Amy L. Lightner

Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Abdominal Operations for Inflammatory Bowel Disease

Introduction: Vedolizumab was recently approved by the Food and Drug Administration for the treatment of moderate to severe ulcerative colitis [UC] and Crohn’s disease [CD]. No study to date has examined the rate of postoperative infectious complications among patients who received vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among inflammatory bowel disease [IBD] patients who received vedolizumab within 12 weeks of an abdominal operation as compared to patients who received tumour necrosis factor &agr; [TNF&agr;] inhibitors or no biological therapy. Methods: A retrospective chart review between May 1, 2014 and December 31, 2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort comprised patients who received vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNF&agr; inhibitors or no biological therapy. Results: In total, 94 patients received vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications [53%], 35 of which were surgical site infections [SSIs] [36%]. The vedolizumab group experienced significantly higher rates of any postoperative infection [53% vs 33% anti-TNF and 28% non-biologics; p<0.001] and SSI [37% vs 10% and 13%; p<0.001]. On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative SSI [p<0.001]. Conclusions: Thirty-seven per cent of IBD patients who received vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNF&agr; inhibitors or no biological therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis.

Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for Treatment of Perianal Fistulas in Patients With Crohn's Disease

In patients with Crohns disease, perianal fistulas recur frequently, causing substantial morbidity. We performed a 12-patient, 6-month, phase 1 trial to determine whether autologous mesenchymal stem cells, applied in a bioabsorbable matrix, can heal the fistula. Fistula repair was not associated with any serious adverse events related to mesenchymal stem cells or plug placement. At 6 months, 10 of 12 patients (83%) had complete clinical healing and radiographic markers of response. We found placement of mesenchymal stem cell-coated matrix fistula plugs in 12 patients with chronic perianal fistulas to be safe and lead to clinical healing and radiographic response in 10 patients. ClinicalTrials.gov Identifier: NCT01915927.

Results at Up to 30 Years After Ileal Pouch–Anal Anastomosis for Chronic Ulcerative Colitis

Background: Ileal pouch–anal anastomosis (IPAA) has become the surgical procedure of choice for patients with chronic ulcerative colitis. No study to date has examined functional and quality-of-life outcomes 30 years after pouch construction. Methods: Using data from a prospectively maintained database with annually distributed questionnaires, functional outcomes, pouch complications, and quality of life after IPAA were determined. Results: Overall, 93.3% of patients had a functioning pouch at 30 years. Stool frequency during the day increased slightly from a mean of 5.7 (SD, 2.3) at 1 year to 6.2 (SD, 2.9) at 30 years (P < 0.001); nighttime frequency also increased slightly from 1.5 (SD, 1.2) to 2.1 (SD, 1.2) (P < 0.001). Pouch outcomes and stool frequency were significantly associated with diagnosis, being worse in patients with Crohns disease, but were minimally associated with age greater than 65 years. After IPAA, the 30-year cumulative probability of pouchitis, stricture, obstruction, and fistula were 80.2%, 56.7%, 44.0%, and 15.8%, respectively. Quality of life scores remained stable over the 30 years. Conclusions: IPAA is a durable operation for patients requiring proctocolectomy for chronic ulcerative colitis and indeterminate colitis. The functional outcomes and quality of life remained relatively unchanged over the 30 years after IPAA underscoring the longevity of pouches.

Crohn's Disease of the Ileoanal Pouch.

Abstract:Crohns disease (CD) of the pouch is an increasingly recognized diagnosis after ileal pouch-anal anastomosis. This post–ileal pouch-anal anastomosis diagnosis in conjunction with pouchitis remains the leading reason for pouch excision. Unfortunately, CD of the pouch remains a difficult diagnosis with lack of a uniform definition largely because of its similarity to common postoperative pouch complications, including pouchitis, abscess formation, or stricture at the anastomosis. Once diagnosed, treatment algorithms largely include multimodal therapy including biologics. This review focuses on the definition, etiology, diagnosis, and treatment for CD of the pouch, a postoperative de novo diagnosis of CD.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations

Up to 80% of patients with Crohns disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohns disease, it is important to understand its potential association with post‐operative complications.

Crohn's Disease of the Pouch: A True Diagnosis or an Oversubscribed Diagnosis of Exclusion?

