrointestinal cancers presents challenges, rendering universal screening programs suboptimal in most populations globally. Optimal strategies in regions of modest incidence, such as the United States, require a targeted approach, focused on high-risk individuals based on demographic, familial, and clinicopathologic risk factors. Assessment of underlying precancerous lesions has key implications for risk stratification and informing clinical decisions to improve patient outcomes., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC with patients with average onset colorectal cancer (AO-CRC) to help define surveillance outcomes in these groups., Methods: Single-institution retrospective chart review identified EO-CRC and AO-CRC patients with colonoscopy and no evidence of disease. Surveillance intervals and time to development of advanced neoplasia (CRC and advanced polyps [adenoma/sessile serrated]) were examined. For each group, 3 serial surveillance colonoscopies were evaluated. Statistical analyses were performed utilizing log-ranked Kaplan-Meier method and Cox proportional hazards., Results: A total of 1259 patients with CRC were identified, with 612 and 647 patients in the EO-CRC and AO-CRC groups, respectively. Compared with patients with AO-CRC, patients with EO-CRC had a 29% decreased risk of developing advanced neoplasia from time of initial surgery to first surveillance colonoscopy (hazard ratio, 0.71; 95% confidence interval, 0.52-1.0). Average follow-up time from surgical resection to first surveillance colonoscopy was 12.6 months for both cohorts. Overall surveillance findings differed between cohorts (P = .003), and patients with EO-CRC were found to have less advanced neoplasia compared with their counterparts with AO-CRC (12.4% vs 16.0%, respectively). Subsequent colonoscopies found that, while patients with EO-CRC returned for follow-up surveillance colonoscopy earlier than patients with AO-CRC, the EO-CRC cohort did not have more advanced neoplasia nor non-advanced adenomas., Conclusions: Patients with EO-CRC do not have an increased risk of advanced neoplasia compared with patients with AO-CRC and therefore do not require more frequent colonoscopy surveillance than current guidelines recommend., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19., Methods: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up., Results: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up., Conclusions: In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second "salvage" FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials., (©2023 American Association for Cancer Research.)

Background & Aims: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs., Methods: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured., Results: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds., Conclusions: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted., Clinicaltrials: gov, Number: NCT00102011., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: Lynch syndrome (LS)-associated colorectal cancer (CRC) is characterized by mismatch repair-deficiency (MMR-D) and/or microsatellite instability (MSI). However, with increasing utilization of germline testing, MMR-proficient (MMR-P) and/or microsatellite stable (MSS) CRC has also been observed. We sought to characterize MMR-P/MSS CRC among patients with LS., Methods: Patients with solid tumors with germline MMR pathogenic/likely pathogenic (P/LP) variants were identified on a prospective matched tumor-normal next-generation sequencing (NGS) protocol. CRCs were evaluated for MMR-D via immunohistochemical (IHC) staining and/or MSI via NGS. Clinical variables were correlated with MMR status using nonparametric tests., Results: Among 17,617 patients with solid tumors, 1.4% (n = 242) had LS. A total of 36% (86 of 242) of patients with LS had at least one CRC that underwent NGS profiling, amounting to 99 pooled CRCs assessed. A total of 10% (10 of 99) of CRCs were MMR-P, with 100% concordance between MSS status and retained MMR protein staining. A total of 89% (8 of 9) of patients in the MMR-P group had MSH6 or PMS2 variants, compared with 30% (23 of 77) in the MMR-D group ( P = .001). A total of 46% (6 of 13) of PMS2+ patients had MMR-P CRC. The median age of onset was 58 and 43 years for MMR-P and MMR-D CRC, respectively ( P = .07). Despite the later median age of onset, 40% (4 of 10) of MMR-P CRCs were diagnosed <50. A total of 60% (6 of 10) of MMR-P CRCs were metastatic compared with 13% (12 of 89) of MMR-D CRCs ( P = .002). A total of 33% (3 of 9) of patients with MMR-P CRC did not meet LS testing criteria., Conclusion: Patients with LS remained at risk for MMR-P CRC, which was more prevalent among patients with MSH6 and PMS2 variants. MMR-P CRC was later onset and more commonly metastatic compared with MMR-D CRC. Confirmation of tumor MMR/MSI status is critical for patient management and familial risk estimation.

