History Of Intestinal Resection Research Articles

The fulminant form of pseudomembranous colitis in a child with cystic fibrosis

Аnnotation. A long-term persistent infection of the lower respiratory tract with cystic fibrosis and, as a consequence, the need for regular use of antibacterial drugs inevitably leads to changes in the composition of the intestinal microflora. At the same time, the most dangerous are toxigenic strains of Clostridium difficile. In turn, excessive growth of C. Difficile leads to increased sensitivity of enterocytes to its toxins. The leading pathogenicity factors of C. Difficile are exotoxins A (TcdA), B (TcdB) and binary toxin. TcdA and TcdB are enterotoxins acting on intestinal enterocytes, which leads to inflammation and necrosis of the mucous membrane. The binary toxin forms a complex on the enterocyte membrane that penetrates the cytoplasm, disrupts the functioning of the cell, leads to its death, and also enhances the adhesion and colonization of C. Difficile. One of the most accessible methods for determining the presence of toxin-producing C. Difficile in feces is immunochromatographic examination. The frequency of such a complication in patients with MV is unknown, the literature presents isolated cases of such a complication in Russia. There is one known case of fulminant pseudomembranous colitis (lethal). A clinical case of fulminant pseudomembranous colitis with recovery is presented. Conclusion. Patients with cystic fibrosis are at risk for the development of this complication, especially patients with a history of intestinal resection against the background of meconium ileus. In about 5% of cases, there is a fulminant course of pseudomembarnous colitis. In this form, the duration of the disease can be several hours. Lethality in the lightning-fast course reaches 58-70%. This option presents the greatest difficulty in terms of diagnosis due to atypical clinical symptoms. In particular, the diarrheal syndrome may not be pronounced or absent at all. Such patients often show symptoms of an acute abdomen, which makes differential diagnosis difficult. This is confirmed in our clinical case. It is necessary to increase awareness and alertness of doctors regarding the risk of developing this formidable complication in patients with Сystic fibrosis

Famitinib for familial adenomatous polyposis-associated aggressive desmoid tumors: A single-center exploratory study.

10513 Background: Desmoid tumour (DT) is a common extra-intestinal manifestation of familial adenomatosis polyposis (FAP), with high risk of recurrence and became the second leading cause of FAP patients’ death. The treatment of FAP-associated DTs are limited. Famitinib is a orally bioavailable, tyrosine kinase inhibitor against VEGFR-2, PDGFR, c-kit, and FGFR, and has shown antitumor activity in these patients (pts). Methods: This is a prospective, single arm study of FAP pts with progressing DT per RECIST v1.1, treated with famitinib 20 mg QD since 11/2021. The primary endpoint was objective response rate (ORR), with secondary endpoints of safety, progression-free survival (PFS), and quality of life (EORTC QLQ C30). We also collected the FFPE slices of DTs to test both genetic and proteomic backgrounds of pts with different therapeutic results. Results: Between Nov 24, 2021 and Aug 8, 2022, 11 pts were enrolled and evaluated every 9 weeks. The median follow-up time was 9.4 m (6.6 to 14.9 m). The median age was 36 (28-53) and 45% were male. Nine pts were diagnosed with intra-abdominal (IA) tumors while two had extra-abdominal (EA) DTs. Eight had stage III-IV DTs with rapid growth and severe symptoms. 10 of them had history of intestinal resection. Two pts were treated with dacarbazine and epirubicin before enrollment, while one patient received radiotherapy before famitinib. Five pts achieved partial response (PR) and six achieved stable disease (SD), with a median time to response of 7.0 months. The ORR was 45.5% and the disease control rate (DCR) was 100%. The 6-month PFS rate was 91%. The ORR of pts with IA DTs was 55.6%. Of adverse events (AEs) with famitinib, 87% were grade 1/2, the most frequently reported being hypertension (73%), neutropenia (64%), bilirubinemia (55%) and proteinuria (36%). Mean global health status/QoL before and after 6 months’ treatment was 58.3 vs 75.8 ( P= 0.09). Of all 11 pts, germline APC mutations scattered from codon 457 to 1578, and five of them detected somatic APC mutations from codon 547 to 1896 in DTs. Correlative study analysis will be presented. Conclusions: Famitinib demonstrated promising efficacy and a favorable safety profile in FAP-associated aggressive DTs.

