Christina Y. Ha

Risk of arterial thrombotic events in inflammatory bowel disease.

OBJECTIVES:Patients with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events. The risk of arterial thrombotic events in IBD, however, has been less well characterized. We explored whether Crohns disease (CD) and ulcerative colitis (UC) are associated with a higher risk for thrombotic events involving the mesenteric, cardiac, or cerebral arteries.METHODS:Using the Thomson Reuters MarketScan Research claims database, we conducted a retrospective cohort study of IBD patients observed for the occurrence of pre-defined thrombotic events. For comparison, four non-IBD controls were age-, sex-, and index date–matched to each IBD case. The outcomes of interest were acute mesenteric ischemia, transient ischemic attack, cerebrovascular occlusion, atherosclerosis, peripheral vascular disease, and myocardial infarction. We performed a multivariate analysis adjusting for potential confounders for thrombotic events, including hypertension, diabetes, hyperlipidemia, and, in women, the use of contraceptives. We calculated the adjusted hazard ratios (HRs) for each event by comparing IBD patients with controls and used the log-rank test to determine statistical significance.RESULTS:The study included 17,487 IBD patients and 69,948 controls. Overall, IBD patients had a markedly increased risk of acute mesenteric ischemia (HR=11.2, P<0.001). IBD patients as a whole did not have an increased risk of other arterial thrombotic events, including myocardial infarction and transient ischemic attack, when compared with controls. However, women with IBD who were over the age of 40 years had a higher risk of myocardial infarction (HR=1.6, P=0.003). In addition, women with IBD below the age of 40 years who showed a significantly higher risk for stroke (HR=2.1, P=0.04). For all events, the risks in CD and UC were similar.CONCLUSIONS:Patients with IBD have a markedly increased risk of acute mesenteric ischemia. Subgroup analysis reveals that women over the age of 40 years with IBD are at increased risk of myocardial infarction, whereas those below the age of 40 years exhibit a two-fold higher risk for stroke. In contrast, men with IBD did not share these same risks for arterial thrombotic events.

Patients With Late-Adult-Onset Ulcerative Colitis Have Better Outcomes Than Those With Early Onset Disease

BACKGROUND & AIMS The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. METHODS We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. RESULTS Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). CONCLUSIONS Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis.

Probiotics as therapy in gastroenterology: a study of physician opinions and recommendations.

Goals The objective of this study was to determine how gastroenterologists perceive and use probiotic-based therapies in practice. Background In the United States, there has been a recent increase in research investigating the therapeutic capacities of probiotics in human disease and an accompanying increase in product availability and marketing. How medical care providers have interpreted the available literature and incorporated it into their practice has not been earlier assessed. Study A 16-question survey (see Survey, Supplemental Digital Content 1, http://links.lww.com/JCG/A14) was distributed to practicing gastroenterologists and physicians with a specific interest in GI disorders within a large metropolitan area. Results All physicians responded that they believed probiotics to be safe for most patients and 98% responded that probiotics have a role in treating gastrointestinal illnesses or symptoms. Currently 93% of physicians have patients taking probiotics most often for irritable bowel syndrome. Commonly used probiotics included yogurt-based products, Bifidobacterium infantis 35624 (Align), and VSL#3. Most surveyed physicians recommended probiotics for irritable bowel syndrome, antibiotic, and Clostridium difficile-associated diarrhea because they believed that the literature supports their usage for these conditions. However, physician practice patterns did not consistently correlate with published, expert-panel-generated recommendations for evidence-based probiotic use. Conclusions This study suggests most gastrointestinal disease specialists recognize a role for and have used probiotics as part of their therapeutic armamentarium; however, the effective implementation of this practice will benefit from additional supporting studies and the eventual development of clinical practice guidelines supported by the major gastroenterology societies.