Purpose: The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC., Methods: A retrospective review of patients with CRC diagnosed between ages 20 and 49 years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis. Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record., Results: We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4)., Conclusion: Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Spontaneous chylous effusions are rare; however, they have been observed by independent investigators in patients treated with RET tyrosine kinase inhibitors (TKIs)., Methods: This multicenter, retrospective study evaluated the frequency of chylous effusions in patients treated with RET TKIs. Clinicopathologic features and management of patients with chylous effusions were evaluated., Results: A pan-cancer cohort of 7517 patients treated with one or more multikinase inhibitor or selective RET TKI and a selective TKI cohort of 96 patients treated with selpercatinib or pralsetinib were analyzed. Chylous effusions were most common with selpercatinib (7%), followed by agerafenib (4%), cabozantinib (0.3%), and lenvatinib (0.02%); none were observed with pralsetinib. Overall, 12 patients had chylothorax, five had chylous ascites, and five had both. Time from TKI initiation to diagnosis ranged from 0.5 to 50 months. Median fluid triglyceride level was lower in chylothoraces than in chylous ascites (397 mg/dL [interquartile range: 304-4000] versus 3786 mg/dL [interquartile range: 842-6596], p = 0.035). Malignant cells were present in 13% (3 of 22) of effusions. Chyle leak was not identified by lymphangiography. After initial drainage, 76% of patients with chylothorax and 80% with chylous ascites required additional interventions. Selpercatinib dose reduction and discontinuation rates in those with chylous effusions were 47% and 0%, respectively. Median time from diagnosis to disease progression was not reached (95% confidence interval: 14.5-undefined); median time from diagnosis to TKI discontinuation was 11.4 months (95% confidence interval: 8.2-14.9)., Conclusions: Chylous effusions can emerge during treatment with selected RET TKIs. Recognition of this side effect is key to prevent potential misattribution of worsening effusions to progressive malignancy., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Recurrent Clostridiodies difficile infection (CDI) contributes to morbidity and mortality in cancer patients. Fecal microbiota transplantation (FMT) has been proven to be effective in treatment of recurrent CDI, but immunocompromised patients have been excluded from prospective studies due to safety concerns. The aim of this study was to investigate the safety of FMT for recurrent CDI in immunocompromised patients with solid tumor malignancy undergoing chemotherapy., Methods: This was a single center, prospective observational study of patients at a tertiary care cancer center of 10 patients with recurrent CDI who were at least 18 years of age, with a solid tumor malignancy who had received chemotherapy within the previous 6 months. Patients received FMT either by upper endoscopy or colonoscopy and were followed for 6 months. Safety was a primary outcome measured by infections occurring within 2 weeks of FMT. Efficacy of FMT was also evaluated., Results: Nineteen patients were evaluated. On applying exclusion criteria, 10 were included in the study. One patient requested to be off study within 2 weeks and was considered a treatment failure. Seven received FMT via upper endoscopy, three via colonoscopy. There were no infectious complications from FMT. Eight patients (80%) were cured after the first FMT. All eight patients went on to restart oncologic treatment with an average of 32.5 days after FMT., Conclusions: FMT is safe and effective for recurrent CDI in solid tumor patients undergoing chemotherapy. Patients can resume oncologic treatment after FMT., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and study aims  There are limited data on the success of endoscopic retrograde cholangiopancreatography (ERCP) in patients with malignant biliary and duodenal obstruction with a preexisting duodenal stent. The aim of this study was to evaluate patient and procedural outcomes of a cohort of patients with preexisting duodenal stents who underwent an attempt at ERCP for malignant biliary obstruction (MBO). Patients and methods  This was a single-center retrospective study on consecutive patients with a preexisting duodenal stent who underwent attempted ERCP for MBO. Technical success was defined as successful cannulation of the common bile duct, with successful dilation and/or deployment of a biliary stent under fluoroscopy. Clinical success was defined as number of patients in the entire group who underwent ERCP successfully with resolution of symptoms. Results  We identified 64 patients (73 % men, 74 % white, median age 62 years) with a preexisting duodenal stent who underwent 85 attempts at ERCP. ERCP was technically successful in 50 of 85 procedures (59 %). Overall ERCP was successful in 