P513 Treatment persistence in bio-naive patients with long-standing Crohn’s disease treated with first-line biologics: real-life data from a Croatian tertiary center

Abstract Background All available biologics have demonstrated efficacy and safety as first-line treatment options for bio-naive Crohn’s disease (CD) patients. Real-world data about persistence with biologic treatment in patients with CD are lacking. The aim of this study was to assess and to identify potential factors affecting treatment persistence with index biologic medication in our tertiary center. Methods A single-center, noninterventional, retrospective chart review study (January 2015-October 2020) was performed on real-life data of adult bio-naïve CD patients who were treated with infliximab, adalimumab, vedolizumab or ustekinumab for >12 months duration of drug exposure. Treatment persistence was assessed using Kaplan-Meier analysis for a 36 month period and t-test for independent samples was used to identify predictors of long-term biologic persistence rates. Results Out of 84 patients (51.7% female; median age 33) included in the study 38.4% were smokers, 34.5% had history of intestinal resection and 25.6% had extraintestinal manifestations of CD. At the start of the biologic-induction regime 35.7% of patients were treated with corticosteroids and 43.4% with concomitant immunomodulator (81.8 % azathioprine, 18.2 % methotrexate). The median of CD duration was 47 months and the mean duration of treatment persistence was 29 months. After 36 months of treatment duration, the persistence rates for ustekinumab, adalimumab and infliximab were 61.9%, 56% and 48.1% respectively. Vedolizumab results were omitted from final analysis due to the small number of patients treated with the drug (N=3). Factor associated with higher persistence was body mass index (BMI) > 25 kg/m2 at the time of biologic therapy induction (p=0.05). Concomitant therapy with immunomodulator numerically significantly prolongs the therapy persistence (33.6 vs. 24.5 months). No other patient or disease-related factors (including disease duration) were found to be associated with treatment persistence for studied biologics. Conclusion These real-world data suggest that infliximab, adalimumab and ustekinumab are effective and efficient therapeutic options for bio-naive patients with moderate to severe long-standing Crohn′s disease. Concomitant immunomodulatory therapy and BMI >25 kg/m2 at the time of therapy induction were factors associated with higher biologic treatment persistence in those patients.

P473 Real world experience with the Crohn’s Disease Exclusion Diet (CDED) in a tertiary IBD clinic

Abstract Background The Crohn’s Disease Exclusion Diet (CDED) is a whole-food diet designed to reduce exposure to dietary components, hypothesized to negatively affect the microbiome, intestinal barrier, and immune response. In a clinical study in adults with mild-moderate CD (<5 years duration), an inflammatory phenotype involving the terminal ileum, it induced clinical, biochemical and endoscopic disease remission. We aimed to describe our real-world experience with the CDED, in a clinically diverse CD population. Methods A retrospective cohort study of CD patients prescribed with the CDED, between 1.2018 and 11.21. Patients’ medical background, medical therapy, nutritional status and clinical disease activity as well as adherence and clinical outcomes were documented from patients’ medical files. Results The CDED was recommended to 218 CD patients. Of these, 62 were excluded from the analysis due to lack of medical information (n=11), prior personal experience with the CDED (n=23), patient’s refusal (n=24), and stoma patients (n=4). The CDED was initiated in 155 patients (age 37.7±16.3, 66% men, disease duration 7.8±9.6), 35.3% had colonic/ileo-colonic disease, 23.7% and 25% had a stricturing and penetrating disease respectively, 27.5% had a history of intestinal resection, 19.9% had extra-intestinal involvement, and 7.7% had a severe endoscopic disease at diet initiation. Indications for therapy included patient’s will (44.7%), adjunctive therapy (23.7%), bridge with biologic induction (20.4%), rescue therapy (3.9%), exhaustion/contraindication of other advanced therapy options (1.4%), de-escalation of biologics (0.7%), preparation for surgery (0.7%), and others (3.9%). Upon initiation, 67.3% (n=105) had an active disease [Harvey Bradshaw index (HBI) ≥5 / Calprotectin ≥250 g/l] and 32.7% were in remission. Physician and dietician follow-up at the end of phase 1 was documented in 89 (57.4%) and 74 (47.7%) of patients with an active disease (mean follow-up period 14.6±9.3 weeks). Fifty-eight percent of patients with dietary follow-up (n=43) were fairly-fully compliant to the CDED. Clinical response (drop in HBI>2 points) and remission (HBI<5) at the end of phase 1, were achieved by 58.9% (n=62) and 57.5% (n=60) of patients who were treated for an active disease (n=105). Clinical remission rate at the end of phase 1 was lower among patients with higher baseline HBI score (P for trend=0.028), lower dietary adherence (P for trend<0.001) and a surgical history (P=0.033). Conclusion The CDED may have efficacy across different clinical scenarios. Adherence is reasonable, and is associated with higher remission rates among patients treated for an active disease.

