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Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.

Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery.We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn'sColitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P.05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration.A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI.Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

Summary Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Background & Aims We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. Methods A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naive and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. Results A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naive and −exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist−treated patients. However, in TNF-antagonist−naive patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Conclusions Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist−naive patients.

OBJECTIVE: To determine the mortality of Crohn’s disease (CD) and ulcerative colitis (UC) and temporal trends in mortality. PATIENTS AND METHODS: All 895 residents of Olmsted County, Minnesota, U.S.A., first diagnosed with inflammatory bowel disease (IBD) (411 CD, 484 UC) between January 1, 1970 and December 31, 2010 were followed through June 30, 2016. Standardized mortality ratios (SMR) were computed—expected rates were derived from the US 2010 background population. To determine overall and cause-specific mortality, each IBD patient was matched with five county residents, and Cox regression analysis was used to assess time to death. RESULTS: A total of 895 IBD patients and 4475 non-IBD patients were included. Seventy-four CD patients died compared with 59.2 expected (SMR, 1.25; 95%confidence interval [CI], 0.98-1.57), and 77 UC patients died compared with 108.1 expected (SMR, 0.71; 0.56-0.89). In CD, the risk of dying was significantly associated with calendar period of diagnosis 1970-79 (SMR, 1.90; 1.24-2.78). Among those diagnosed after calendar period of 1980, the risk of dying in CD patients was similar to the US background population. In UC, the risk of dying was less than expected in all groups of calendar period of diagnosis. In the Cox regression analysis, overall mortality was not significantly higher among CD (HR, 1.26; 95% CI, 0.97-1.63) or UC patients (HR, 0.89; 0.70-1.14) compared to the comparison cohort. The risk of dying from digestive diseases (HR, 3.70; 95%CI, 1.24-11.0) and respiratory diseases (HR, 2.72; 1.36-5.44) was increased in CD but not UC. CONCLUSION: In this cohort, overall mortality among CD patients diagnosed after calendar period of 1980 did not differ from that of the US background population. Overall mortality in UC patients diagnosed in the calendar period of 1970-2010 was lower than the expected mortality.

Background & Aims In women with inflammatory bowel diseases (IBDs), exposure to immunomodulator or biologic therapy has not been associated with adverse events during pregnancy or outcomes of newborns. We investigated whether exposure of patients to these agents during pregnancy affects serologic responses to vaccines in newborns. Methods We collected data from the Pregnancy in IBD and Neonatal Outcomes registry, which records outcomes of pregnant women with diagnosis of IBD receiving care at multiple centers in the United States, from 2007 through 2016. Serum samples collected from infants at least 7 months old were analyzed for titers of antibodies to Haemophilus influenzae B (HiB) or tetanus toxin; mothers completed a survey of vaccine practices and outcomes from July 2013 through October 2016. Umbilical cord blood samples from 33 infants were assayed for concentration of biologic agents. Vaccination response was compared between infants born to mothers exposed to biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, natalizumab, vedolizumab, or ustekinumab—either as a single agent or in combination with an immunomodulator, at any time between conception and delivery) and infants born to unexposed mothers. Results A total of 179 women completed the vaccine survey (26 biologic unexposed, 153 exposed to a biologic agent). We found no significant difference in proportions of infants with protective antibody titers against HiB born to exposed mothers (n = 42, 71%) vs unexposed mothers (n = 8, 50%) ( P = .41). We also found no difference in the proportion of infants with protective antibody titers to tetanus toxoid born to exposed mothers (80%) vs unexposed mothers (75%) ( P = .66). The median concentration of infliximab in cord blood did not differ significantly between infants with vs without protective antibody titers to HiB ( P = .30) or tetanus toxoid ( P = .93). Mild reactions were observed in 7/40 infants who received rotavirus vaccine and whose mothers had been exposed to biologic therapies. Conclusions Vaccination of infants against HiB and tetanus toxin, based on antibody titers measured when infants were at least 7 months old, does not appear to be affected by in utero exposure to biologic therapy.