41 of 85 patients (48 %). ERCP was more likely to be successful in patients with Type 1 and 3 duodenal strictures than with Type 2 strictures (83 % and 92 % vs. 42 %, P  < 0.01), in patients with a preexisting sphincterotomy (79% vs. 20 %, P  = 0.01) or preexisting biliary stent (66 % vs. 34 %, P  = 0.04). Adverse events included bleeding (n = 3), post-procedure fever (n = 3) and abdominal pain (n = 1). Conclusions  Although biliary stenting via ERCP is often technically challenging in patients with a prior duodenal stent, it is a safe and effective method of biliary drainage. ERCP should be attempted in patients with Type 1 and 3 duodenal strictures, a prior sphincterotomy or an indwelling biliary stent., 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: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8-16% and 7%, respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients., Methods: Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD. EGD and pathology reports were extracted manually., Results: Our cohort included 247 patients with a mean age of 47.1 years (SD 12.6) at first EGD. Patients had a mean of 3.5 EGDs (range 1-16). Mean duration of follow-up was 5.7 years. Average interval between EGDs was 2.3 years. Surveillance EGD detected precursor lesions in 8 (3.2%) patients, two (0.8%) gastric cancers and two (0.8%) duodenal cancers. Two interval cancers were diagnosed: a duodenal adenocarcinoma was detected 2 years, 8 months after prior EGD and a jejunal adenocarcinoma was detected 1 year, 9 months after prior EGD., Conclusions: Our data suggest that surveillance EGD is a useful tool to help detect precancerous and cancerous upper GI lesions in LS patients. To our knowledge, this is the first study to examine a program of surveillance EGDs in LS patients. More data are needed to determine the appropriate surveillance interval., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aims: The coronavirus disease of 2019 (COVID-19) pandemic has impacted the training of medical trainees internationally. The aim of this study was to assess the global impact of COVID-19 on endoscopy training from the perspective of endoscopy trainers and to identify strategies implemented to mitigate the impact on trainee education., Methods: Teaching faculty of gastroenterology (GI) training programs globally were invited to complete a 36-question web-based survey to report the characteristics of their training programs and the impact of COVID-19 on various aspects of endoscopy training, including what factors decisions were based on., Results: The survey response rate was 52.6% (305 out of 580 individuals); 92.8% reported a negative impact on endoscopy training, with suspension of elective procedures (77.1%) being the most detrimental factor. Geographic variations were noted, with European programs reporting the lowest percentage of trainee participation in procedures. A higher proportion of trainees in the Americas were allowed to continue performing procedures, and trainers from the Americas reported receiving the greatest support for endoscopy teaching., Conclusion: This study demonstrated that the COVID-19 pandemic has had a significant negative impact on GI endoscopy training internationally, as reported by endoscopy trainers. Focus-optimizing endoscopy training and assessment of competencies are necessary to ensure adequate endoscopy training.

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., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Disparities observed in colorectal cancer (CRC) incidence and mortality among blacks and Hispanics compared with whites may be in part due to lower screening rates. The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has implemented a patient navigator (PN) program at NYC hospitals serving lower-income patients to promote high adherence by patients referred for screening colonoscopy. A prior study showed this PN program increased adherence at 3 public hospitals. The aim of this study was to determine the feasibility of expanding the PN program to 10 hospital sites by assessing the impact of the PN program on adherence to screening colonoscopy in a large, urban, lower-income population., Methods: Data were collected from 2007 through the first quarter of 2012 from PN sites. One site also contributed data from the pilot phase of the project, from 2005 to 2006. Adherence to scheduled screening colonoscopy among those ≥ 50 years was assessed among 10 hospital sites in NYC participating in the colonoscopy PN program., Results: Among the 37,077 asymptomatic adults ≥ 50 years who were scheduled for a screening colonoscopy from 2005 to the first quarter of 2012, 84.2% (83.2% of black, 84.9% of Hispanic, and 87.5% of white adults) were adherent to scheduled colonoscopy., Conclusions: Expansion of PN programs to navigate all patients referred for a colonoscopy was feasible in a large, urban setting. This can be implemented resulting in high overall adherence rates to screening colonoscopies. The program likely did not result in large ethnic disparities.