Physical development and its relationship to the metabolic activity of the intestinal microbiota in young children

Introduction. The metabolic activity of the intestinal microbiota is an important indicator of the functioning of the digestive tract, one of the main functions of which is the absorption of nutrients.The aim of the study was to analyze the content of short chain fatty acids in feces and assess their relationship with the indicators of physical development in children 3 years of age.Materials and methods. A prospective cohort study was conducted in 89 children 3rd year of life. The 1st observation group included children of the I and II health groups, the children of the 2nd group underwent surgical treatment on the intestine in the first months of life, the children of the3rd group are with atopic dermatitis. FD assessment was carried out in accordance with WHO recommendations (2017) the spectrum of FGC in feces was determined by gas-liquid chromatography.Results. It was determined the features of the rates of FD in healthy children, children with a history of intestinal resection and children with atopy in relation to the indicators of metabolic activity of the intestinal microbiota. The percentile distribution of the values of FGC in feces and their comparative assessment in the observation groups are given.Discussion. The content of FGM in feces has differences depending on the health status of children of the 3rd year of life. Different level of FGC shows a close relationship with the indicators of FD. Conclusions. A decrease in growth rates (body length SD: from -1 to -2) was revealed at low values (<25%) of the amount of acids, with an increase in propionate (25%) in feces. Reduced nutrition (body weight SD: from -1 to -2) it was associated with low values of the sum of isoacids and AI(-) (<25%); by 3rd year of life, the risk of low nutrition decreased in 4 times with high values (75%) of the sum of acids in feces (OR=4.33[1.09-17.71]). The multidirectionality of the content of fecal matter in young children and their influence on the indicators of FD emphasizes the versatility of the functions of the intestinal microbiota, which has a local and systemic effect on the human body.

P068 Racial and Socioeconomic Disparities in Acute Care Utilization in a National Cohort of Veterans With IBD.

Hospitalizations for Black patients with inflammatory bowel disease (IBD) have increased in recent decades though our understanding of disease behavior in Black patients remains limited and concerns related to healthcare equity persist. Existing data are largely drawn from small case series at IBD referral centers or national registries lacking granular longitudinal outpatient data. Our aim was to determine whether there are racial or socioeconomic disparities in acute care utilization as measured by hospitalizations and emergency department (ED) visits within a large national cohort of IBD patients. National Veterans Heath Administration (VHA) data were used to examine baseline disease characteristics and two years of utilization following an index outpatient gastroenterology visit for Crohn's disease (CD) or ulcerative colitis (UC) in 2017. To account for patients more likely to access care outside the VHA, we excluded those with less than four unique VHA encounters per year. We compared differences in comorbidity burden [Charlson comorbidity index, (CCI)], disease duration, surgical history and modifiable IBD severity risk factors (opioid use, tobacco use, biologic agent use, anemia, malnutrition) based on race and area deprivation index (ADI), a multidimensional marker for regional socioeconomic status (SES). Negative binomial regression was used to model demographic and clinical risk factors associated with hospitalization and ED visits. 19,442 patients (47.4% with CD and 52.6% with UC) were included: 14% Black, 5% Hispanic and 76% White. Compared to White patients, Black patients were younger, more likely to have anemia, perianal disease, and be in the bottom quartile of ADI; they were less likely to have a history of intestinal resection. IBD type, disease duration, CCI, and rates of tobacco use, opioid use, and malnutrition were not different between Black and White patients. On bivariate analysis, Black patients had increased mean and median ED visits compared to White patients (mean 4.48 vs 3.32; p < 0.001) though no differences were seen in hospitalizations (mean 0.96 vs 0.92; p=NS). On stepwise multivariable modeling, hospitalization and ED utilization were significantly higher among Black patients when controlling for age, sex, type of IBD, and disease duration [OR for hospitalization: 1.114 (95% CI: 1.046-1.199); OR for ED visit: 1.191 (95% CI: 1.125-1.261)]. After sequential adjustment for CCI and modifiable IBD severity risk factors, no differences in hospitalizations were seen between Black and White patients. In the full model for ED visits including adjustments for modifiable IBD severity risk factors (all significant), Black race was significantly associated with increased frequency of ED access [OR: 1.261 (95% CI: 1.19-1.336)], while ADI was not. In this analysis of a large national outpatient cohort of patients with IBD, we identified significant racial differences in IBD disease behavior, anemia and subsequent acute care utilization. Racial differences in hospitalization were not significant after controlling for modifiable IBD risk factors suggesting actionable targets to mitigate the observed disparities. However, Black race was independently associated with ED utilization even in a healthcare system where access to care is theoretically similar. Future studies should investigate factors underlying increased ED utilization among Black IBD patients in further detail.

P218 Assessment of the degree of intestinal destruction in Crohn’s disease at the time of diagnosis