Diagnosis and management of GI stromal tumors by EUS-FNA: a survey of opinions and practices of endosonographers

BACKGROUND There is no consensus regarding the best management strategy for diagnosing and treating GI stromal tumors (GISTs). OBJECTIVE Our purpose was to examine the practice patterns of endosonographers in diagnosing and managing GISTs, particularly features of GISTs suggestive of malignancy, features that prompt surgical referral, and surveillance patterns. DESIGN An invitation to complete an online survey was e-mailed to all 413 members of the American Society for Gastrointestinal Endoscopy EUS Special Interest Group. RESULTS A total of 134 (32%) members responded; 59% of respondents use EUS features combined with FNA findings to diagnose GIST, and 89% consider a c-kit-positive stain on FNA most suggestive of GIST. However, 60% would diagnose GIST when cytologic samples are insufficient for diagnosis, and 40% would diagnose GIST if cytologic samples are sufficient but c-kit is negative. A total of 92% use size as the main criterion to distinguish benign from malignant GISTs, and 90% refer lesions >5 cm for surgery. For lesions not resected, 70% survey annually, 19% less than annually, 10% more than annually, and 1% do not survey. LIMITATIONS The opinions of the respondents do not necessarily reflect the opinions and practices of endosonographers nationwide. There are inherent limitations to an online multiple-choice survey, including low response rates. CONCLUSIONS There are substantial practice variations in diagnosing, resecting, and surveying GISTs. A majority of our survey respondents have made the diagnosis of GIST without FNA confirmation. Size >5 cm is the feature used most to predict malignancy and to prompt surgical referral. Surveillance practices for unresected GISTs are variable. Evidence is needed to establish practice guidelines in this area.

104 Increased Incidence of Post-Operative Complications in Older Inflammatory Bowel Disease Patients Having Intestinal Surgery

Data on long-term outcome of paediatric-onset Crohns disease (CD) are scarce. Methods: All patients under the age of 17 years at diagnosis of definite or probable CD between 1988 and 2004 recorded by EPIMAD Registry were included. Results: 538 patients with paediatriconset CD were identified (8.5% of all cases of CD), including 293 males. The median age at diagnosis was 14 years [IQR: 12-16] and the median duration of follow-up was 11.5 years [IQR: 7-15]. Disease location was stable over time in 75% of them, 11% of patients progressed to more extensive disease, and healing of colonic lesions during follow-up was reported in 14% of patients with ileocolonic disease (L3 according to Montreal classification). The percentage of complicated behaviour (B2 or B3 according to Montreal classification) increased from diagnosis to last news: 73% vs 42% (B1); 24% vs 39% (B2); and 4 % vs 19 % (B3); p<10-3. Cumulative probabilities of receiving immunosuppressors and anti-TNF therapy were respectively 22% et 2% at 1 year, 51% and 16% at 5 years, 66% and 29% at 10 years, and 74% and 49% at 20 years. Cumulative probabilities of first intestinal resection were 9%, 15%, 31%, 44% and 54% at 1, 2, 5, 10 and 20 years. Conclusion: In this large population-based cohort, the natural history of paediatric-onset CD was characterized by a stable disease location in 75% of patients and a complicated behaviour in 60% of them after a median follow-up of 11.5 years. Twenty years after diagnosis, three-quarters of patients would have received immunosuppressors, about half an anti-TNF therapy, and half of patients would have required an intestinal resection. (1) Chouraki et al. Aliment Pharmacol Ther 2011

Clinical presentation and outcomes of inflammatory bowel disease patients admitted to the intensive care unit.

Background: Disease severity, immunosuppression, and malnutrition may impact morbidity and mortality of the critically ill patient with inflammatory bowel disease (IBD). The aim of this study was to identify potential predictive factors for mortality among IBD patients requiring admission to an intensive care unit (ICU). Methods: All patients with an admitting diagnosis of ulcerative colitis or Crohn’s disease presenting to the ICU at the Mount Sinai Medical Center from 2003 to 2008 were retrospectively analyzed. Data regarding IBD-specific features, medications, and surgical outcomes were collected as well as ICU-related morbidity and 30-day mortality. Results: Ninety-five patients were admitted to the ICU out of a total of 6663 IBD-related hospital admissions with an overall 30-day mortality rate of 18.9%. The annual number of ICU admissions of all hospitalized IBD patients increased from 0.1% in 2003 to 2.6% of admissions in 2008. ICU-related variables associated with increased mortality included mechanical ventilation (P=0.0002), vasopressor requirement (P=0.0002), severe sepsis (P=0.0005), acute kidney injury (P=0.001), Acute Physiology and Chronic Health Evaluation II scores (P⩽0.0001), hypoalbuminemia (P=0.036), and thromboembolism (P=0.046). On multivariate analysis, elevated Acute Physiology and Chronic Health Evaluation II scores were the only independent predictor of mortality. Conclusions: Although the overall number of ICU admissions among IBD patients was low, the annual incidence rates of admissions are increasing. This patient subgroup had significant in-hospital morbidity and 30-day mortality. Earlier identification of potential risk factors leading to poorer outcome, particularly within the first 24 hours of ICU admission, may impact the triage and subsequent management of these critically ill patients.