Background & Aims: Practices dramatically reduced endoscopy services due to the COVID-19 pandemic. Because practices now are considering reintroduction of elective endoscopy, we conducted a survey of North American practices to identify reactivation barriers and strategies., Methods: We designed and electronically distributed a web-based survey to North American gastroenterologists consisting of 7 domains: institutional demographics, impact of COVID-19 on endoscopy practice, elective endoscopy resumption plans, anesthesia modifications, personal protective equipment policies, fellowship training, and telemedicine use. Responses were stratified by practice type: ambulatory surgery center (ASC) or hospital-based., Results: In total, 123 practices (55% ASC-based and 45% hospital-based) responded. At the pandemic's peak (as reported by the respondents), practices saw a 90% decrease in endoscopy volume, with most centers planning to resume elective endoscopy a median of 55 days after initial restrictions. Declining community prevalence of COVID-19, personal protective equipment availability, and preprocedure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing availability were ranked as the 3 primary factors influencing reactivation timing. ASC-based practices were more likely to identify preprocedure testing availability as a major factor limiting elective endoscopy resumption (P = .001). Preprocedure SARS-CoV-2 testing was planned by only 49.2% of practices overall; when testing is performed and negative, 52.9% of practices will continue to use N95 masks., Conclusions: This survey highlights barriers and variable strategies for reactivation of elective endoscopy services after the COVID-19 pandemic. Our results suggest that more widespread access to preprocedure SARS-CoV-2 tests with superior performance characteristics is needed to increase provider and patient comfort in proceeding with elective endoscopy., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Study Aims: Corona virus disease-19 (COVID-19) pandemic has markedly impacted routine medical services including gastrointestinal (GI) endoscopy. We aim to report the real-life performance in high volume GI endoscopy units during the pandemic., Patients and Methods: A web-based survey covering all aspects of daily performance in GI endoscopy units was sent to endoscopy units worldwide. Responses were collected and data were analyzed to reveal the effect of COVID-19 pandemic on endoscopy practice., Results: Participants from 48 countries (n = 163) responded to the survey with response rate of 67.35%. The majority (85%) decreased procedure volume by over 50%, and four endoscopy units (2.45%) completely stopped. The top three indications for procedures included upper GI bleeding (89.6%), lower GI bleeding (65.6%) and cholangitis (62.6%). The majority (93.9%) triaged patients for COVID-19 prior to procedure. N95 masks were used in (57.1%), isolation gowns in (74.2%) and head covers in (78.5%). Most centers (65%) did not extend use of N95 masks, however 50.9% of centers reused N95 masks. Almost all (91.4%) centers used standard endoscopic decontamination and most (69%) had no negative pressure rooms. Forty-two centers (25.8%) reported positive cases of SARS-CoV-2 infection among patients and 50 (30.7%) centers reported positive cases of SARS-CoV-2 infection among their healthcare workers., Conclusions: Most GI endoscopy centers had a significant reduction in their volume and most procedures performed were urgent. Most centers used the recommended personal protective equipment (PPE) by GI societies however there is still a possibility of transmission of SARS-CoV-2 infection in GI endoscopy units., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic seemingly is peaking now in New York City and has triggered significant changes to the standard management of gastrointestinal diseases. Priorities such as minimizing viral transmission, preserving personal protective equipment, and freeing hospital beds have driven unconventional approaches to managing gastroenterology (GI) patients. Conversion of endoscopy units to COVID units and redeployment of GI fellows and faculty has profoundly changed the profile of most GI services. Meanwhile, consult and procedural volumes have been reduced drastically. In this review, we share our collective