Abstract Background Certainly the presence of advanced intestinal lesions in Crohn’s disease (CD) is associated with a more frequent recourse to surgical resection. However, in general, the degree of intestinal destruction in patients with CD is not assessed at the time of diagnosis, and the natural history of CD may differ phenotypically from patient to patient. The aim of this study was to assess the degree of intestinal destruction in patients with CD at the time of diagnosis, using the Lemann Index (LI), and to identify the associated factors. Methods A retrospective study was conducted involving all patients with CD followed in our center over a period of 4 years (2016- 2020), and who were evaluated by endoscopy and MRI at baseline. The Lemann Index is a score that measures cumulative damage to digestive tissue from entero-MRI and endoscopy data. A LI score &amp;gt; 2.0 was set as a cutoff to define advanced bowel injury. Hypothesis tests were applied to identify associations. Results 112 patients with CD were included in this study, of which 53.6% were female. The mean age at diagnosis was 33.29 years [15–63]. Regarding the localization of CD, it was ileal, colonic, and ileocolonic in respectively 16.1%, 42.9% and 41%. The disease phenotype was inflammatory in 60.7%, stricturing in 21.42%, and penetrating in 17.85%. The initial flare was judged to be severe in 33.9%, moderate in 55.4% and mild in 10.7% of cases, with a mean CDAI of 305.21 [115–493]. 12 patients had already undergone bowel resection. As for the biological data, the mean value of C-Reactive Protein (CRP) at the time of diagnosis was 74.08 +/- 54.05 mg / l, and that of the sedimentation rate (ESR) was 62, 13 +/- 36.49 (the 1st hour). The mean LI was 3.14 (± 2.28) with 64 patients (57.1%) presenting an LI score indicating advanced bowel injury at diagnosis. In univariate analysis, the factors associated in a statistically significant way, with a more important Lemann Index were: the male sex (p = 0.037), the history of intestinal resection (p = 0.009), a severe initial flare (p = 0.049). Similarly, a strong correlation was observed with the initial CDAI score (p = 0.024, r = 0.05) and the initial value of ESR (p = 0.001, r = 0.01). In addition, the duration of symptoms, age at diagnosis, initial disease location and phenotype, presence or absence of anoperineal manifestations, and CRP value at diagnosis were not correlated to the degree of intestinal destruction according to the LI score, with respectively: p = 0.43, p = 0.12, p = 0.19, p = 0.49, p = 0.34 and p = 0.063. Conclusion In our series, advanced intestinal lesions are present at the time of diagnosis in a significant proportion of patients. Thus, the use of the Lemann score from the diagnosis of Crohn’s disease is necessary.

P049 Should the Gallbladder be Empirically Removed at Time of Intestinal Resection in Inflammatory Bowel Disease Patients?

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract, which include Crohn's disease (CD) and ulcerative colitis (UC). Biliary complications are common amongst IBD patients. Up to 25% of patients with UC undergo colectomy and 50-75% of those with ileocolonic CD undergo intestinal resection. In this study, we aim to assess the prevalence of biliary disease (including cholelithiasis, cholecystitis, choledocholithiasis, cholangitis, and biliary pancreatitis) in IBD patients who have had intestinal resection compared to non-IBD patients who also have had intestinal resection. Our study may inform clinical practice in the need to empirically perform a cholecystectomy in IBD patients who undergo intestinal resection. METHODS: This is a retrospective single-institution chart review of IBD and non-IBD patients with a history of intestinal resection. All adult patients, >18 years of age, who underwent an intestinal resection surgery between January 1, 2010 and December 31, 2017 were included in this study. Patients who had a cholecystectomy or presence of gallstones prior to intestinal resection were excluded from this study. For patients meeting inclusion criteria, demographic characteristics, as well as presence of IBD, and subtype of IBD were included from the patient’s medical records. Development of subsequent biliary disease, after intestinal resection, was identified via review of the medical records with special attention to abdominal imaging reports and operative reports. RESULTS: A total of 370 patients with intestinal resection were identified and included in the study. Of those patients, 20 (5.4%) had IBD: 6 with UC and 14 with CD. The 6 UC patients underwent intestinal surgery due to medically refractory disease. Of the 14 CD patients, 12 patient (85%) had surgery for inflammatory complications (including inflammatory masses, strictures and fistulas), only 1 patient (7%) underwent surgery for medically refractory disease, and another patient (7%) had surgery due to a right colonic adenocarcinoma. The majority of our IBD patients were males (85% of CD, 66% of UC). The majority of CD patients (85%) underwent ileal/ileocecal resection, with only 2 patients (14%) had a right hemicolectomy, whereas most UC patients (80%) underwent subtotal colectomy, with only 1 patient (16%) who underwent a total colectomy. Two out of the 20 IBD patients (10%) and 42 out of the 350 non-IBD patients (12%) developed gallstones after intestinal resection (P = 1.0). None of the IBD patients developed post-intestinal resection cholecystitis, cholangitis, choledocholithiasis or biliary pancreatitis compared to the ten, four, four and one non-IBD patients who did develop these complications respectively. There was no difference in numbers of cholecystectomy post-intestinal resection between non-IBD and IBD patients [34(9.7%) vs 2 (10%); P-value = 0.71]. CONCLUSION: Although our numbers are small, presence of IBD was not a significant risk factor for the development of biliary complications after intestinal resection. Our data shows that performing a cholecystectomy at the time of intestinal surgery is not warranted.

Temporal trend of disease recognition, treatment paradigm, and clinical outcomes of Crohn disease in Thailand from 2000 through 2017: Is early use of thiopurines beneficial?

