Search

The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC.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.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).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.

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.

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.

The increase in young onset colorectal cancer and the complex care needs of young cancer patients spurred the development of the Center for Young Onset Colorectal Cancer at the Memorial Sloan Kettering Cancer Center. This article describes the lessons of the first 2 years at the Center, including development of the program and specific services provided.

Spontaneous chylous effusions are rare; however, they have been observed by independent investigators in patients treated with RET tyrosine kinase inhibitors (TKIs).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.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).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.

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.

INTRODUCTION: Disparities observed in colorectal cancer (CRC) incidence and mortality among blacks and Hispanics compared to 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 2005–2006. 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.

Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal antibody used in the treatment of cervical cancer, ovarian cancer, colorectal cancer, lung cancer, renal cell cancer, and recurrent glioblastomas. Its approval by US FDA was issued with a black box warning that its use has been associated with a risk of gastrointestinal (GI) tract perforation and that it should be discontinued in patients who have experienced such. The reported incidence of GI perforation in those receiving bevacizumab is as high as 3%. However, the incidence of GI perforation in those receiving bevacizumab undergoing GI endoscopic procedures has not been well studied. A retrospective, single-center observational study was conducted at Memorial Sloan Kettering Cancer Center (MSKCC) between 2011 and 2018. All patients who underwent upper GI endoscopy with percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ) tube placement and received bevacizumab within 6 months of their endoscopic procedure were included. We identified 176 patients who underwent PEG or PEJ tube placement and received bevacizumab within 6 months. Eighty-one percent of patients were female (n = 144) and the median age was 61 years. Prior to endoscopic procedures, patients received a median of seven doses of bevacizumab. Patients received bevacizumab from 170 days before to 170 days after their endoscopic procedures (median 44 days). No GI perforations were observed during or after the time of the endoscopic procedures. Our study demonstrated that receiving bevacizumab within 6 months prior to their endoscopic procedure was not associated with an increased risk of GI tract perforation and thus not an absolute contraindication to proceeding with PEG and PEJ tube placement in these patients.

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.

Background The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC). Methods Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided. Results In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P Conclusions EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted.

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 & 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.

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.

BackgroundThe prevalence and significance of digestive manifestations in COVID-19 remain uncertain.MethodsConsecutive 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 manually abstracted 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.ResultsA total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one 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 elevated 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% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death.ConclusionsAmong 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

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 fecal microbiota transplantation (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, 3 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.

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.

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.

Colonic stent placement in patients with large-bowel obstruction (LBO) secondary to extracolonic malignancy (ECM) has been evaluated in small series with heterogeneous results. Our aim is to better characterize the technical and clinical success of colonic stent placement and to identify factors that affect this success in ECM patients.All patients at a single high-volume center who presented for colonic stent placement for LBO because of ECM between 2001 and 2012 were retrospectively identified. The outcomes of interest were technical success, clinical success, stent occlusion rate, and overall survival.A total of 187 patients were identified. Mean age was 61.9 years (range, 23-89), and 150 (80.2%) were women. The most common malignancy type was urogynecologic (n = 104) and most common location sigmoid colon (n = 128). Overall, 142 patients (75.9%) achieved technical success and 102 patients (54.5%) clinical success. Radiographic presence of peritoneal carcinomatosis (P .001) and multifocal disease (P .001) were associated with both decreased technical and clinical success. Procedure-related adverse events were seen in 12 patients (6.4%). In patients with clinical success, the incidence of stent occlusion at 3 months was 14.7% (95% confidence interval, 7.8%-21.6%) and was higher in patients with prior radiation therapy (P = .011). The median overall survival for all patients from time of attempted stent placement was 3.3 months (95% confidence interval, 3.0-4.1).This study represents the largest retrospective series of colonic stent placement for LBO in ECM patients in the literature. Our technical success rate of 75.9%, clinical success rate of 54.5%, and 3-month stent occlusion rate of 14.7% suggest that stent placement is a viable palliative option for patients with advanced disease because of ECM. Patients with peritoneal carcinomatosis and multifocal disease have reduced technical and clinical success. However, these factors should not dissuade an attempt at stent placement, if risk-to-benefit analysis is favorable.

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.