experiences regarding how we have changed our practice of medicine in response to the COVID surge. Although we review our management of specific consults and conditions, the overarching theme focuses primarily on noninvasive measures and maximizing medical therapies. Endoscopic procedures have been reserved for those timely interventions that are most likely to be therapeutic. The role of multidisciplinary discussion, although always important, now has become critical. The support of our faculty and trainees remains essential. Local leadership can encourage well-being by frequent team check-ins and by fostering trainee development through remote learning. Advancing a clear vision and a transparent process for how to organize and triage care in the recovery phase will allow for a smooth transition to our new normal., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: The risk of immune checkpoint inhibitor therapy-related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors., Patients and Methods: We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events., Results: Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn's disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event-related deaths were recorded. Anti-cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively)., Conclusion: Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use and can significantly impact quality of life, especially in patients with advanced illness. Methylnaltrexone has proven effective in treating cancer patients with OIC who have not responded adequately to conventional laxative therapy, though use is relatively contraindicated in those with peritoneal carcinomatosis due to theoretical risk and reported cases of perforation. The aim of this study was to evaluate the safety of methylnaltrexone in patients with carcinomatosis. We performed a retrospective review of 3058 pediatric and adult patients who received methylnaltrexone at Memorial Sloan Kettering Cancer Center from 2009-2016. Data collected included age, cancer diagnosis, history of abdominal surgery, prior radiation therapy, evidence of peritoneal carcinomatosis, and complications. Charts were reviewed for any complications at 24 hours, 72 hours, and one week following drug administration, as well as at present. We identified 3058 patients (median age 56, range 1-95) who received a total of 3995 doses of methylnaltrexone. Three hundred thirty three (median age 55, range 4-88) had peritoneal carcinomatosis. The most common primary malignancies included pancreatic (17.7%), ovarian (13.5%), colon (7.2%), and lung (6.6%). 228/333 (68.4%) had a history of abdominal surgery and 85/333 (25.5%) underwent prior radiation therapy. Three patients had adverse outcomes or complications, with only one (0.3%) thought to be related to methylnaltrexone use. To our knowledge, this is the largest study to evaluate the outcomes of patients with carcinomatosis receiving methylnaltrexone and the first to include pediatric patients. We found one perforation attributed to methylnaltrexone. Methylnaltrexone should be considered for treatment of refractory OIC in cancer patients with peritoneal carcinomatosis due to low risk of complications.

Following initial successes in melanoma treatment, immunotherapy has rapidly become established as a major treatment modality for multiple types of solid cancers, including a subset of colorectal cancers (CRCs). Two programmed cell death 1 (PD1)-blocking antibodies, pembrolizumab and nivolumab, have shown efficacy in patients with metastatic CRC that is mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H), and have been granted accelerated FDA approval. In contrast to most other treatments for metastatic cancer, immunotherapy achieves long-term durable remission in a subset of patients, highlighting the tremendous promise of immunotherapy in treating dMMR-MSI-H metastatic CRC. Here, we review the clinical development of immune checkpoint inhibition in CRC leading to regulatory approvals for the treatment of dMMR-MSI-H CRC. We focus on new advances in expanding the efficacy of immunotherapy to early-stage CRC and CRC that is mismatch-repair-proficient and has low microsatellite instability (pMMR-MSI-L) and discuss emerging approaches for targeting the immune microenvironment, which might complement immune checkpoint inhibition.