The prevalence of Crohn disease (CD) is increasing in Asia, but data from Southeast Asian population are scarce.The databases of 2 university-based national tertiary referral centers located in Bangkok, Thailand, were retrospectively reviewed for adult patients diagnosed with CD during January 2000 to December 2017. Disease characteristics, diagnosis, treatment, and outcomes were described and compared between the 2000 to 2009 cohort (cohort A) and the 2010 to 2017 cohort (cohort B).One hundred eighty-two patients (mean age: 46.4 years, 50% male) with 993 patient-years of follow-up were included. Thirteen percent had a history of intestinal resection, but were not diagnosed until disease recurrence. Another 6% were diagnosed at the time of first surgery. There was no improvement in diagnostic proficiency between cohorts. Mesalamine, corticosteroids, thiopurines, and biologics were prescribed in 75.8%, 81.3%, 84.6%, and 13.7% of patients, respectively (P > .05 between cohorts). Notably, thiopurines were started earlier in cohort B. Median time to the start of thiopurines was 6.2 and 1.65 months in cohort A and B, respectively (P < .01). However, the cumulative 5-year rates of disease behavior progression (P = .43), hospitalization (P = .14), and bowel surgery (P = .29) were not significantly different between cohorts. Subgroup analysis including only patients who required thiopurines showed the early use of thiopurines to be associated with lower risk of intestinal surgery after diagnosis (hazard ratio: 0.30, 95% confidence interval: 0.11-0.85).Early disease recognition and early introduction of immunomodulators may prevent long-term complications and reduce unnecessary surgery in CD.

Normalization of long-term quality of life in Crohn's disease patients receiving ustekinumab.

ustekinumab is a fully human monoclonal antibody against IL-12/23, approved for induction and maintenance treatment of Crohn's disease (CD). Real-life data shows its true effectiveness in terms of clinical and endoscopic response. However, there is little information regarding health-related quality of life (HRQoL) in CD patients receiving ustekinumab. The main aim of this study was to define long-term clinical remission and HRQoL normalization. The clinical predictive factors of clinical remission were investigated as a secondary aim. a retrospective, observational study was performed in CD patients under ustekinumab treatment in the Hospital Vall d'Hebron, between January 2009 and January 2019. Clinical remission was defined using the Crohn's Disease Activity Index (CDAI) and HRQoL normalization was defined by the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ). thirty-three patients were included. The average disease evolution was eleven years (standard deviation [SD]: 8), perianal disease was present in 13 patients (39 %), 30 patients (91 %) had previously been treated with alfa tumor necrosis factor antagonists (anti-TNF) agents and 22 patients (67 %) had a history of intestinal resection. Twenty-four patients (73 %) had undergone one year of treatment. Seventeen patients (51 %) reached clinical remission and six (18 %) restored the HRQoL. No predictors of clinical remission were identified. ustekinumab shows clinical effectiveness in real-life conditions similar to previous data. Normalization of HRQoL is low compared to clinical remission, which may be due to the inaccuracy of the indicator and the severe disease course. Such normalization is a challenge for physicians dealing with inflammatory bowel diseases.

680 Intestinal Resection and Clostridioides difficile Infection in Inflammatory Bowel Disease Patients: A Single Center Retrospective Cohort Study

INTRODUCTION: In inflammatory bowel disease patients (IBD), Crohn's disease carries a greater risk for surgical resection than ulcerative colitis (UC) through 10 years after diagnosis. Prior studies identify small bowel resection and colectomy as risk factors for the development of Clostridioides difficile infection (CDI). This study assessed the correlation between acquisition of CDI and timing of intestinal resection in IBD patients. METHODS: A retrospective cohort of patients age 18-75 with a history of IBD and a diagnosis of CDI from Jan 2012–Dec 31, 2016. Patient demographics, history of intestinal resection, and history of a single CDI or multiple CDI were reviewed. CDI index case was chosen as the infection with the closest timing to intestinal resection. Statistical analysis was performed with Chi-square testing. RESULTS: 121 IBD patients with CDI were identified. 48 patients (39.7%) underwent surgical resection (25 UC and 23 Crohn's). Of these, 16 patients had a single episode of CDI and 32 patients had a history of multiple CDI. CDI occurred prior to intestinal resection in 84% of UC patients and only 47.8% of Crohn's patients (P = 0.008). This relationship was mirrored in those with history of multiple CDIs (P = 0.006), but not for patients with history of a single CDI (P = 0.38). Within 1 month of surgical resection, there was no difference in the development of CDI for Crohn's compared to UC patients. However, in Crohn's patients with a history of multiple CDI, 77.8% experienced a CDI after a partial or total colectomy. CONCLUSION: In this cohort of IBD patients, CDI prior to surgery is more common in UC patients as compared to Crohn's. This likely reflects CDI's predilection for the colonic mucosa, which is altered by the pro-inflammatory state of UC. A history of CDI is not as common in Crohn's patients undergoing surgery likely due to decreased colonic involvement. Further investigation into CDI in Crohn's patients after colonic resection is warranted. This information may be used to guide therapeutic discussions with IBD patients who are diagnosed with CDI.