Su1352 Prevalence and Characteristics of Previously Undetected (Surprise) Colorectal Cancer in Colectomy Specimens Among Patients With Inflammatory Bowel Disease

Background/Aims: An altered intestinal microbial composition (dysbiosis) is associated with intestinal inflammation in inflammatory bowel disease, which are characterized by decreased bacterial diversity and an altered ratio of beneficial and aggressive bacterial species. We analyzed intestinal microbial profiles of feces and mucosal tissues from Korean inflammatory bowel diseases (IBD) patients and healthy controls (HC) using high-throughput sequencing method. Methods: Fecal or mucosal tissue DNA were isolated from 35 Crohns disease (CD) patients, 20 ulcerative colitis (UC) patients and 31 HC. Variable regions V1-V3 of the 16S rRNA gene were amplified from all samples. PCR products were sequenced using 454 GS FLX Titanium sequencing. The composition, diversity and richness of microbial communities were determined and compared among CD, UC and HC. Results: Intestinal microbial profile of fecal samples in Korean HC was similar toWestern HC data with predominant proportions of phyla Firmicutes and Bacteroidetes. Global structure and individual bacterial abundance were different between feces and ileal tissues in HC. Ileal tissues of active CD patients had higher level of phylum Proteobacteria, lower level of phylum Firmicutes, and decreased bacterial diversity compared to UC and HC. The proportion of phylum Fusobacteria was significantly higher in active CD patients compared to HC and CD patients in remission. No significant differences of mucosal bacterial composition between UC patients and HC. Conclusions: Our 16S rRNA sequence data demonstrates a community-level dysbiosis in Korean IBD patients. Fecal microbiota analysis does not effectively reflect ileal bacterial community structure. Intestinal microbial composition of UC tend to be closer to that of HC, suggesting different roles of intestinal microbiota in the pathogenesis of CD and UC. Acknowledgement: This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (A120176)

Rescue Diverting Loop Ileostomy: An Alternative to Emergent Colectomy in the Setting of Severe Acute Refractory IBD-Colitis

BACKGROUND: Severe acute refractory colitis has traditionally been an indication for emergent colectomy in IBD, yet under these circumstances patients are at elevated risk for complications because of their heightened inflammatory state, nutritional deficiencies, and immunocompromised state. OBJECTIVE: We hypothesized that rescue diverting loop ileostomy may be a viable alternative to emergent colectomy, providing the opportunity for colonic healing and patient optimization before more definitive surgery. DESIGN: This was a retrospective case series. SETTINGS: The study was conducted at a single academic center. PATIENTS: Patients with severe acute medically refractory IBD-related colitis were included. INTERVENTION: Rescue diverting loop ileostomy was the intervening procedure. MAIN OUTCOME MEASURES: The primary outcome was avoidance of urgent/emergent colectomy. The secondary outcome was efficacy, defined by 3 clinical aims: 1) reduced steroid dependence or opportunity for bridge to medical rescue, 2) improved nutritional status, and 3) ability to undergo an elective laparoscopic definitive procedure or ileostomy reversal with colon salvage. RESULTS: Among 33 patients, 14 had Crohn’s disease and 19 had ulcerative colitis. Three patients required urgent/emergent colectomy, 2 with ulcerative colitis and 1 with Crohn’s disease. Across both disease cohorts, >80% of patients achieved each clinical aim for efficacy: 88% reduced their steroid dependence or were able to bridge to medical rescue, 87% improved their nutritional status, and 82% underwent an elective laparoscopic definitive procedure or ileostomy reversal. A total of 4 patients (11.7%) experienced a postoperative complication following diversion, including 3 surgical site infections and 1 episode of acute kidney injury. LIMITATIONS: The study was limited by being a single-center, retrospective series. CONCLUSIONS: Rescue diverting loop ileostomy in the setting of severe, refractory IBD–colitis is a safe and effective alternative to emergent colectomy. This procedure has acceptably low complication rates and affords patients time for medical and nutritional optimization before definitive surgical intervention. See Video Abstract at http://links.lww.com/DCR/A520.