Background: Direct percutaneous endoscopic jejunostomy (DPEJ) is used for enteral nutrition (EN) in patients with postoperative anastomotic leaks after esophagectomy/gastrectomy and at high risk for aspiration. We characterized the indications, technical success, procedural/nutrition outcomes, and adverse events in a large cohort of patients undergoing DPEJ insertion., Methods: Patients undergoing DPEJ insertion between January 2009 and March 2015 were identified from an institutional endoscopy database. Demographic, procedural, and nutrition outcome data were collected from electronic medical records. Regression analyses were used to identify predictors of adverse events and procedural success., Results: A total of 452 patients underwent 480 attempts at DPEJ insertion. Indications included preoperative or postoperative weight loss (64%), postoperative upper gastrointestinal (UGI) anastomotic leak (13%), aspiration prevention (10%), and other (13%). Of attempted procedures, 398 (83%) were successful. Feeding was initiated in 389 (98%) of patients; a median of 1775 calories was delivered daily. Median body mass index (BMI) at baseline was 22.9 (11.4-44.7) and did not change over follow-up. Median change in BMI after DPEJ was similar in groups that received EN with palliative and curative intent. Adverse events following 480 attempted DPEJ insertions included 13 (3%) immediate and 74 (15%) delayed, 13 (3%) of which were serious. Patients with head and neck cancer had more adverse events than those with esophageal cancer (P = .020)., Conclusion: DPEJ is a successful and safe procedure that effectively provides access for EN support in malnourished patients and patients with postoperative UGI cancer., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: The frequency of mismatch repair (MMR) deficiency (dMMR) in patients < 50 years with adenomas without a known germline mutation is unknown. Our aim was to define the frequency of dMMRs in adenomas from patients aged < 50 years., Patients and Methods: We identified all patients aged 18 to 49 years who had undergone colonoscopy at Memorial Sloan Kettering Cancer Center from 2008 to 2013 and were identified as having tubular, villous, or tubulovillous adenomas on pathology. Patients with a personal history of colorectal cancer, polyposis syndrome, or inflammatory bowel disease before colonoscopy were excluded. Age, demographic data, family history of cancer, personal history of cancer, use of radiation, reason for colonoscopy, and colonoscopy findings were recorded. Polyps were stained using immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 proteins., Results: A total of 208 patients with 266 polyps were identified. Of the 266 polyps, 259 could be stained. Of the 208 patients, 82 (40%) were men; their mean age was 44 years. The indication for colonoscopy was screening for 120, diagnostic for 75, and therapeutic for 15. Of the 259 examined polyps, 246 (95%) were tubular adenomas and 13 were tubulovillous adenomas (5%). One patient (0.4%) was found to have dMMRs in 1 polyp. This patient was a 42-year-old woman with a history of endometrial cancer who had undergone colonoscopy for hematochezia. A 15-mm transverse tubular adenoma was found that was deficient in MLH1 and PMS2., Conclusion: Our results indicate that routine screening of polyps in patients aged < 50 years old is not an effective tool for identifying Lynch syndrome carriers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients with prior pancreaticobiliary or distal gastric cancer treated surgically may have local anastomotic recurrence with obstruction of the afferent and efferent jejunal limbs. This report describes the efficacy and safety of simultaneous endoscopic insertion of self-expanding metal stents into the afferent and efferent jejunal limbs in patients with gastric outlet obstruction (GOO) of post-surgical anatomy for palliation of recurrent malignancy., Methods: Patients were identified from an endoscopic database at a specialized cancer center between September 2007 and March 2014. Technical success was defined as single-session insertion of afferent and efferent jejunal limb enteral stents. Clinical success was defined as immediate symptom relief and ability to advance diet. A durable response was defined as symptom relief of at least 60 days or until hospice placement or death., Results: Twenty-three patients were identified who underwent insertion of two 22-mm-diameter uncovered duodenal stents. Stent length varied from 60 to 120 mm. Stents were placed under endoscopic and fluoroscopic guidance. Three patients required balloon dilation to facilitate stent insertion. Average procedure time was 58.8 min (range 28-120). Technical success was achieved in 23/24 (96%) patients. Clinical success was achieved in 19/23 (83%) patients. Following initial stent insertion and prior to subsequent re-intervention, 11/19 (58%) patients had a durable response with a median duration of 70 days (range 4-315). Eight (42%) patients underwent subsequent re-intervention at a median of 22 days (range 11-315). Five patients had stent revision and were able to tolerate oral intake. Two patients had percutaneous endoscopic gastrostomy/jejunostomy insertion. One patient required surgical diversion for persistent obstruction. Complications included stent migration and post-stent insertion bacteremia due to food bolus obstruction., Conclusions: Recurrent malignant GOO in patients with post-surgical anatomy treated with simultaneous endoscopic enteral stenting of afferent and efferent jejunal limbs has a high rate of technical and clinical success and low rate of complications and provides effective palliation.