Many factors influence the sexual health of people with Crohn's disease, but active disease and depression play key roles. The fertility rate in nonoperated patients with inflammatory bowel disease with quiescent disease is similar to that in the general population. Crohn's disease can increase the risk for adverse pregnancy outcomes, but being in remission on a stable, steroid-free medication regimen for at least 3 months before conception and adhering to the treatment throughout pregnancy can improve outcomes. Infants with intrauterine exposure to anti-tumor necrosis factor medications should avoid live vaccines for the first 9 months or until drug concentrations are undetectable.

Introduction Inflammatory bowel disease (IBD) management is changing at a rapid rate, with the emergence of multiple new therapies and evolving care goals. In addition, the quality and quantity of IBD fellowship education is highly variable, based on patient populations and institutional expertise. Therefore, it is crucial to develop improved ways to educate our trainees. Here, we describe an educational initiative designed to familiarize first year gastroenterology (GI) fellows to key concepts in the management of IBD. Methods IBD 101 is a one-day course designed to introduce first-year GI fellows to various clinical topics relevant to the management of IBD. The program was held on September 14, 2019. Fellows from U.S. allopathic GI training programs were selected by their training directors for participation. The course included small group didactic sessions led by expert faculty members and group observed structured clinical examinations (OSCEs), in which fellows observed encounters between expert faculty and standardized patients followed immediately by debrief sessions to reinforce key concepts. The topics included need for surgery in IBD, pregnancy and IBD, escalation of care for acute severe UC, initiating biologic therapy, treatment of mild-moderate IBD, treatment of moderate-severe IBD and managing loss of response to therapy. A review of supplemental opportunities for education in IBD was presented at the conclusion of the course. Pre- and post-course surveys using Likert scoring (1=“strongly disagree” through 4=“strongly agree”) were administered to assess baseline knowledge and educational impact of the course on each addressed topic. Results 55 fellows from 32 programs participated. 49/55 (89%) completed pre- and post-course surveys to assess the educational impact of the program on the didactic sessions and on the group OSCE format. 100% of fellows felt that the course content was appropriate for their scope of clinical practice. Substantial improvement in comfort with all addressed clinical topics was noted (figure 1). In the post-course survey, all fellows reported an improved ability to manage and treat patients with IBD. Comparing career interest in IBD, more participants expressed interest in pursuing a career in IBD after participating (pre: 63% vs post: 75%). 96% of attendees stated that they would strongly recommend this course to future GI fellows. Conclusions This single day course for first-year GI trainees was effective and well-received, and offers a novel intervention to address the challenges of IBD education and training. Follow-up of this cohort of trainees and expansion for next year is planned.

Background & aimsWe created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC).MethodsWe performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December2017.ResultsAbsence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy.ConclusionsWe used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

The impact of inflammatory bowel disease (IBD) activity and treatment on fertility and pregnancy outcomes is important for men and women. In women, remission at conception determines better pregnancy outcomes,1,2 and most maternal IBD medication exposures are safe.2 In contrast, less is known about the impact of paternal disease activity and medication use on fertility and pregnancy outcomes in men with IBD.3.

Background & Aims There are few real-world data on the safety of vedolizumab for treatment of Crohn’s disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice. Methods We performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs. Results Our analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections. Conclusion In a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections

We performed a prospective study of patients with inflammatory bowel diseases to examine variations in treatment among medical centers. In a prospective cohort study of 1659 patients with CD and 946 patients with UC seen at 7 high-volume referral centers, we collected data on demographics, disease characteristic, and medical and surgical treatments. We used logistic regression to determine differences in treatment among centers, controlling for potential confounders. We found significant variations among centers in treatment of CD with immunomodulators (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.09 – 5.32) but not anti-tumor necrosis factor agents (OR, 1.64; 95% CI, 0.97 – 2.77). There was less variation in treatment of UC; we found no difference in use of immunomodulators (OR,1.83 95% CI, 1.00 – 3.36) or anti-TNF therapy (OR, 0.81; 95% CI, 0.40 – 1.65). Development and implementation of evidence-based standards of care for IBD may help reduce variation and improve outcomes.