Clinical predictors of thiopurine-related adverse events in Crohn's disease.

To determine the incidence and predictors of thiopurine-related adverse events. Subjects with Crohn's disease who were followed in the Alberta Inflammatory Bowel Disease Consortium patient database registry were identified. Retrospective chart review was conducted between August 5th, 2010 and June 1st, 2012. We collected data on: age at diagnosis; sex; disease location and behaviour at time of prescribing thiopurine; perianal fistulising disease at or prior to thiopurine prescription; smoking status at time of thiopurine prescription, use of corticosteroid within 6 mo of diagnosis; dosage, age at onset, and cessation of 5-aminosalicyclic acid (5-ASA); anti-tumour necrosis factor medication exposure and intestinal resection before thiopurine prescription. The primary outcome of interest was the first adverse event that led to discontinuation of the first thiopurine medication used. Logistic regression models were used to associate clinical characteristics with outcomes after adjusting for potential confounders. Risk estimates were presented as odds ratios (OR) with 95% CI. Effect modification by age and sex were explored. Our cohort had a median follow-up duration of 5.8 years [interquartile range (IQR 25th-75th) 2.7-9.1]. Thiopurine therapy was discontinued in 31.3% of patients because of: hypersensitivity reactions (7.1%), acute pancreatitis (6.2%), gastrointestinal intolerance (5.4%), leucopenia (3.7%), hepatotoxicity (3.4%), infection (1.1%) and other reasons (4.3%). A higher incidence of thiopurine withdrawal was observed in patients over the age of 40 (39.4%, P = 0.007). A sex-by-age interaction (P = 0.04) was observed. Females older than 40 years of age had an increased risk of thiopurine discontinuation due to an adverse event (age above 40 vs age below 40, adjusted OR = 2.8; 95%CI: 1.4-5.6). In contrast, age did not influence thiopurine withdrawal in males (age above 40 vs below 40, adjusted OR = 0.9; 95%CI: 0.4-2.1). Other clinical variables (disease location and phenotype, perianal disease, smoking history, history of intestinal resection and prior 5-ASA or corticosteroid use) were not associated with an increased risk an adverse event leading to therapy cessation. Thiopurine withdrawal due to adverse events is commoner in women over the age of 40 at prescription. These findings need to be replicated in other cohorts.

Su1749 Intestinal Anastomotic Ulcers in Children With Short Bowel Syndrome and Anemia Detected by Capsule Endoscopy

Anastomotic ulcers are a known cause of anemia in children with a history of intestinal resection. The etiology of these ulcers may be secondary to ischemia or small bowel bacterial overgrowth (SBBO). Surgical resection may be required in the setting of anemia requiring multiple blood transfusions. Colonoscopy can be used to diagnose these ulcers. However, following serial transverse enteroplasty procedures (STEP), the area of involvement may be difficult to visualize with standard endoscopic techniques.

Factors Affecting Postoperative Recurrence in Japanese Patients With Crohnʼs Disease in The Era of Biologic Therapy: Retrospective Single Center Study

Because of the excellent short-term prophylactic effect of infliximab, anti-TNFα monoclonal antibody has been increasingly applied to postoperative patients with Crohn's disease (CD) in Japan. However, such application of biologics should be based on further clinical evidence. We thus investigated factors affecting postoperative recurrence of CD to ascertain longer prophylactic effect of anti-TNFα monoclonal antibody. Postoperative clinical course and endoscopic/radiographic findings of 44 patients with CD, who underwent curative ileal or ileocolonic resection, were retrospectively analyzed. Postoperative recurrence was determined based on endoscopic/radiographic findings, irrespective of clinical symptoms or laboratory data. Recurrence at the anastomotic site was defined by an endoscopic score >i2 of Rutgeerts' score or depiction of small barium flecks indicating erosion or ulceration, thickened mucosal folds, or intestinal narrowing under radiography. Recurrence was also regarded to be positive when active inflammatory lesions were detected outside the anastomotic site. Age, disease duration, history of intestinal resection, disease type, extent of disease, perianal disease, smoking habit, and postoperative treatments were also reviewed, and possible contribution of clinical factors to postoperative recurrence was analyzed. During the mean follow-up period of 29.6 ± 19.2 months, postoperative recurrence was defined to be positive in 23 of 44 patients. Active inflammatory lesions were detected in the anastomotic site in 13 patients, outside the anastomotic site in 6 patients, and both in 4 patients. Postoperatively, 23 patients were treated by scheduled infliximab (5 mg/kg, every 8 weeks) and 2 patients were treated by adalimumab (40 mg, every other week). Univariate analysis using Logrank test revealed that history of intestinal resection (P = 0.017) and current smoking habit (P = 0.007) were more frequent in patients with recurrence than in those without. In addition, recurrence was less frequent in patients with anti-TNFα monoclonal antibody than in those without (P = 0.006). Multivariate analysis using Cox proportional hazards model demonstrated that patients treated with anti-TNFα monoclonal antibody were less likely to recur (RR = 0.09. 95%CI; 0.02-0.34), while patients with history of intestinal resection had an increased risk of recurrence (RR = 8.54, 95%CI; 1.79-60.36). Anti-TNFα monoclonal antibody treatment after intestinal resection obviously improves postoperative clinical course in patients with CD. Postoperative prophylaxis by biologic therapy might be appropriate for patients requiring repeated surgery in consideration of their higher recurrence rate.

