Faculty Bibliography

BACKGROUND/UNASSIGNED:Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited. METHODS/UNASSIGNED:We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. RESULTS/UNASSIGNED:Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. CONCLUSIONS/UNASSIGNED:In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population.

BACKGROUND:Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). METHODS:We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). RESULTS:We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. CONCLUSION/CONCLUSIONS:Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

Pouchoscopy provides a critical objective measure in the evaluation of patients with suspected inflammatory conditions of the pouch; however, there remain significant gaps in the reliability of the endoscopic scales used in the assessment of these conditions.^1,2 Reliability and reproducibility in the assessment of patients after ileal pouch-anal anastomosis (IPAA) are critical, as evidenced by recent efforts to improve standardization in the evaluation of patients with pouch-related disorders.³.

OBJECTIVE:We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS:This study utilized a retrospective, multicenter, multinational, consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission were assessed using time-to-event and clinical predictors were assessed by multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS:A total of 1113 patients (51.8% female, 90% prior anti-TNF exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naïve patients achieved significantly higher rates of clinical and endoscopic remission at 63% and 55%, respectively. On multivariable analyses, prior anti-TNF (HR, 0.72; 95% CI, 0.49-0.99) and vedolizumab exposure (HR, 0.65; 95% CI, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77/102 (75%) underwent dose optimization, and 44/77 (57%) achieved clinical response. An additional 152/681 (22.3%) patients were dose optimized as a result of primary non- or incomplete response to UST, of whom 40.1% (61/152) responded. Serious infections occurred in 3.4% of patients, while other non-infectious adverse events [lymphoma (n=1), arthralgia (n=6), rash (n=6), headache (n=3), hepatitis (n=3), hair loss (n=3), neuropathy (n=1), and vasculitis (n=1)] occurred in 2.4% of patients. CONCLUSIONS:UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in bio-naive patients, and dose escalation may recapture clinical response.

Functional anorectal disorders are common in patients with ileal pouch-anal anastomosis (IPAA) and often have a debilitating impact on quality of life. The diagnosis of functional anorectal disorders, including fecal incontinence (FI) and defecatory disorders, requires a combination of clinical symptoms and functional testing. Symptoms are generally underdiagnosed and underreported. Commonly utilized tests include anorectal manometry, balloon expulsion test, defecography, electromyography, and pouchoscopy. The treatment for FI begins with lifestyle modifications and medications. Sacral nerve stimulation and tibial nerve stimulation have been trialed on patients with IPAA and FI, resulting in improvement in symptoms. Biofeedback therapy has also been used in patients with FI but is more commonly utilized in defecatory disorders. Early diagnosis of functional anorectal disorders is important because a response to treatment may significantly improve a patient's quality of life. To date, there is limited literature describing the diagnosis and treatment of functional anorectal disorders in patients with IPAA. This article focuses on the clinical presentation, diagnosis, and treatment of FI and defecatory disorders in patients with IPAA.

Functional anorectal disorders are common in patients with ileal pouch-anal anastomosis (IPAA) and often have a debilitating impact on quality of life. The diagnosis of functional anorectal disorders, including fecal incontinence (FI) and defecatory disorders, requires a combination of clinical symptoms and functional testing. Symptoms are generally underdiagnosed and underreported. Commonly utilized tests include anorectal manometry, balloon expulsion test, defecography, electromyography, and pouchoscopy. The treatment for FI begins with lifestyle modifications and medications. Sacral nerve stimulation and tibial nerve stimulation have been trialed on patients with IPAA and FI, resulting in improvement in symptoms. Biofeedback therapy has also been used in patients with FI but is more commonly utilized in defecatory disorders. Early diagnosis of functional anorectal disorders is important because a response to treatment may significantly improve a patient's quality of life. To date, there is limited literature describing the diagnosis and treatment of functional anorectal disorders in patients with IPAA. This article focuses on the clinical presentation, diagnosis, and treatment of FI and defecatory disorders in patients with IPAA.

BACKGROUND:There is little data regarding the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a prior history of cancer who are exposed to ustekinumab or vedolizumab. We assessed the risk of subsequent cancer in patients exposed to these agents. METHODS:We performed a retrospective cohort study of patients with IBD and a history of cancer at an academic medical center between January 2013 and December 2020. We collected data on demographics, IBD and cancer disease characteristics, and drug exposures. The primary exposure was immunosuppressive therapy after diagnosis of cancer. The primary outcome was interval development of new or recurrent cancer. RESULTS:Of 390 patients with IBD and a previous history of cancer, 37 were exposed to vedolizumab, 14 ustekinumab, 41 antitumor necrosis factor (anti-TNF), and 31 immunomodulator; and 267 were not exposed to immunosuppression following cancer diagnosis. During a total median follow-up time of 52 months, 81 (20%) patients developed subsequent cancer: 6 (16%) were exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to immunomodulators, 12 (29%) to anti-TNF, and 56 (21%) with no immunosuppression (P = .41). In a multivariable Cox model adjusting for age, IBD subtype, smoking, cancer recurrence risk, and cancer stage, there was no increase in subsequent cancer with vedolizumab (adjusted hazard ratio, 1.36; 95% CI, 0.27-7.01) or ustekinumab (adjusted hazard ratio, 0.96; 95% CI, 0.17-5.41). Patients with more than 1 biologic exposure also did not have an increased risk of subsequent cancer. CONCLUSIONS:Exposure to ustekinumab or vedolizumab in patients with IBD and a prior history of cancer does not appear to be associated with an increased risk of subsequent new or recurrent cancer.