Effectiveness of early treatment with biologics and immunomodulator therapy on healthcare utilization remains poorly defined. We assessed rates of hospitalization and surgery within 1 year after initiation of infliximab and/or immunomodulator therapy in a United States cohort of patients with inflammatory bowel disease.We conducted a retrospective, observational cohort study of veterans with Crohn's disease or ulcerative colitis by using administrative data from 176 Department of Veteran Affairs facilities (October 1, 2001 through September 30, 2009). Inpatient, outpatient, and death records were linked longitudinally with prescription fill data. Each person-day of follow-up was assessed for treatment with infliximab, immunomodulators, both (dual therapy), or neither. We calculated drug exposure time and used Poisson and logistic regression analyses to assess outcomes.The cohort of 20,474 patients included 8042 patients with Crohn's disease and 12,432 with ulcerative colitis (93.9% male; 72.5% white; mean age, 60.9 ± 14.5 years) prescribed infliximab (0.17%), immunomodulator (1.3%), or dual therapy (1.5%). Adjusted models revealed 50% relative reductions in hospitalization among patients who received 9.2 months of immunomodulator monotherapy, 8 months of infliximab, or 7.7 months of dual therapy. A 50% relative reduction in surgery was observed among patients receiving 7 months of infliximab or 5 months of dual therapy. Analysis of dose-response data revealed 73.1% and 92% reductions in risk of hospitalization and surgery, respectively, after 9 months of dual therapy.On the basis of a retrospective cohort study, dual therapy with infliximab and an immunomodulator for8 months is associated with significant reductions in hospitalization and surgery within 1 year of the start of therapy. These findings indicate that patients with IBD are more likely to benefit if dual therapy is initiated earlier in their first year of therapy.

Inflammatory bowel diseases are chronic conditions that frequently affect patients during their childbearing years. Considering the characteristics of disease and the medications used to treat it, several issues arise in the care of these patients when they attempt or achieve conception. We review the most current evidence concerning fertility and pregnancy outcomes in patients with inflammatory bowel diseases. With the exception of those women who undergo pelvic surgery, patients with inflammatory bowel diseases have no decreased fertility. Sulfasalazine decreases fertility in men. When looking at obstetrical outcomes, active disease at conception is associated with an increased risk of preterm delivery and low birth weight. While most medications used to treat inflammatory bowel diseases are low risk, some precautions need to be taken and the risk-to-benefit ratio needs to be considered on an individualized basis. In general, aminosalicylates and thiopurines should be continued, but methotrexate is contraindicated. Anti-tumour necrosis factor agents are considered safe to continue but full monoclonal antibodies do cross the placenta. As a general rule, the it is important to counsel women that conception is optimal when disease is in remission, as adverse obstetrical outcomes are directly associated with disease activity. Clinicians need to educate patients before, during and after conception, emphasizing treatment compliance.

Overall, fecal markers have been found to be more accurate than serum markers. However, fecal markers are not specific for IBD and may be elevated in a range of organic conditions. Fecal calprotectin and lactoferrin can still differentiate inflammatory disease from functional bowel disorders. Comparison studies have found an overall diagnostic accuracy in IBD of 80% to 100% for both calprotectin and lactoferrin. Elevated levels are found in both CD and UC making it difficult to distinguish between these 2 diagnoses from these biomarkers alone. Both markers correlated well to mucosal healing and histologic improvement. Hence, they may be useful in monitoring response to treatment and predicting endoscopic and clinical relapse. Overall, patients with elevated markers were at higher risk of postoperative recurrence than those with normal levels. Fecal markers are useful in predicting pouchitis as well. Fecal markers are helpful as an adjunctive tool in overall evaluation of patients with nonspecific symptoms and as a management tool in those with inflammatory disease to monitor disease activity and possibility of relapse. They are less invasive than colonoscopy and can help guide management in a more cost-effective manner.

Physicians who care for patients of childbearing potential of both genders who require pelvic surgery must have a clear understanding of the best-available evidence with regards to infertility as an outcome in this cohort. More specifically, colorectal surgeons must clearly understand the ramifications of altered anatomy on fertility and be able to adequately counsel patients. In this article we provide definitions associated with fertility and review the best-available literature regarding the impact of medical therapy for inflammatory bowel disease on fertility and both female and male infertility after proctectomy for chronic ulcerative colitis and rectal cancer. Finally, we review techniques for optimization of fertility as well as available options and treatments for those who have difficulty conceiving.