BACKGROUND: After IPAA, 8% of patients with ulcerative colitis are later diagnosed with Crohn’s disease of the pouch, associated with an increased rate of pouch failure. No study has reported on how often the clinical diagnosis is correlated with histologic findings of Crohn’s disease in the excised pouch. OBJECTIVE: The purpose of this study was to determine whether the clinical diagnosis is consistent with pathologic confirmation at pouch excision. SETTINGS: The study was conducted at a tertiary IBD referral center. PATIENTS: Patients with chronic ulcerative colitis who underwent pouch excision for presumed Crohn’s disease of the pouch were included. MAIN OUTCOME MEASURES: Preoperative evaluation and pathologic variables at the time of pouch excision were measured. RESULTS: A total of 35 patients underwent pouch excision for Crohn’s disease of the pouch based on a combination of clinical, radiographic, and endoscopic findings. Seven (20%) had surgical pathology consistent with Crohn’s disease at pouch excision. There were no differences in those 7 patients and the remaining 28 in terms of diagnosis at colectomy, primary pouch symptoms, prepouch inflammation, ulceration, or granulomas at endoscopy. In the nonpathology-confirmed Crohn’s disease, 40% (n = 11) had an anastomotic leak at time of IPAA versus 0% in the Crohn’s disease group, and 86% (n = 24) had symptoms of pouch dysfunction within 5 months of ileostomy reversal versus 13 months in the Crohn’s disease group. Of 28 without pathology-confirmed Crohn’s disease, 100% (n = 28) were treated with antibiotics, 68% (n = 19) with steroids, 59% (n = 16) with immunomodulators, and 57% (n = 15) with biologic therapy for Crohn’s disease of the pouch. LIMITATIONS: The study was limited by its single-center scope and lack of an established definition for Crohn’s disease of the pouch. CONCLUSIONS: Pathologic confirmation of Crohn’s disease was given to only one fifth of patients who underwent pouch excision for Crohn’s disease of the pouch. Given the histologic variability in Crohn’s disease, it may be unreasonable to expect histologic confirmation in every case; still, the diagnosis of Crohn’s disease of the pouch may be overly ascribed, resulting in unnecessary immunosuppressive medications and exclusion from consideration for pouch reconstructive surgery. See Video Abstract at http://links.lww.com/DCRA432.

Nonrelaxing Pelvic Floor Dysfunction Is an Underestimated Complication of Ileal Pouch–Anal Anastomosis

Background & Aims Nonrelaxing pelvic floor dysfunction (N‐RPFD), or dyssynergic defecation, is the paradoxical contraction and/or impaired relaxation of pelvic floor and anal muscles during defecation. Few studies have evaluated this disorder in patients with an ileal pouch–anal anastomosis (IPAA). We investigated the frequency of N‐RPFD in patients with and without chronic pouchitis following IPAA and the effectiveness of biofeedback therapy within this population. Methods We conducted a retrospective study of all patients with an IPAA who underwent anorectal manometry between January 2000 and March 2015 (n = 111). N‐RPFD was diagnosed in patients with symptoms consistent with a pouch evacuation disorder and 1 or more of the following abnormal tests: anorectal manometry, balloon expulsion test, barium or magnetic resonance defecography, or external anal sphincter electromyography. Patients who completed biofeedback therapy were identified and assessed to determine symptomatic response. Results Of the 111 patients evaluated, 83 (74.8%) met criteria for N‐RPFD. A significantly higher proportion of patients with chronic pouchitis were diagnosed with N‐RPFD than patients without chronic pouchitis (83.3% vs 62.2%, respectively; P = .012). Most patients diagnosed with N‐RPFD had abnormal results from the balloon expulsion test (78.3%); 53.0% of patients diagnosed with N‐RPFD had abnormal findings from external anal sphincter electromyography, 25.3% had abnormal defecography findings, and 20.5% had abnormal findings from anorectal manometry. Twenty‐two patients completed biofeedback therapy: 15 patients (68.2%) had mild–moderate improvement and 5 patients (22.7%) had significant improvement of symptoms. Conclusions N‐RPFD occurs in almost 75% of patients with an IPAA, especially in patients with chronic pouchitis. Biofeedback seems to be an effective therapy for patients with an IPAA and N‐RPFD, but further studies are needed for validation.

