Complicated Crohn Research Articles

Minimal Open Access Ileocolic Resection in Complicated Crohn's Disease of the Terminal Ileum.

The objective of this study was to evaluate the possibility to undertake an ileocolic resection in complex Crohn's disease using a minimal open abdominal access using standard laparoscopic instruments. The incision was carried out over the previous McBurney scar, with a mean length of 6 cm. Seventy-two patients with complicated Crohn's disease underwent IC resection in the considered period; 12 patients had a McBurney scar due to a previous appendectomy and represented the group of study. Feasibility and safety of the procedure were evaluated. Clinical data and outcome were compared with a control arm of 15 patients who had a standard laparoscopic IC resection, pooled out from our database among those who had a McBurney incision as service incision. Mean operative time and postoperative stay were significantly shorter in the study group. Blood loss and operative costs were also lower in the study group but did not reach statistical significance. Minimal open access ileocolic resection (MOAIR) through a small McBurney incision seems safe and feasible in complex Crohn's disease. Some advantages over standard laparoscopic surgery could be found in surgical outcomes and costs.

A36 THE ROLE OF MICROBIAL INDOLE METABOLITES IN CONTROLLING INFLAMMATORY RESPONSES AND HEALING IN RESPONSE TO DSS-INDUCED COLITIS

Abstract Background Failure to resolve inflammation is often associate with the complications of Crohn’s Disease (CD). The pregnane X receptor (PXR), a xenobiotic receptor, is recognized for its role in suppressing inflammation and has recently been shown to influence fibrogenesis in the liver. In the intestine, PXR-signaling can be influenced by the microbial tryptophan metabolite indole-3- propionic acid (IPA), which can modulate intestinal inflammation, in turn influencing fibrogenesis, resolution and healing. This suggests that the gut microbiota could modulate mucosal homeostasis and resolution of inflammation via microbial metabolites Aims To understand and characterize the interplay between microbial complexity and the regulation of host inflammatory and healing responses, specifically focusing on the PXR and its microbial metabolite ligand IPA. Methods Intestinal inflammation was induced using DSS (1%, 1.5%, 2% and 3.5%) for 5 days followed by healing for 25 days in C57Bl/6 stably derived moderately diverse mouse microbiota 2 (sDMDMm2) colonized gnotobiotic and C57Bl/6 specific pathogen free (SPF) mice. Inflammation, architectural changes and fibrosis were assessed using Haemotoxylin and Eosin and Masson-Trichrome histological stains. Weight was recorded daily for the first 10 days and every other day after for 25 days, for a total of 30 days. Fecal lipocalin was quantified in samples collected throughout the study to assess inflammation. Innate immune cell influx was measured by flow cytometry, and the microbiota assessed via 16S rRNA sequencing. Results The gnotobiotic sDMDMm2 mice were exquisitely sensitive to DSS-induced colitis, exhibiting significantly increased mortality and morbidity at 2% and 3.5% w/v DSS compared to the SPF group. To elicit the same degree of disease to assess recovery, sDMDMm2 mice were exposed to 1.5% DSS and SPF mice to 3.5% DSS. Following 25 days recovery, sDMDMm2 colonized mice showed increased levels of fecal lipocalin 2, as compared to the SPF mice. DSS-treated sDMDMm2 mice supplemented with IPA during their recovery presented lower levels of fecal lipocalin, similar to colitic SPF mice. IPA supplemented sDMDMm2 mice also exhibited greater overall survival, with no significant differences in neutrophil count compared to mice given H20 during recovery. Conclusions A model system with a less complex microbiota (sDMDMm2) has a higher susceptibility to acute inflammation and a diminished capacity to resolve said inflammation. Addition of the microbial metabolite IPA normalized the recovery of the sDMDMm2 colonized mice, to a response indistinguishable from SPF mice, while also increasing survival. These data highlight the importance of microbial complexity in the regulation of intestinal mucosal homeostasis. Funding Agencies CAG, CCC, CIHR

Levels of Intestinal Inflammation and Fibrosis in Resection Specimens after Preoperative Anti-Tumor Necrosis Factor Alpha Treatment in Patients with Crohn's Disease: A Comparative Pilot Study.

