Obesity/Bariatric Surgery and Crohn's Disease.

BACKGROUND: Crohn's disease (CD) following bariatric surgery has been previously described. It is not clear whether the clinical entity is due to rapid metabolism of fat, change in the bacterial milieu of the bowel, the loss of defense mechanisms of the stomach, or even a coincidence. OBJECTIVES: To present observations which might serve to sort out these various etiologies. DESIGN: We present 5 cases of colitis, ileocolitis or enteritis, some with fistula formation, with clinical onset following bariatric surgery and add these to the 7 cases previously identified as CD reported elsewhere. We provide the clinical features of these 12 cases to reconcile with causative mechanisms. LIMITATIONS: It remains possible that the onset of CD (or other inflammatory bowel disease) precedes the bariatric surgery which then accelerates the clinical manifestations described. Furthermore, without controls the association could remain a coincidence. CONCLUSIONS: We review the evidence for release of proinflammatory cells and cytokines contained in fat following the bariatric surgery, and also consider the roles that the surgical resection of stomach and shortening of the bowel may also bring about this syndrome. The earlier onset is more likely due to surgical loss of defenses of the stomach and the later onset to a metabolic alteration of the presurgical obesity, involving fat metabolism, and/or the microbiome. The role of characteristic creeping fat of CD is also addressed.

Management of iatrogenic perforation during colonoscopy in ulcerative colitis patients: a survey of gastroenterologists and colorectal surgeons.

PURPOSE: Patients with ulcerative colitis, a high-risk group for the development of colon cancer, undergo colonoscopy more frequently than the general population. This increase in endoscopic evaluation also exposes these patients to an increased risk of complications, including iatrogenic perforation. Our survey study aims to determine factors that affect the management choices for iatrogenic perforations for ulcerative colitis patients in remission and identify areas of consensus among general gastroenterologists, inflammatory bowel disease specialists, and colorectal surgeons. METHODS: An anonymous, cross-sectional survey was performed using an online platform. A matrix questionnaire posed five clinical scenarios with six management options for an iatrogenic perforation in ulcerative colitis patients with varying disease distribution, disease activity, and maintenance regimens. RESULTS: One hundred thirty-eight general gastroenterologists, 35 inflammatory bowel disease specialists, and 174 colorectal surgeons responded to the survey; 47, 41, and 23%, respectively, answered they did not feel comfortable managing perforations in ulcerative colitis patients in remission. We found the greatest concordance among gastroenterologists and colorectal surgeons in cases of perforation in ulcerative colitis with a history of dysplasia; the majority of respondents chose staged total proctocolectomy with ileal pouch anal anastomosis. We found discordance in decision making for ulcerative colitis in remission without dysplasia, with perforation occurring in colitis involved and uninvolved areas. CONCLUSION: Our survey revealed that a significant fraction of gastroenterologists and colorectal surgeons are uncomfortable managing iatrogenic colonic perforations in ulcerative colitis patients. We have identified knowledge and practice gaps in defining the optimal management of iatrogenic perforations in ulcerative colitis patients.

High Incidence of Recurrent Crohn's Disease Following Colectomy for Ulcerative Colitis Revealed with Long Follow-Up.

BACKGROUND AND AIMS: Ulcerative colitis (UC) patients with progression of their disease despite optimized medical therapy may warrant "curative" proctocolectomy with end ileostomy or ileo-anal pouch (IPAA) anastomosis. The aim of our study was to assess the incidence of later recurrent ileitis that lead to altering the initial diagnosis to Crohn's disease (CD). METHODS: A retrospective analysis was conducted on the inflammatory bowel disease database at Lenox Hill Hospital. The database consisted of patients that were diagnosed with UC or CD based on clinical assessment, endoscopic appearance, gross and histological examination, and imaging between 1960 and 2015. The post-colectomy follow-up period was at least 10 years. Recurrent disease was classified by evidence of transmural inflammation in the distal ileum, fistulizing disease, or stricturing disease. RESULTS: From our IBD database, we identified 128 patients who underwent elective or urgent colectomy with the preoperative diagnosis of UC. Thirty-two (25%) had either an IPAA or end ileostomy with documented recurrence of inflammation in the small bowel mucosa consistent with CD. There was no significant difference between the type of surgical approach and the chance of recurrent disease (p = .20). The average time to clinically significant recurrence was 5 years. CONCLUSION: The incidence of recurrent CD following colectomy for ulcerative colitis, when followed postoperatively for an average of 20 years, was 25%, considerably more than previously reported. Patients who come to colectomy for ulcerative colitis and are followed for at least 10 years show a high incidence of recurrent Crohn's disease in the ileostomy or ileo-anal pouch. Extended follow-up should be included in patients coming to colectomy for ulcerative colitis before they should be considered cured of their disease.

Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND: Approximately 15-20% of ulcerative colitis patients and 20-40% of those with Crohn's disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. AIMS: This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. METHODS: We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. RESULTS: Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn's disease. CONCLUSIONS: These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

Sequential Crohn's Ileitis, Ileosigmoidal Fistula, Segmental Sigmoid Polyposis, and Sigmoid Stricture: The Natural History.

BACKGROUND: We have previously recognized segmental sigmoid polyps as an indicator of a fistula from Crohn's ileitis to the sigmoid or the proximal rectum. In the course of this study, we realized that many patients with this fistula had no sigmoid polyps, but the sigmoid was the site of marked inflammation and early or late stricture formation. Furthermore, in some patients with a stricture, the fistula was not recognized until the surgeon (or the pathologist) dissected an inflammatory peri-ileal and/or a perisigmoidal mass.In this study, we have sought to clarify the sequence of events by focusing on the segmental inflammation and the stricturing of the sigmoid so that its significance can be recognized as a local complication of the ileitis and the progression of its severity as opposed to arising sui generis. MATERIALS AND METHODS: From our database of >3000 patients with inflammatory bowel disease at Lenox Hill Hospital, we identified 45 patients with Crohn's ileitis and ileosigmoid fistula (ISF): 24 had segmental sigmoid polyps and 18 had segmental inflammatory sigmoid strictures. The fistula was first seen by imaging in 36 patients, but not until resection by the surgeon or dissection by the pathologist in 7 patients. RESULTS: The method of diagnosis for the initial recognition of the ISF and the sigmoid stricture is presented in Table 1. In 36 of the 45 cases, the ISF was recognized by radiologic imaging. In total, 31 of the 36 cases required surgical intervention, not because of the fistula, but because of small-bowel obstruction due to the ileitis. In 7 of the 31 (22%) cases, the fistula was recognized only by dissection of the inflammatory ileosigmoid mass by the surgeon or examination of the surgical specimen by the pathologist. The sequence of events from the originating ileitis to the ISF to the segmental sigmoid polyposis and stricture, with the resulting sigmoid obstruction, is shown in Figures 1A-E. CONCLUSIONS: We emphasize the natural history of the ISF so that its recognition will lead to earlier medical management of the originating ileitis. Furthermore, it adds evidence of the recognition that the causative agent of Crohn's disease is carried by the fecal stream.

Risk of New or Recurrent Cancer in Patients With Inflammatory Bowel Disease and Previous Cancer Exposed to Immunosuppressive and Anti-Tumor Necrosis Factor Agents.

BACKGROUND & AIMS: Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. METHODS: We performed a retrospective analysis of data from 333 patients with IBD treated at 8 academic medical centers who developed cancer and subsequently received treatment with anti-tumor necrosis factor (TNF), anti-TNF with an antimetabolite (thiopurines, methotrexate), antimetabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated by using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared by using the log-rank test. RESULTS: During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible because of the relatively small sample sizes. There was no difference in time to incident cancer (P = .14) or type of incident cancer (P = .61) among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF, 0.32; 95% confidence interval [CI], 0.09-1.09; HR for anti-TNF with an antimetabolite, 0.64; 95% CI, 0.26-1.59; HR for an antimetabolite, 1.08; 95% CI, 0.54-2.15) or time to subsequent cancer between study arms (P = .22). CONCLUSION: On the basis of a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an antimetabolite after cancer was not associated with an increased risk of incident cancer, compared with patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.

Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases.

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.

Evaluation of 22 genetic variants with Crohn's disease risk in the Ashkenazi Jewish population: a case-control study.