552 Serrated Epithelial Change is Associated With a Longer Time to Dysplasia in Patients With Chronic Ulcerative Colitis

Background: The chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, is associated with a reduction in risk for colorectal and other cancers. However, when used chronically, these drugs carry a significant side effect to induce GI bleeding. Our laboratory has developed a class of NSAIDs that are complexed with phosphatidylcholine (PC-NSAIDs) which have been shown in preclinical and clinical trials to reduce NSAID GI toxicity. To date these drugs have been shown to possess equal or better efficacy compared to traditional NSAIDs in regard to anti-inflammatory, analgesic and anti-pyretic activities. To evaluate the chemopreventive activity of PC-NSAIDs, an animal model of carcinogeninduced colonic aberrant crypts was tested. Methods: Rats were treated at two weekly intervals with azoxymethane (AOM, 15mg/kg), followed two weeks later by daily oral dosing with control or test drugs for 4weeks (indomethacin, 2mg/kg; indomethacin-PC, 2mgNSAID/ kg; ibuprofen, 20mg/kg; ibuprofen-PC, 20mg NSAID/kg; or aspirin-PC, 20mg NSAID/kg). Assessments were made of GI toxicity/bleeding by measurement of the hematocrit and of hemoglobin in the feces, and of chemopreventive efficacy by the number of aberrant crypts in the distal colon. Results: At the doses used, no GI toxicity was detected from any of the test agents. The number of colonic aberrant crypts were significantly reduced by treatment with indomethacin-PC, but not by indomethacin (AOM control=40±11; indomethacin= 46±9; indomethacin-PC=10±2). In a separate study colonic aberrant crypts were significantly reduced by treatment with ibuprofen-PC and aspirin-PC, but not by ibuprofen (AOM control=133±18; ibuprofen=189±32; ibuprofen-PC=76±8; aspirin-PC=86±24). Conclusions: At equivalent doses, a novel class of PC-NSAIDs exhibit enhanced chemopreventive activity over traditional NSAIDs in a rodent model of colon carcinogenesis. (Supported by NIH grants R41CA171408 and R03CA171613).

Sa1096 Patient or Procedural Factors: What Drives Readmission After Surgery for Crohn's Disease?

Background: Hospital readmission is associated with increased cost and worse patient outcomes. Readmission has emerged as a surrogate metric of quality. Crohns disease (CD) patients requiring surgical management are at risk for hospital readmission, which may delay additional therapies. The aim of this study was to assess readmission rates at a tertiary IBD referral center and risk factors in post-operative CD patients in order to identify areas to target for improvement. Methods: We performed a cohort study of colorectal surgery patients captured in the National Surgical Outcome Improvement Program (NSQIP) database with the discharge ICD-9 diagnostic code of 555.x (Crohns disease, CD) between January 2009-January 2012. Variables of interest included pre-operative medications, disease behavior and phenotype, and pre-operative comorbidities. Primary outcomes of interest were 30day post-operative readmission and post-operative complications. Results: There were 114 Crohns patients admitted for surgical management of CD over the 3-year period with a 30-day readmission rate of 19.2% (n=22). Within this cohort, the 30-day post-operative complication rate (medical and/or surgical) was 19.2% (95% CI 10.9-24.7). Disease behavior (p=0.09) and location (p=0.70) were not significantly associated with readmission rates. Post-operative complications were the primary risk factor for readmission with 45.5% of readmitted patients experiencing post-operative complications compared to 13.0% among patients not requiring readmission (p=0.002). Average length of stay for the index admission was longer in readmitted patients compared to those not readmitted (13.9 ± 2.8 vs 8.0 ± 0.5 days; p=0.0008). Pre-operative steroid, biologic and immunomodulator use, TPN, weight loss, anemia, prior surgical history, disease duration or emergent surgery were not associated with readmission. Conclusions: Readmission after Crohns disease surgery is primarily driven by the presence of post-operative complications, not CD location or phenotype. Efforts to reduce 30-day readmissions should focus on early recognition and prevention of postoperative complications. Further study is needed to determine the impact of readmission on the timeline for resuming CD therapies to prevent early disease recurrence.