Sa1891 Long-Term Effect of Infliximab Against Postoperative Recurrence of Mucosal Lesions in Patients With Crohn's Disease

Background & Aims: It has been shown that infliximab (IFX) has short-term protective effect against postoperative recurrence in patients with Crohn's disease (CD), suggesting the role “reset” therapy for aggressive CD. However, long-term effect of IFX in postoperative CD remains to be elucidated. We aimed to investigate long-term effect of scheduled IFX against postoperative recurrence of intestinal lesions in patients with CD. Methods: Postoperative clinical course of 37 patients with CD, who underwent intraoperative enteroscopy (IOE) and ileocolonic resection, was retrospectively investigated. In each patient, endoscopic/ radiographic findings after surgery were reviewed. Recurrence at the anastomotic site was defined by an endoscopic score >i2 of Rutgeerts' score or by depiction of small barium flecks indicating erosion or ulceration, thickened mucosal folds, or intestinal narrowing under double-contrast barium enteroclysis. Recurrence outside the anastomotic site was regarded to be positive when active inflammatory lesions were endoscopically or radiographically detected in the intestinal segment where preceding IOE had not identified any active lesion. Age, disease duration, history of intestinal resection, disease type, extent of disease, perianal disease, active inflammatory lesions under IOE, smoking habit, and postoperative treatments were also reviewed. Results: 19 of 37 patients were treated by scheduled IFX (5mg/kg, every 8 weeks). 17 patients (46%) showed postoperative recurrence. Time interval between surgery and confirmation of recurrence was 26.9±18.7 months. 3 of 17 patients with recurrence were under IFX. Active inflammatory lesions were detected in the anastomotic region in 10 patients, outside the anastomotic region in 5, and both in 2. Univariate analysis revealed that history of intestinal resection (Log-rank test: p=0.047), penetrating disease (p=0.01), current smoking habit (p=0.039) and ileocolonic anastomosis (p=0.046) were more frequent in patients with recurrence than in those without. In addition, recurrencewas less frequent in patients with IFX than in thosewithout (p=0.014).Multivariate analysis revealed that patients treated with IFX were less likely to recur (Cox proportional hazards model: OR=0.08, 95% CI 0.009-0.43), while patients with history of intestinal resection had an increased risk of recurrence (OR=9.97, 95% CI; 1.71-98.1). Stratified analyses revealed that in patients treated by IFX, recurrence was less frequent in patients with concomitant immunomodulators than in those without, although the difference did not reach a statistical significance (0% vs. 21%, p=0.11). Conclusions: Scheduled IFX treatment after intestinal resection can exert a longer prophylactic effect in postoperative CD. Intensive postoperative treatment seems to be necessary for patients who require repeated surgery.

Vascular and Cellular Stress in Inflammatory Bowel Disease: Revisiting the Role of Homocysteine

Moderate hyperhomocysteinemia is a complex trait commonly associated with inflammatory bowel disease (IBD). Nutritional deficiencies and genetic determinants have been identified as risk factors for moderate hyperhomocysteinemia, such as folate and vitamin B(12) deprivation and polymorphisms in the 5,10 methylenetetrahydrofolate reductase (MTHFR) encoding gene, respectively. Homocysteine has a crucial role in cellular stress, epigenetic events, inflammatory processes, and host-microbial interactions. Hyperhomocysteinemia might therefore influence the clinical history of IBD, including disease severity, susceptibility to particular enteric infections, and the risk for the development of colorectal cancer. In contrast, homocysteine metabolism does not seem to contribute to the greater risk of thrombosis in IBD subjects. Herein, we review the evidence linking homocysteine metabolism to the pathophysiology of IBD. Furthermore, we discuss the relevance of screening and treating folate and vitamin B(12) deficiencies in IBD subjects. Given the peculiar frequency of such deficiencies in IBD, normalizing vitamin levels should be an integral part of the management of these patients, especially those with active disease, history of intestinal resection, and/or treated with methotrexate.