Background: Esophageal anastomotic leaks after cancer surgery remain a major cause of morbidity and mortality. Endoscopic interventions, including covered metal stents (cSEMS), clips, and direct percutaneous endoscopic jejunostomy (dPEJ) tubes are increasingly used despite limited published data regarding their utility in this setting. This study aimed to determine the efficacy and safety of a multimodality endoscopic approach to anastomotic leak management after operation for esophageal or gastric cancer., Methods: We performed a retrospective review of prospectively maintained databases of gastric and esophageal operations at our hospital between January 2003 and December 2012. Included patients had an operation for esophageal or gastric cancer, demonstrated evidence of an anastomotic leak at the esophageal anastomosis, and underwent attempted endoscopic therapy. Healing was defined as clinical and radiographic leak resolution., Results: Forty-nine patients with leaks underwent endoscopic management. Of the 49 patients, 31 (63%) received cSEMS, 40 (82%) had dPEJ tubes inserted, and 3 (6%) received clips. Twenty-three (47%) patients underwent a combined approach. Overall, 88% of patients achieved healing in a median of 83 days. Twenty-two of 23 patients (96%) who underwent a multimodality endoscopic approach healed. Only 1 patient had a major complication associated with stent erosion into the pulmonary artery, which was successfully treated with operative repair., Conclusions: Esophageal anastomotic leaks after esophageal and gastric cancer operations can be managed successfully and safely with endoscopic therapy. Combining cSEMS for leak control and dPEJ tube placement for nutritional support was highly effective in achieving healing, without the need for surgical repair., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Controversy exists regarding whether to place a plastic or a metal endobiliary stent in patients with resectable pancreatic cancer who require biliary drainage. Although self-expandable metal stents (SEMS) provide better drainage compared with plastic stents, concerns remain that SEMS may compromise resection and increase postoperative complications. Our objective was to compare surgical outcomes of patients undergoing pancreaticoduodenectomy (PD) with SEMS in place vs. plastic endoscopic stents (PES) and no stents (NS)., Methods: We performed a retrospective analysis from a prospective database of all patients undergoing either attempted or successful PD with SEMS, PES, or NS in place at the time of operation. Patients were compared with regard to perioperative complications, margin status, and the rate of intraoperative determination of unresectability., Results: A total of 593 patients underwent attempted PD. Of these, 84 patients were locally unresectable intraoperatively and 509 underwent successful PD, of which 71 had SEMS, 149 had PES, and 289 had NS. Among patients who had a preoperative stent, SEMS did not increase overall or serious postoperative complications, 30-day mortality, length of stay, biliary anastomotic leak, or positive margin, but was associated with more wound infections and longer operative times. In those with adenocarcinoma, intraoperative determination of local unresectability was similar in the SEMS group compared with other groups, with 16 (19.3%) in SEMS compared with 29 (17.7%) in PES (P=0.862), and 31 (17.5%) in NS (P=0.732)., Conclusions: Placement of SEMS is not contraindicated in patients with resectable pancreatic cancer who require preoperative biliary drainage.

Background: Endoscopically inserted self-expandable metal stents (SEMSs) are used to palliate malignant gastric outlet obstruction (GOO). Peritoneal disease is considered a relative contraindication to SEMS placement given the risk of multifocal obstruction., Objective: To evaluate the success of SEMSs placed in patients with GOO with carcinomatosis., Design: Retrospective review of patients who underwent SEMS placement for malignant GOO., Setting: Large, urban cancer center., Patients: A total of 215 patients who were scheduled for SEMS placement for GOO., Interventions: SEMS placement., Main Outcome Measurements: Technical success, clinical success, early and late SEMS failure, and complications., Results: Technical success was achieved in 192 of 201 patients (95.5%). Of the 9 patients who did not achieve technical success, 6 had carcinomatosis. Among the 116 patients (60%) with carcinomatosis, clinical success was achieved 94 of them (81%). Of these 94 patients, 17 (18%) required reinterventions: 4 for early SEMS failure and 13 for late SEMS failure. Among the 76 patients (40%) without carcinomatosis, clinical success was achieved in 64 of them (84%). Of these 64 patients, 17 (27%) required reinterventions: 4 for early SEMS failure and 13 for late SEMS failure. Complication rates were similar for both groups., Limitations: This was a retrospective review with experienced clinicians selecting patients whom they thought would benefit from SEMS placement., Conclusions: This is the first study to evaluate the effect of carcinomatosis on the technical and clinical success of SEMSs in the palliation of malignant GOO. We found clinical outcomes comparable to those without peritoneal disease. Carcinomatosis should not be considered a contraindication to SEMS placement in selected patients with malignant GOO., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)