Faculty Bibliography

INTRODUCTION: Previous studies have demonstrated that exposure to anti-TNFalpha and/or immunomodulators for inflammatory bowel disease (IBD) following a diagnosis of cancer was not associated with an increased risk of new or recurrent cancer. There is little data regarding the use of newer biologics, vedolizumab and ustekinumab, after a diagnosis of cancer. We aimed to investigate whether patients with IBD and a history of cancer who were subsequently exposed to vedolizumab or ustekinumab have an increased risk of developing new or recurrent cancer.
METHOD(S): We reviewed the medical records of 5062 patients with IBD and cancer from an academic medical center between January 2013 and November 2018 to identify IBD patients who received vedolizumab or ustekinumab following a diagnosis of cancer. We collected demographic, IBD and cancer-related data. Our primary outcome was the development of new or recurrent cancer. Results were compared to historical data regarding the risk of new or recurrent cancer in patients exposed to anti-TNFalpha, an immunomodulator or no therapy for IBD following a diagnosis of cancer.
RESULT(S): We identified IBD patients who received vedolizumab (n = 59) or ustekinumab (n = 18) monotherapy following a diagnosis of cancer (Table 1). The median age at cancer diagnosis was 51 years (IQR 43-65) for vedolizumab and 57 years (IQR 55-66) for ustekinumab. During a median follow-up of 68 months (IQR 21-132) for vedolizumab and 48 months (IQR 12-96) for ustekinumab, 3 (5%) and 3 (17%) patients developed subsequent cancer, respectively. Compared to historical data, there were differences in subsequent cancer risk between exposure groups (Figure 1; log-rank 0.001). However, when adjusted for stage of prior cancer, compared to no therapy, there was no difference in risk of new or recurrent cancer between patients exposed to vedolizumab (HR 0.01, 0.01-7.58), ustekinumab (HR 0.85, 0.11-6.50), anti-TNFalpha (HR 0.60, 0.34-1.07) or immunomodulators (HR 1.01, 0.58-1.75) following a diagnosis of cancer.
CONCLUSION(S): In this single-center study, exposure to vedolizumab or ustekinumab in patients with IBD and a history of cancer conferred a low risk of new or recurrent cancer. Exposure to vedolizumab or ustekinumab monotherapy was not associated with an increased risk of subsequent cancer compared to historical data of exposure to anti-TNF, immunomodulators or no immunosuppression following a diagnosis of cancer. Larger studies are needed to confirm these findings. (Figure Presented)

Background/Purpose : Prevalence of sacroiliitis (SI) in Crohn's disease (CD) varies widely (range 4% -39%), depending on criteria utilized to define the disease (e.g. inflammatory back pain, plain radiographs or MRI). Sacroiliitis may remain underdiagnosed in CD patients given lack of association with clinical symptoms of back pain and CD activity. However, patients with CD often undergo magnetic resonance enterography (MRE) to assess extent, severity of small bowel CD and radiographic healing, affording clinicians the opportunity to evaluate for the presence of active and/or chronic SI. We sought to identify the prevalence of sacroiliitis in CD patients utilizing MRE and determine its relationship with CD activity, especially with concurrent biologic therapy. Methods : All CD subjects undergoing MRE between years 2014-2018 at a large IBD referral center were identified. A musculoskeletal radiologist, blinded to clinical data, reviewed all MRE exams for the presence of acute bone marrow edema (BME) lesions and chronic lesions suggestive of acute and chronic SI, respectively. A second radiologist, also blinded, assessed MRE for mucosal CD activity using validated measures. Charts were reviewed for demographics, IBD characteristics, presence of back pain, clinical and endoscopic activity of CD, and Crohn's therapies within 3 months of MRE. Comparisons were made between CD subjects with and without SI using chi-square test. Univariate and multivariate logistic regression were used to determine risk factors of SI. Results : 258 subjects with CD underwent MRE during the study period with a mean age of 35 years old, 53% (n=138) were male, and mean duration of CD at the time of MRE was 9 years. Few reported back pain (8%) and 14% had previously seen a rheumatologist. Overall, 17% (n=45) of patients had MR evidence of sacroiliitis (Table 1). Female gender, presence of back pain, and later age of CD diagnosis were associated with signs of sacroiliitis (p=0.05, p< 0.001, p=0.04 respectively; Table 2). Stricturing phenotype was associated with a lower rate of SI (7% vs. 24%; p=0.018), but inflammatory or penetrating phenotypes were not. CD location, activity as noted by clinical scores, endoscopic disease activity, or radiographic disease activity on MRE, were not associated with sacroiliitis (Table 2). On multivariable analysis, back pain was associated with the presence of sacroiliitis on MRE (OR 3.0, 95% CI 1.1-5.6; p=0.04). Concurrent CD therapy with biologics did not lower the risk of sacroiliitis. Conclusion : Although often underdiagnosed, SI is a common comorbid condition in CD. While recent history of back pain was associated with the presence of sacroiliitis visualized on MRE, no correlations were found with other clinical and endoscopic markers of CD activity. Moreover, concurrent CD therapy, especially biologics, was not associated with a lower risk of sacroiliitis on MRE. With limited clinical clues and CD characteristics to suggest sacroiliitis, gastroenterologists can utilize MRE as a screening tool to detect SI and refer CD patients to rheumatologists. Presence of SI on MRE in CD patients with back pain may help identify a subset of individuals likely to benefit from switching to therapies with proven efficacy in axial SpA