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.

e16070 Background: Intestinal dysbiosis has been hypothesized as a possible etiology of the increasing incidence of early-onset colon cancer (EO-CC). Here, we compare the microbiome signature in nonmetastatic, microsatellite stable (MSS) EO-CC to average-onset colon cancer (AO-CC). Methods: Specimens from patients with resected stage I-III MSS colon cancer from 2014-2019 were sequenced by MSK-IMPACT, a large panel next generation sequencing (NGS) assay. A validated technique using non-human read sequences from NGS analysis was used to identify the microbial species in tumor tissue. The tumor microbial alpha diversity and differentially abundant microbiome were compared between patients younger than 40 years (EO-CC) with those older than 60 years (AO-CC). Results: Of 275 patients with MSS, 24 (mean 33.6, range 24-39) and 114 patients (mean 70, range 61-90) had EO-CC and AO-CC, respectively. There was no significant difference in clinicopathological features including gender, tumor stage and neoadjuvant treatment between the two groups. EO-CC was more likely to present with left sided disease compared to AO-CC (81% vs. 45%, p = 0.001). There was no significant difference in the tumor microbial diversity (alpha diversity) between the EO-CC and AO-CC (pShannon= 0.95). Although there was a relative abundance of microbial species from bacterial phylum such as Actinobacteria, Deinococcus-Thermus, α-proteobacteria, γ-proteobacteria and δ-proteobacteria in EO-CC compared to AO-CC, this difference was not significant after controlling for multiple comparisons (Table). Conclusions: Our analysis did not reveal a significant difference between EO-CC and AO-CC in both the abundance and diversity of tumor microbial species, suggesting intestinal dysbiosis may not be a major driver in early onset colorectal cancer pathogenesis. However, additional studies with a larger sample size are warranted for further analysis and subgroup comparison. [Table: see text]

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. 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. 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. 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.

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.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.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.Our results indicate that routine screening of polyps in patients aged 50 years old is not an effective tool for identifying Lynch syndrome carriers.

Is the higher reported colorectal cancer (CRC) mortality in blacks versus whites in the United States due to pathology or disparities in screening? Our study used patient navigation (PN) to assist blacks and whites adhere to screening colonoscopy and compared adenomas detected in each group.

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.

3520Background: The incidence of CRC in patients (pts) under the age of 50 has been rising over the past decade. Little is known about the biologic differences between early and AO (over the age of...

The aim of this study was to evaluate the feasibility and early safety of catheter-directed irreversible electroporation (IRE) of the normal common bile duct (CBD) in swine.IRE (2000 V, 90 pulses, 100 μs pulse) was performed in the CBD of 6 Yorkshire pigs using a catheter electrode under endoscopic guidance. Ductal patency was assessed with immediate retrograde cholangiography and contrast-enhanced CT imaging at 1 or 7 days after treatment. Animals were killed at either 1 day (n = 4, 2 ablations/animal) or 7 days (n = 2, 1 ablation/animal) after treatment. The biliary tract was extracted en bloc and the length of the ablation along the CBD mucosa was measured. The depth of ablation was quantified using cross-sections of the treated CBD wall stained with hematoxylin and eosin. Single-sample hypothesis testing was performed to verify whether the depth of ablation in the CBD was a representative outcome of IRE treatment.IRE of the CBD did not result in perforation or obstruction of the organ at 1 or 7 days after treatment. The length of ablation along the CBD mucosa was 17.27 ± 5.55 mm on day 1 samples, and transmural ablation of the CBD wall was a representative outcome of the treatment (7/8 samples, P .05). Day 1 samples demonstrated loss of epithelium, transmural necrosis, with preservation of lumen integrity. Day 7 samples demonstrated re-epithelialization, with diffuse transmural fibrosis of the CBD wall. These findings were absent from sham tissue samples.Intraluminal catheter-directed IRE is feasible and safe for full-thickness ablation of the normal porcine CBD without affecting lumen patency up to 1 week after treatment.

Mono-allelic germline mutations in DNA mismatch repair (MMR) genes lead to Lynch syndrome (LS). Questions remain as to the timing of the inactivation of the wild-type allele in LS-associated tumorigenesis. Speculation exists that it happens after the neoplasia has been initiated. However, a recent study reported the presence of MMR-deficiency in non-neoplastic colonic crypts in LS; thus the possibility can be raised that these crypts may be tumor precursors, and as such, biallelic loss of MMR may occur prior to neoplasia. Here we report a unique case that showed findings supporting both of the two seemingly conflicting notions. The patient was a 40-year-old female with LS, MSH2 type, who underwent a segmental colectomy for an adenocarcinoma. By immunohistochemistry, the carcinoma lost MSH2/MSH6. Interestingly, there was also complete loss of MSH2/MSH6 in a distinct focus of 20 colonic crypts that were morphologically non-neoplastic, thus supporting the possibility of biallelic loss of MMR before initiation of neoplasia. However, in a separate adenoma, MMR was preserved in neoplastic glands with low grade dysplasia and lost only in glands with high grade dysplasia, i.e., MMR loss after tumor initiation. These are relevant findings with regard to the timing of MMR deficiency in LS tumorigenesis, and bring forth the possibility that varied tumorigenic pathways may exist. Additionally, we observed that the MMR-deficient non-neoplastic crypts harbored increased intraepithelial CD8-positive T-lymphocytes similar to the patient’s carcinoma, providing a potential new venue for the study of the natural antitumor immune responses in LS individuals.