Postoperative Outcomes in Ustekinumab-Treated Patients Undergoing Abdominal Operations for Crohn’s Disease

Background Ustekinumab, a monoclonal antibody targeting interleukins-12 and -23 is used to treat adults with Crohns disease [CD]. We determined the 30-day postoperative infectious complication rate among CD patients who received ustekinumab within the 12 weeks prior to an abdominal operation as compared with patients who received anti-tumor necrosis factor [TNF] agents. Methods A retrospective chart review of adults with CD who underwent an abdominal operation between January 1, 2015 and May 1, 2017 was performed across six sites. Surgical site infection [SSI] was defined as superficial skin and soft tissue infection, intra-abdominal abscess, anastomotic leak, and mucocutaneous separation of the stoma. Results Forty-four patients received ustekinumab and 169 patients received anti-TNF therapy within the 12 weeks prior to surgery. The two groups were similar, except anti-TNF patients were more likely to have received combination therapy with an immunomodulator [P = 0.006]. There were no significant differences in postoperative SSI [13% in ustekinumab versus 20% in anti TNF-treated patients, p = 0.61] or hospital readmission rates [18% versus 10%, respectively, p = 0.14], but ustekinumab-treated patients had a higher rate of return to the operating room [16% versus 5%; P = 0.01]. There were no significant predictors identified on multivariable analysis. Conclusions Of the 44 patients with CD who received ustekinumab within the 12 weeks prior to a major abdominal operation, 13% experienced a 30-day postoperative SSI, not statistically different from the 20% found in the anti-TNF cohort. Ustekinumab treatment within 12 weeks of surgery does not appear to increase the risk of postoperative SSI above that of CD patients treated with anti-TNF medications.

Systematic Review and Meta-Analysis: Preoperative Vedolizumab Treatment and Postoperative Complications in Patients with Inflammatory Bowel Disease

Background and Aims The impact of vedolizumab, a gut-selective monoclonal antibody, on postoperative outcomes is unclear. This study aimed to assess the impact of preoperative vedolizumab treatment on the rate of postoperative complications in patients with inflammatory bowel disease [IBD] undergoing abdominal surgery. Methods A systematic search of multiple electronic databases from inception until May 2017 identified studies reporting rates of postoperative complications in vedolizumab-treated IBD patients compared to no biologic exposure or anti-tumor necrosis factor (anti-TNF) treated IBD patients. Outcomes of interest included postoperative infectious complications and overall postoperative complications. Pooled risk ratios and 95% confidence intervals were estimated using the random-effects model. Results Five studies comprising 307 vedolizumab-treated IBD patients, 490 anti-TNF-treated IBD patients and 535 IBD patients not exposed to preoperative biologic therapy were included. The risk of postoperative infectious complications (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.37-2.65) and overall postoperative complications [RR 1.00, 95% CI 0.46-2.15] were not significantly different between vedolizumab-treated patients and those who received no preoperative biologic therapy. In addition, the risk of postoperative infectious complications [RR 0.99, 95% CI 0.34-2.90] and overall postoperative complications [RR 0.92, 95% CI 0.44-1.92] were not significantly different between vedolizumab-treated vs anti-TNF-treated patients. Conclusions Preoperative vedolizumab treatment in IBD patients does not appear to be associated with an increased risk of postoperative infectious or overall postoperative complications compared to either preoperative anti-TNF therapy or no biologic therapy. Future prospective studies which include perioperative drug level monitoring are needed to confirm these findings.

Mesenchymal Stem Cell Injections for the Treatment of Perianal Crohn’s Disease: What We Have Accomplished and What We Still Need to Do

Perianal Crohns disease [CD] is found in a quarter of patients with CD and remains notoriously difficult to treat. Several medical and surgical therapies are available. However, none is particularly effective nor reliably provides sustained remission. In addition, surgical intervention is complicated by poor healing and the potential for incontinence. Mesenchymal stem cell-based therapies provide a promising treatment alternative for perianal CD, with demonstrated safety, improved efficacy, and a decreased side effect profile. Several phase I, II, and now III randomised controlled trials have now reported safety and efficacy in treating perianal CD. The aim of this review is to discusses the outcomes of conventional treatment approaches, outcomes of mesenchymal stem cell therapies, considerations specific to stem cell-based therapies, and future directions for research.