BACKGROUND: Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population. METHODS: We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value. RESULTS: Three NOD2 SNPs, two IL23R SNPs, and one SNP each at IRGM and PTGER4 were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16). CONCLUSIONS: CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.

The Changing Prognosis of Ulcerative Colitis and Crohn Disease by Decades.

We present a bird's eye view of the prognosis for both ulcerative colitis and Crohn disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications, and deaths by decades.

Corticosteroid and Biologic Use Not Associated With Adverse Outcomes for Inflammatory Bowel Disease Patients Hospitalized With COVID-19.

BACKGROUND: To date, studies investigating the inflammatory bowel disease (IBD) patient experience with coronavirus disease 2019 (COVID-19) have consistently reported that the observed rate of COVID-19 within this population is similar to the general population. Limited research has suggested that corticosteroid use in the IBD population may be associated with worse COVID-19 outcomes, but it is still yet to be determined if specific IBD-related clinical factors are associated with worse outcomes. Our goal was to describe clinical COVID-19 outcomes for IBD patients and to identify the clinical factors that may be associated with worse outcomes. METHODS: In this retrospective study, we utilized the inpatient database within the largest hospital network in the New York City Metropolitan area to identify all IBD patients with confirmed COVID-19. RESULTS: Of 83 IBD/COVID-19 patients presenting to a hospital network emergency room, 56 were hospitalized. Overall, 19.6% of hospitalized IBD patients died, compared with 22.2% of all hospital system COVID-19 patients during the time period. There was no association between pre-admission corticosteroid use or biologic treatment with a severe course of COVID-19. CONCLUSIONS: In contrast to some prior reports, we did not observe an association of pre-admission corticosteroid use and adverse outcomes. While the mortality rate was high for IBD/COVID-19 patients, it was not greater than that for hospitalized COVID-19 patients generally. Though our results are encouraging, we continue to support the recommendations of the leading gastrointestinal and IBD societies to regard our patients as "at risk", and to observe caution in their care.

Rectal strictures in Crohn's disease and coexisting perirectal complications.

BACKGROUND: The significance of the presence of rectal strictures in Crohn's disease has not been well studied. The aim of this study was to examine patients diagnosed with Crohn's disease associated with rectal strictures and to describe co-existing manifestations of perianal disease (abscesses, fistulae, or skin tags) and strictures located elsewhere in the colon or small intestine. METHODS: A cohort of 70 Crohn's disease patients with rectal strictures were compared with controls without rectal strictures matched for age, gender, and duration of disease. Analysis was done to better elucidate the association of rectal strictures with location of disease and other perirectal complications. RESULTS: The average age of both groups of our Crohn's disease patients was 54 years and the average duration of disease since diagnosis was 315 months for the patients and 314 months for the controls. 54% of patients were women and 46% were men. 61.4% of the study population had Crohn's colitis, whereas the remaining 38.6% of patients had ileo-colonic involvement. In contrast, the majority of the control population had ileo-colonic involvement (74.3%). Perirectal fistulae were present in 61% of patients with rectal strictures versus 34.3% of controls (p value = 0.001). Perirectal abscesses were present in 50% of rectal stricture patients vs. 17.1% of controls (p value < 0.001). Anal skin tags were observed in 23% of study patients vs. 15.7% of controls (p value = 0.275). 37% of patients with rectal strictures also had strictures more proximal in the colon as compared to 54% of controls (p value = 0.07). Only 10% of the study population had small bowel strictures vs. 55.7% of the controls (p value < 0.001). CONCLUSIONS: This observational study of Crohn's disease patients suggests that the majority of patients with rectal strictures have colonic involvement and increased perianal fistulae and abscesses. Only a minority of patients was observed to have ileal or ileo-colonic disease, perianal skin tags, or strictures elsewhere. A future study will examine whether the severity of stricturing disease can tell us anything about the disease distribution, prognosis, or response to treatment. Patients with rectal strictures and associated perirectal disease may represent a specific phenotypic presentation of Crohn's disease that warrants further study and correlation with serological markers so as to better aid this subgroup of patients.

Increasing Pediatricians' Awareness of the Association between Anal Skin Tags and Earlier Diagnosis of Crohn's Disease.

