Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Both the chronic inflammation in inflammatory bowel disease (IBD), and its treatment, can increase the risk of malignancy. There is also an increasing number of patients with current and prior cancer who require IBD treatment. Thus, there is a complex interplay between immunosuppressive treatment and monitoring for new and recurrent cancer. RECENT FINDINGS/RESULTS:Vedolizumab and ustekinumab have not been shown to increase the risk of malignancy. Transplant data shows a potential risk with tofacitinib although rheumatoid arthritis data does not. IBD patients have been shown to tolerate chemotherapy, specifically with cytotoxic compared with hormonal chemotherapy. Patients with prior cancer are at increased risk of new or recurrent cancers; however, immunosuppression appears to be safe. Emerging treatments for IBD have demonstrated acceptable safety profiles for malignancy risk, and immunosuppression appears to be safe for use in patients with current and prior malignancy. More data is still needed to assess long-term risk of malignancy in these patients, especially with newer treatments.

BACKGROUND:GIB is a common complication of LVAD therapy accounting for frequent hospitalizations and high resource utilization. METHODS:We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, healthcare costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis. RESULTS: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. 41 endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation in comparison to our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (p<0.01), a 113% increase in therapeutic yield (p=0.01), a 27 % reduction in the number of procedures per patient (p<0.01), a 33% decrease in length of stay (p<0.01), and an 18% reduction in estimated costs (p<0.01). The same median number of red blood cell transfusions were used in the two cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) as compared to our conventional cohort (43.7%). CONCLUSIONS:Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, decreasing healthcare resource utilization and costs, while not increasing the risk of a re-bleeding event.

BACKGROUND:Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis. Alvimopan, an oral peripherally acting mu-opioid receptor antagonist approved for accelerating gastrointestinal recovery, has never been studied specifically in patients with inflammatory bowel disease (IBD). AIM/OBJECTIVE:To investigate the efficacy of alvimopan in preventing POI among IBD patients. METHODS:A retrospective chart review was conducted on 246 IBD patients undergoing bowel surgery between 2012 and 2017. Data collected included demographics, IBD subtype, length of stay (LOS), postoperative gastrointestinal symptoms, and administration of alvimopan. The primary outcome was POI; secondary gastrointestinal recovery outcomes were: time to first flatus, time to first bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and LOS. RESULTS:When compared with the control group, patients in the alvimopan group had shorter times to tolerating liquids and solids, first flatus, and first bowel movements (p < 0.01). LOS was shorter in the alvimopan group when compared with controls (p < 0.01). The overall incidence of POI was higher in controls than in the alvimopan group (p = 0.07). For laparoscopic surgeries, the incidence of POI was also higher in controls than in the alvimopan group (p < 0.01). On multivariable analysis, alvimopan significantly decreased time to all gastrointestinal recovery endpoints when compared to controls (p < 0.01). CONCLUSIONS:Alvimopan is effective in accelerating time to gastrointestinal recovery and reducing POI in IBD patients. While the benefits of alvimopan have been demonstrated previously, this is the first study of the efficacy of alvimopan in IBD patients.

BACKGROUND AND AIMS/OBJECTIVE:Little is known about the clinical significance of indefinite dysplasia (IND) in patients with inflammatory bowel diseases (IBD) undergoing colonoscopic surveillance for colorectal neoplasia. METHODS:We conducted a retrospective cohort analysis of 492 patients with colonic IBD for 8 or more years or concomitant primary sclerosing cholangitis, with no history of advanced colorectal neoplasia (high-grade dysplasia or colorectal cancer) or colectomy, undergoing colorectal neoplasia surveillance at tertiary IBD referral center from 2001 through 2017. Subjects received consistent histopathologic grading of dysplasia. We collected data on time to development of (advanced) colorectal neoplasia or colectomy using Kaplan Meier methods. We identified factors independently associated with (advanced) colorectal neoplasia with multivariable Cox regression analysis. RESULTS:After 2149 person-years of follow-up, 53 patients (10.8%) received a diagnosis of IND without prior or synchronous low-grade dysplasia (LGD). Compared to patients without dysplasia, patients with IND had a significantly higher risk of advanced colorectal neoplasia (adjusted hazard ratio, 6.85; 95% CI, 1.78-26.4) and colorectal neoplasia (adjusted hazard ratio, 3.25; 95% CI, 1.50-7.05), but not colectomy (P=.78). Compared to IND, LGD was associated with a significantly higher risk of advanced colorectal neoplasia (P=.05). Following a diagnosis of no dysplasia, IND only, or LGD, the incidence rates of advanced colorectal neoplasia were 0.4% per patient-year, 3.1% per patient-year, and 8.4% per patient-year, respectively. CONCLUSIONS:In a retrospective analysis of patients with IBD undergoing colorectal neoplasia surveillance with consistent histopathologic grading of dysplasia, IND was independently associated with a significant increase in risk of advanced colorectal neoplasia. These findings require validation and if confirmed, a reappraisal of the colorectal neoplasia surveillance guidelines.