BACKGROUND:Low socioeconomic status has been linked with numerous poor health outcomes, but data are limited regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by IBD patients based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status. METHODS:We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid with all other patients. RESULTS:Of 947 patients with IBD, 221 (23%) had been enrolled in Medicaid. Compared with patients with other insurance types, patients with Medicaid had higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, and ethnicity, patients with Medicaid had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59-3.36) and ED visits (RR 4.24; 95% CI 3.82-4.70) compared to patients with other insurance. Patients with Medicaid had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001), and after adjusting for the same factors, the odds of requiring steroids in the patients with Medicaid was increased (OR 3.77; 95% CI 2.53-5.62). CONCLUSIONS:Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often.

Crohn's disease and ulcerative colitis are chronic inflammatory diseases that lead to progressive bowel damage including the development of stricturing and penetrating complications. Increasingly, cross-sectional imaging with computed tomography or magnetic resonance scans have emerged as leading tools to: (1) assess disease activity; (2) monitor response to therapy or disease recurrence; and (3) identify disease-related complications. Several validated radiological scoring systems have been developed to quantify cross-sectional and longitudinal inflammatory burden in these diseases and to monitor response to treatment. Bowel ultrasound is also a simple and inexpensive tool but is operator dependent in its performance.

BACKGROUND: Low socioeconomic status has been linked to numerous poor health outcomes, but there is little data regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by patients with IBD based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status.
METHOD(S): We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid to all other patients.
RESULT(S): Of 947 patients with IBD, 221 (23%) ever had Medicaid. Compared to other insurances, Medicaid patients had significantly higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or ever visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, race, and ethnicity, Medicaid patients had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59-3.36) and ED visits (RR 4.24; 95% CI 3.82-4.70) compared to patients with other insurance. Medicaid patients had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001) and after adjusting for the same factors, the odds of requiring steroids in the Medicaid population was increased (OR 3.77; 95% CI 2.53-5.62). CONCLUSION(S): Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often

BACKGROUND & AIMS/OBJECTIVE:Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case-control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC). METHODS:Using the Swedish National Patient Register, we identified 44,214 patients with IBD (26,450 with UC; 13,387 with CD; and 4,377 with IBD-unclassified) from 2002 to 2014 and matched them with 436,507 individuals in the general population (controls). We then identified patients and controls with reported episodes of gastroenteritis (from 1964 to 2014) and type of pathogen associated. We collected medical and demographic data and used logistic regression to estimate odds ratios (ORs) for IBD associated with enteric infection. RESULTS:Of the patients with IBD, 3105 (7.0%) (1672 with UC, 1050 with CD, and 383 with IBD-unclassified) had a record of previous gastroenteritis compared with 17,685 controls (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR, 1.64; 1.57-1.71), bacterial gastrointestinal infection (aOR, 2.02; 1.82-2.24), parasitic gastrointestinal infection (aOR, 1.55; 1.03-2.33), and viral gastrointestinal infection (aOR, 1.55; 1.34-1.79). Patients with UC had higher odds of previous infection with Salmonella, Escherichia coli, Campylobacter, or Clostridium difficile compared to controls. Patients with CD had higher odds of previous infection with Salmonella, Campylobacter, Yersinia enterocolitica, Clostridium difficile, amoeba, or norovirus compared to controls. Increasing numbers of gastroenteritis episodes were associated with increased odds of IBD, and a previous episode of gastroenteritis was significant associated with odds for IBD more than 10 years later (aOR, 1.26; 1.19-1.33). CONCLUSION/CONCLUSIONS:In an analysis of the Swedish National Patient Register, we found previous episodes of gastroenteritis to increase odds of later development of IBD. Although we cannot formally exclude misclassification bias, enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals.