OBJECTIVE: To seek the habits of pediatricians by which anorectal skin tags (AST) of Crohn's disease might be overlooked. METHODS: Questionnaires were sent to pediatricians affiliated with the Northwell Health System. RESULTS: Based on the responses, the majority of pediatricians did feel the abdomen of children presenting with abdominal pain or diarrhea but did not spread the buttocks to seek the presence of AST unless there was rectal pain, rectal bleeding, or, in some cases, loose stools. CONCLUSIONS: The diagnosis of Crohn's disease could be made earlier when asymptomatic AST are searched for in children with gastrointestinal symptoms.

Choice of laxatives and colonoscopic preparation in pregnant patients from the viewpoint of obstetricians and gastroenterologists.

AIM: To elucidate the preferences of gastroenterologists at our institution and compare them to those of obstetricians when making decisions in the pregnant patient, including which type of bowel preparations to use for flexible sigmoidoscopy or colonoscopy, as well as which laxatives can be used safely. METHODS: Surveys were mailed to all attending gastroenterologists (n = 53) and obstetricians (n = 99) at our institution. Each survey consisted of the 14 most common laxative or motility agents used in pregnancy and inquired about the physician's prescribing habits in the past as well as their willingness to prescribe each medication in the future. The survey also listed four common bowel preparations used prior to colonoscopy and sigmoidoscopy and asked the physician to rank the order of the preferred agent in each case. RESULTS: With regard to common laxatives, both gastroenterologists and obstetricians favor the use of Metamucil, Colace, and Citrucel. Both groups appear to refrain from using Fleets Phosphosoda and Castor oil. Of note, obstetricians are less inclined to use PEG solution and Miralax, which is not the case with gastroenterologists. In terms of comparing bowel preparations for colonoscopy, 50% of gastroenterologists prefer to use PEG solution and 50% avoid the use of Fleets Phosphosoda. Obstetricians seem to prefer Fleets Phosphosoda (20%) and tend to avoid the use of PEG solution (26%). With regard to bowel preparation for sigmoidoscopy, both groups prefer Fleets enema the most (51%), while magnesium citrate is used least often (38%). CONCLUSION: It is clear that preferences in the use of bowel cleansing preparations between the two groups exist, but there have not been many case controlled human studies in the pregnant patient that give clear cut indications for using one versus another drug. In light of the challenge of performing controlled trials in pregnant women, more extensive surveys should be undertaken to gather a larger amount of data on physician's experiences and individual preferences.

Abnormalities of uterine cervix in women with inflammatory bowel disease.

AIM: To evaluate the prevalence of abnormalities of the uterine cervix in women with inflammatory bowel disease (IBD) when compared to healthy controls. METHODS: One hundred and sixteen patients with IBD [64 with Crohn's disease (CD) and 52 with ulcerative colitis (UC)] were matched to 116 healthy controls by age (+/- 2 years) at the time of most recent papanicolaou (Pap) smear. Data collected consisted of age, race, marital status, number of pregnancies, abortions/miscarriages, duration and severity of IBD, Pap smear results within five years of enrollment, and treatment with immunosuppressive drugs. Pap smear results were categorized as normal or abnormal including atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LGSIL), and high-grade squamous intraepithelial lesion (HGSIL). RESULTS: The median age at the time of Pap smear was 46 (range: 17-74) years for the IBD group and matched controls (range: 19-72 years). There were more Caucasian subjects than other ethnicities in the IBD patient group (P = 0.025), as well as fewer abortions (P = 0.008), but there was no significant difference regarding marital status. Eighteen percent of IBD patients had abnormal Pap smears compared to 5% of controls (P = 0.004). Subgroup analysis of the IBD patients revealed no significant differences between CD and UC patients in age, ethnicity, marital status, number of abortions, disease severity, family history of IBD, or disease duration. No significant difference was observed in the number of abnormal Pap smears or the use of immunosuppressive medications between CD and UC patients (P = 0.793). No definitive observation could be made regarding HPV status, as this was not routinely investigated during the timeframe of our study. CONCLUSION: Diagnosis of IBD in women is related to an increased risk of abnormal Pap smear, while type of IBD and exposure to immunosuppressive medications are not. This has significant implications for women with IBD in that Pap smear screening protocols should be conscientiously followed, with appropriate investigation of abnormal results.

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective.

The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.