BACKGROUND & AIMS/OBJECTIVE:Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBD). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD. METHODS:We conducted a retrospective cohort study, collecting data from 5 medical centers on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission. RESULTS:Our analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD-unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse following a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18-2.71; HR for immunomodulators, 2.22; 95% CI, 1.38-3.55; HR for biologics, 1.95; 95% CI, 1.01-5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21-3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01-3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank=0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission. CONCLUSIONS:In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

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

INTRODUCTION: Diarrhea is a common complication of HIV/AIDS. Although non-infectious enteropathy may be attributed to HIV infection, enteric pathogens are frequently detected in episodes of diarrhea. The objective of this study was to investigate the relationship between CD4 count and enteric infection as detected by multiplex gastrointestinal PCR stool testing in HIV/AIDS patients.
METHOD(S): We performed a cross-sectional analysis of adult inpatients and outpatients who underwent stool testing with a FilmArray multiplex gastrointestinal pathogen PCR panel (GI PCR panel) during an acute episode of diarrhea from December 2015 to February 2019. Our primary endpoint was the detection of any enteric pathogen. Patients were stratified by the presence of HIV infection and CD4 count at time of stool testing.
RESULT(S): Of 80 HIV+patients who underwent a GI PCR panel, 45 (56%) tested positive for an enteric pathogen (Table 1). HIV+patients with CD4 counts >500 (n=26) were more likely to have a pathogen detected (19, 73%) compared to patients with a CD4 count <200 (n=30) consistent with AIDS (12, 40%; P=0.03; Figure). Patients with a CD4 count between 201 and 499 (n=24) had a positivity rate that was in between that of patients with low and high CD4 counts (14, 58%). Of 30 AIDS patients, 9 (30%) had a GI infection not detected by GI PCR including CMV, HSV, LGV, MAI, and syphilis. Among this subset of 9 AIDS patients, 4 (44%) tested negative on GI PCR. AIDS patients were less likely to be adherent to antiretroviral therapy, and more likely to be on opportunistic infection prophylaxis compared to HIV+patients with CD4 counts >200 (P=0.03 and P=0.002 respectively.) Compared to patients with CD4 counts >200, those with AIDS were more likely to receive empiric antimicrobial therapy at stool testing (P<0.001), and in the 30 days following stool testing, as likely to visit an emergency room (P=0.24), require hospitalization (P=0.31), or undergo endoscopic procedures for continued GI symptoms (P=0.67).
CONCLUSION(S): Enteric infections were common in HIV+patients who underwent a GI PCR panel for an episode of diarrhea, with the highest proportion of positive results in patients with CD4 counts >500. Based on historical data, this rate of positivity is considerably higher than in the general population of patients with an episode of diarrhea. These data suggest that AIDS patients may be more likely to have a pathogen not included on the GI PCR panel, or a chronic cause of diarrhea such as HIV-enteropathy

INTRODUCTION: Diarrhea is a common sequela of solid organ transplantation. Post-transplant diarrhea may be attributed to non-infectious causes including medications, however the contribution of infectious etiology is unclear. The objective of our study was to evaluate the relationship between post-transplant immunosuppression and enteric infection as detected by multiplex gastrointestinal PCR stool testing in solid organ transplant (SOT) recipients.
METHOD(S): We performed a multicenter cross-sectional analysis of inpatient and outpatient SOT recipients who underwent stool testing with a FilmArray multiplex gastrointestinal pathogen PCR panel (GI PCR panel) during an acute episode of diarrhea from April 2016 to May 2019. The primary endpoint was the detection of any enteric pathogen. Patients were stratified by the number of major classes of immunosuppressive agents, including calcineurin inhibitors, anti-proliferative agents, and corticosteroids, at time of stool testing.
RESULT(S): We identified 232 SOT patients who underwent a GI PCR panel comprising 52 (23%) lung, 84 (36%) kidney, 41 (18%) heart, and 55 (24%) liver transplants. 92 (40%) tested positive for an enteric pathogen. Patients whose immunosuppressive regimen included 3 medications (n = 139) were more likely to have a gastrointestinal pathogen detected (63, 45%) compared to patients on 2 immunosuppressive medications (P = 0.02; Figure 1) Renal transplant patients were more likely to have an enteric pathogen detected (60%; P < 0.0001) compared to other organ types, and more likely to be on 3 immunosuppressive medications (P < 0.01). Viruses, specifically norovirus and sapovirus, and bacteria, including C. difficile and E. coli subtypes, were common in transplant recipients on 2 immunosuppressive agents (Table 1). Of 139 patients on 3 immunosuppressive agents, 89 (59%) were more likely to be on opportunistic infection prophylaxis for CMV and P. jiroveciipneumonia compared to those patients on 2 drugs (P < 0.001). In the 30 days following stool testing, all SOT recipients, regardless of the number of immunosuppressive drugs, were as likely to visit an emergency room (P = 0.57), require hospitalization (P = 0.66), or undergo endoscopic procedures for persistent GI symptoms (P = 0.78).
CONCLUSION(S): Gastrointestinal infections, particularly enteric viruses, were common in SOT recipients who underwent a GI PCR panel for an episode of post-transplant diarrhea, with the highest proportion of positive results in patients maintained on 3 or more immunosuppressive agents