PURPOSE/OBJECTIVE:To compare terminal ileum (TI) mucosal iodine density obtained at dual-energy CT enterography (DECTE) with conventional CT interpretation and endoscopy in patients with Crohn's disease (CD). MATERIALS AND METHODS/METHODS:) from the distal 2 cm ileum (TI) mucosa obtained using semiautomatic prototype software were compared with endoscopic assessment using Mann Whitney tests. The optimal threshold I% and I were determined from receiver operating curves (ROC). Sensitivity and specificity of conventional interpretation and determined iodine thresholds were compared using McNemar's test. Inter-reader agreement was assessed using kappa. A p < 0.05 indicated statistical significance. RESULTS:was similar for patients with and without endoscopic active inflammation (0.82[0.33]mg/mL and 0.77[0.28]mg/mL, respectively, p = 0.37). Conventional interpretation sensitivity and specificity (R1/R2) were 83.3%/91.7% and 72.7%/54.5%, respectively (all p > 0.05) with moderate inter-reader agreement (Κ = 0.542[95% CI 0.0202-0.088]). CONCLUSION/CONCLUSIONS:Mean normalized iodine density is highly sensitive and specific for endoscopic active inflammation. DECTE could be considered as a surrogate to endoscopy in CD patients. Despite trends towards improved sensitivity and specificity compared with conventional interpretation, future larger studies are needed.

Introduction: Up to 80% of patients will develop pouchitis after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, and approximately 10% will develop Crohn's disease (CD) of the pouch. We designed a geographically diverse, eight-center, prospective registry to study the disease course among patients with one of four inflammatory conditions of the pouch. The aim of this study was to evaluate patterns of changes in diagnosis during the first 12 months after enrollment.
Method(s): We enrolled patients with a confirmed diagnosis of acute pouchitis, chronic antibiotic dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or CD of the pouch. Diagnoses were based on standardized criteria and we obtained detailed clinical and demographic data at the time of enrollment. Patients completed follow-up assessments at 3, 6, and 12 months after enrollment, with treating physicians confirming their respective diagnoses at each time point. Associations between clinical and demographic data at baseline and a switch in diagnosis to a more refractory disease state were analyzed using chi-square testing.
Result(s): We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). During the first 12 months after enrollment, 31 of the 157 patients (20%) without CD of the pouch at enrollment switched diagnosis to a more refractory disease state, with 20 of 31 (65%) patients ultimately being diagnosed with CD of the pouch. Among 7 patients with acute pouchitis who switched diagnoses, 5 were diagnosed with CADP, 1 with CARP, and 1 with CD of the pouch. Among 19 patients with CADP who switched diagnoses, 4 were diagnosed with CARP and 15 were diagnosed with CD of the pouch. Four patients with CARP had a change in diagnosis to CD of the pouch during the study period. Patients who experienced a change in diagnosis were significantly more likely to be current smokers when compared to patients with no change in diagnosis during the study period (23% vs. 5%, p=0.001, Table).
Conclusion(s): In a prospective registry of 318 patients from eight centers in the United States, 20% of patients without CD of the pouch at enrollment experienced a change in diagnosis to a more refractory inflammatory condition of the pouch during the first 12 months after enrollment. Patients who were current smokers were more likely to change diagnoses, and may represent a high risk group for earlier intervention and targeted smoking cessation efforts after IPAA. (Table Presented)

PURPOSE/OBJECTIVE:To retrospectively evaluate which key imaging features described by SAR-AGA on outpatient surveillance MRE correlate with progression to surgery in adults with CD. METHODS:52 CD patients imaged with outpatient MRE from 10/2015 to 12/2016 and with available clinical information were included. Two abdominal radiologists reviewed the MRE for the presence of active inflammation, intramural edema, restricted diffusion, stricture, probable stricture, ulceration, sacculation, simple fistula, complex fistula, sinus tract, inflammatory mass, abscess, perienteric inflammation, engorged vasa recta, fibrofatty proliferation, and perianal disease. Bowel wall thickness, length of bowel involvement, and degree of upstream dilation in strictures were quantified. Subsequent bowel resection, prior bowel surgery, and available laboratory values were recorded. The association between progression to surgery and imaging features was evaluated using a logistic regression model adjusting for demographics, prior bowel surgery, medication usage, and body mass index. RESULTS:19.2% (10/52) of patients progressed to surgery. Restricted diffusion, greater degree of upstream dilation from stricture, complex fistula, perienteric inflammation, and fibrofatty proliferation were significantly more common in patients progressing to surgery (all p < 0.05). κ for these significant findings ranged 0.568-0.885. Patients progressing to surgery had longer length bowel involvement (p = 0.03). Platelet count, ESR, and fecal calprotectin were significantly higher, and serum albumin was significantly lower in patients progressing to surgery. Prior bowel surgery, sex, age, and all other parameters were similar. CONCLUSION/CONCLUSIONS:Radiologists should carefully describe bowel dilation upstream from strictures, penetrating and perienteric findings on outpatient MRE in CD patients, as these findings may herald progression to surgery.