Background: Gastrointestinal bleeding (GIB)is a common complication of left ventricular assist device (LVAD)therapy. Previously, we retrospectively reviewed the endoscopic evaluation and outcomes of GIB in LVAD recipients in our center and proposed an endoscopic management algorithm (Figure)to eliminate low yield procedures. Herein, we aimed to prospectively validate this algorithm.
Method(s): We prospectively tested the algorithm in LVAD recipients who presented with GIB between June 2017 and August 2018. We compared the diagnostic and therapeutic yield of endoscopy, healthcare costs, and re-bleeding rates between conventional GIB management (our retrospective cohort)and our algorithm (our prospective cohort).
Result(s): Prospectively, we identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%)patients. In total, 41 endoscopies localized a source in 23 (56%)resulting in 14 (36%)interventions at a median LOS of 8 days. Of 18 lesions identified, AVMs were the most common (9, 50%)and the small bowel was the most common location (11, 48%). Despite non-adherence to the algorithm in 7 of 33 patients (21%), algorithm implementation in comparison to our retrospective cohort increased the diagnostic yield by 70% (p<0.01)and therapeutic yield by 125% (p=0.01), and reduced the number of procedures per patient by 24% (p<0.01), length of stay by 33% (p<0.01), and estimated costs by 18% (p<0.01). In assessing the safety of our algorithm, we found the same median number of packed red blood cell transfusions and observed no increase in re-bleeding events in the prospective cohort as compared to our retrospective cohort.
Conclusion(s): Our endoscopic management algorithm for GIB in LVAD patients was effective in reducing low yield endoscopic procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing healthcare resource utilization costs while not increasing the risk of re-bleeding. [Figure presented][Figure presented]
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OBJECTIVES/OBJECTIVE:Surveillance colonoscopy is thought to prevent colorectal cancer (CRC) in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim was to determine whether consecutive negative surveillance colonoscopies adequately predict low neoplastic risk. DESIGN/METHODS:A multicentre, multinational database of patients with long-standing IBD colitis without high-risk features and undergoing regular CRC surveillance was constructed. A 'negative' surveillance colonoscopy was predefined as a technically adequate procedure having no postinflammatory polyps, no strictures, no endoscopic disease activity and no evidence of neoplasia; a 'positive' colonoscopy was a technically adequate procedure that included at least one of these criteria. The primary endpoint was advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia or CRC. RESULTS:1 positive colonoscopy on follow-up of 6.1 (P25-P75: 4.6-8.2) years after the index procedure. CONCLUSION/CONCLUSIONS:Within this large surveillance cohort of patients with colonic IBD and no additional high-risk features, having two consecutive negative colonoscopies predicted a very low risk of aCRN occurrence on follow-up. Our findings suggest that longer surveillance intervals in this selected population may be safe.

BACKGROUND & AIMS/OBJECTIVE:Patients with inflammatory bowel diseases (IBD) who have post-inflammatory polyps (PIPs) have an increased risk of colorectal neoplasia (CRN). European guidelines propose that patients with PIPs receive more frequent surveillance colonoscopies, despite limited evidence of this increased risk. We aimed to define the risk of CRN and colectomy in patients with IBD and PIPs. METHODS:We conducted a multicenter retrospective cohort study of patients with IBD who underwent colonoscopic surveillance for CRN, from January 1997 through January 2017, at 5 academic hospitals and 2 large non-academic hospitals in New York or the Netherlands. Eligible patients had confirmed colonic disease with duration of 8 years or more (or any duration, if they also have primary sclerosing cholangitis) and no prior history of advanced CRN (high-grade dysplasia or colorectal cancer) or colectomy. The primary outcome was occurrence of advanced CRN according to PIP status; secondary outcomes were occurrence of CRN (inclusive of low-grade dysplasia) and colectomy. RESULTS:Among 1582 eligible patients, 462 patients (29.2%) had PIPs. PIPs were associated with more severe inflammation (adjusted odds ratio [aOR], 1.32; 95% CI, 1.13-1.55), greater disease extent (aOR 1.92; 95% CI, 1.34-2.74), and lower likelihood of primary sclerosing cholangitis (aOR 0.38; 95% CI, 0.26-0.55). During a median follow-up period of 4.8 years, the time until development of advanced CRN did not differ significantly between patients with vs without PIPs. PIPs did not independently increase risk of advanced CRN (adjusted hazard ratio, 1.17; 95% CI, 0.59-2.31). The colectomy rate was significantly higher in patients with PIPs (P=0.01). CONCLUSIONS:In a retrospective analysis of data from 2 large independent surveillance cohorts, PIPs were associated with greater severity and extent of colon inflammation and higher rates of colectomy, but were not associated with development of any degree of CRN. Therefore, intervals for surveillance should not be shortened solely based on the presence of PIPs.

Purpose: Gastrointestinal bleeding (GIB) is a common complication of LVAD therapy. Previously, we retrospectively reviewed endoscopic evaluation and outcomes of GIB in LVAD recipients in our center and proposed an endoscopic management algorithm (Figure) to eliminate low yield procedures. Herein, we aimed to prospectively validate this algorithm. Method(s): We prospectively tested the algorithm in LVAD recipients who presented with GIB between June 2017 and August 2018. We compared the diagnostic and therapeutic yield of endoscopy and healthcare costs between conventional GIB management to the algorithm. Result(s): 33 LVAD pts with GIB were identified. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) pts. In total, 41 endoscopies localized a source in 23 (56%) resulting in 14 (36%) interventions at a median length-of-stay (LOS) of 8 d. Of 18 lesions identified, angiodysplasias were the most common (9, 50%) and the small bowel was the most common location (11, 48%). Despite non-adherence to the algorithm in 7 of 33 pts (21%), algorithm implementation increased the diagnostic yield by 70% (p=0.008) and therapeutic yield by 125% (p=0.01), reduced the number of procedures per pt by24% (p<0.01), LOS by 33% (p<0.01), and estimated costs by 18% (p<0.01) in comparison to our retrospective cohort (Table). Conclusion(s): Our endoscopic management algorithm of GIB in LVAD pts is effective in reducing low yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing healthcare resource utilization.