4484 Colonoscopic findings in intestinal behcet's disease.

Background: Behcet's disease is a multisystemic chronic inflammatory disease characterized by oral ulcer, genital ulcer, skin manifestations and ocular involvements as major symptoms. Minor symtoms include arthritis or arthralgia, vascular lesion, CNS involvement, epididymitis, and intestinal ulcers. Intestinal involvement in Behcet's disease is not rare in Korea. Ulceration can occur in any part of the gastrointestinal tract including the esophagus, stomach and duodenum, but the ileo-cecal area is the most commonly involved site. Aim: The aim of this study was to characterize the colonoscopic findings of intestinal Behcet's disease. Methods: We retrospectively reviewed colonoscopic examinations in 92 patients with intestinal Behcet's disease. Among 92 patients, complete, incomplete, suspicious, and possible types included 16, 26, 24, and 18 cases, respectively. The remaining 8 cases did not have any major systemic manifestation of Behcet's disease. About 2/3 of the patients were diagnosed as Behcet's disease before intestinal involvement was identified. Twenty-four (26%) patients had a previous history of intestinal resection at the time of colonoscopy. Results: Abdominal pain (94%) was the most common symptom, followed by diarrhea (30%), melena/hematochezia (25%), weight loss, fever, indigestion and nausea/ vomiting. Colonoscopy demonstrated ulcerative lesions in all cases. Among patients who did not have operations, ileo-cecal area was the most commonly involved site (92%). Seven (8%) patients had ulcers in other parts of the colon. All of the operated patients had ulcers at the ileo-colonic anastomostic site. Most (95%) of the ulcers were round/oval or geographic in shape while longitudinal or circumferential ulcers were rare (5%). Sixty-one patients (66%) had a single ulcer, 19 (21%) had several (2-5) ulcers, and 12 (13%) had multiple (≥6) ulcers. The ulcer was small (≤ 10 mm) in 20 patients (22%), medium-sized (11-20 mm) in 20 (22%), and large (>20 mm) in 52 patients (57%). Mean size of ulcer was 3.0 cm. The ulcer was deep in 56 patients (61%) while shallow in 36 (39%). The margin of ulcer was discrete in 75 cases (82%), elevated and nodular in 56 cases (62%), and erythematous in 48 cases (52%). Mucosal changes adjacent to the ulceration such as erhthema and edema were not common, and were noted in 22 cases (24%). Conclusion: Typical colonoscopic finding in intestinal Behcet's disease included a single or a few deep ulcers with discrete margin and normal adjacent mucosa in the ileocecal area or ileo-colonic anastomotic site.

Serum n3 polyunsaturated fatty acids are depleted in Crohn's disease.

To determine fatty acid patterns in Crohn's disease, we measured various serum fatty acids by gas chromatography in 20 patients with the disease and compared them with those in 18 healthy controls. All the patients had been free from any nutritional supplementation during preceding six months or had no history of intestinal resection. Eight of the patients were affected in the small bowel only, three in the large bowel only, and the remaining nine in both the small and large bowel. Both serum concentrations and percentages of C20:4n6, C20:5n3, C22:0, C22:6n3, total n3 polyunsaturated fatty acids, and total polyunsaturated fatty acids were lower in the patients than in the controls. Both essential fatty acids (C18:2n6, C18:3n3) and C20:3n9 levels were not different between the two groups. Among nine fatty acids that correlated with the Crohn's disease activity index, C20:5n3 and total n3 polyunsaturated fatty acids showed the most significant negative correlations. These findings suggest that essential fatty acid deficiency rarely occurs in Crohn's disease and also that n3 polyunsaturated fatty acids may be relevant to the activity of the disease.

Late sequelae of blind intestinal pouches

Five case histories are presented which point out the complications of side to side intestinal anastomosis. In these instances a blind pouch was the sole cause of a variety of clinical problems. The difficulties in establishing an early correct diagnosis are understandable but not necessarily acceptable. Although isolated case reports reach the literature, it is indeed likely that the increasing use of end to end anastomoses will relegate these pouches to the position of actuarial oddities. It must be remembered, however, that the lateral anastomoses employed years ago remain potentially dangerous and may be the causes of many bizarre and longstanding abdominal complaints. An awareness of the possibility of a pouch in a patient with a history of intestinal resection, particularly if operated on a decade or so ago, could lead to early surgical intervention and replacement of the lateral anastomosis with an end to end anastomosis. Five case histories are presented which point out the complications of side to side intestinal anastomosis. In these instances a blind pouch was the sole cause of a variety of clinical problems. The difficulties in establishing an early correct diagnosis are understandable but not necessarily acceptable. Although isolated case reports reach the literature, it is indeed likely that the increasing use of end to end anastomoses will relegate these pouches to the position of actuarial oddities. It must be remembered, however, that the lateral anastomoses employed years ago remain potentially dangerous and may be the causes of many bizarre and longstanding abdominal complaints. An awareness of the possibility of a pouch in a patient with a history of intestinal resection, particularly if operated on a decade or so ago, could lead to early surgical intervention and replacement of the lateral anastomosis with an end to end anastomosis.