Background Strictures are a common complication in Crohn's disease (CD), found in more than 50% of patients. They are characterized by the excessive deposition of extracellular proteins in the tissue as a result of the chronic inflammatory process. The effect of anti-tumor necrosis factor alpha (TNF-α) therapy on the development of fibrosis is not yet fully understood. Aim To investigate whether the degree of intestinal inflammation and fibrosis is correlated with preoperative anti-TNF-α) therapy on the development of fibrosis is not yet fully understood. Methods This unblinded, prospective, single tertiary center, pilot cohort study included all adult patients with CD who underwent elective, laparoscopic, or open intestinal resection. Preoperative investigations included measurement of blood TNF-α) therapy on the development of fibrosis is not yet fully understood. Results Histopathological specimens from 10 patients with CD who underwent ileocecal or ileocolic resections were retrieved. Four of those patients were on anti-TNF-α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. p=0.01). Anti-TNF-α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. Conclusions Patients who underwent preoperative anti-TNF-α treatment had a higher fibrosis score than controls.α) therapy on the development of fibrosis is not yet fully understood.

Magnetic resonance enterography in inflammatory small bowel disease. image analysis criteria

Today magnetic resonance enterography is one of the most informative and safe methods of identification of the manifistations and complications of Crohn’s disease among children and adults. Receipt of the high-informaitive MR-enterograms directly depends on the right preparation of the patient and the competent research. The article deals with semiotics of the small bowel lesions in Crohn’s disease. The qualitative and quantitative analysis of the images are also represented.

P176 Expert consensus on acquisition and reporting of intestinal ultrasonography activity in Crohn’s disease. A prospective inter-rater agreement study

Abstract Background Intestinal ultrasonography (IUS) is a promising cross-sectional imaging modality used to assess transmural disease and complications in Crohn’s disease (CD). Although recently positioned as a first-line modality for evaluation as per ECCO guidelines, standard measurements, reproducibility and nomenclature have not yet been clearly established. The aim of this study was to evaluate the inter-rater agreement for parameters identified as important by experts through Delphi consensus. Methods IUS parameters demonstrating inflammatory activity were systematically reviewed in the literature and presented to IUS experts. Individual parameters were selected by a blinded Delphi consensus panel to establish relative contribution to inflammatory activity in CD. Weighted grading of each parameter was further established by expert consensus. Image acquisition for optimal measurement was established by consensus. Two phases for evaluating inter-rater variability were undertaken. Phase 1: blind review by 8 readers of 20 de-identified CD cases. Cases with poor agreement were reviewed to clarify discrepancy and improve agreement. Phase 2: an additional 30 de-identified CD cases blindly were reviewed by 12 independent expert readers. Inter-rater agreement was evaluated for all 4 key parameters. Statistics were performed using Stata 16. Bowel wall thickness (BWT) was assessed using intraclass correlation coefficient (ICC) and the ordinal parameters using weighted Cohens Kappa. Results The Delphi process reduced 12 activity parameters to 4 key contributors including BWT, color Doppler signal (CDI), inflammatory fat and bowel wall echostratification (Figure 1). BWT was regarded as pathologic if the average of 4 measurements were > 3 mm for the small and large bowel, and grades of the additional parameters established (Table 1). Bowel wall thickness was comprised of 2 measurements in cross section and 2 in longitudinal orientation (Figure 2). Interobserver agreement was almost perfect for BWT: ICC=0.91 (95% CI 0.83 to 0.96) p = 0.001, while there was moderate agreement for CDI κ=0.60 (95% CI 0.48–0.72) p = 0.001. Agreement for inflammatory fat detection was also moderate with κ= 0.50 (95% CI 0.33–0.66) p = 0.001, while stratification was fair κ= 0.39 (95% CI 0.26–0.53) p = 0.001. Conclusion This expert consensus-based IUS activity score clearly establishes the reproducibility of this standardised approach to measure inflammatory activity in patients with CD. Using our method, BWT which is known as the most important parameter, is highly reproducible with CDI and inflammatory fat demonstrating moderate reproducibility. This score may provide the foundation for the future incorporation of IUS in research studies and clinical trials.

DOP85 The role of fibroblasts in the pathogenesis of Crohn’s disease-associated fistulas and in mesenchymal stem cell therapy

Abstract Background Perianal fistulas are a severe and frequent complication in Crohn’s disease (CD) patients, significantly affecting their quality of life. High recurrence rates, incomplete fistula healing and non-responding patients make the treatment challenging. Despite some novel insights, current knowledge about the pathogenesis of fistula formation is still limited. Fibroblasts are abundantly present in CD fistulas and were recently reported to regulate Th1 cell activity in inflammatory bowel disease (IBD) (Beswick EJ et al. 2018). We hypothesised that fibroblasts act as the key drivers of fistula pathogenesis by regulating inflammatory cell recruitment. Methods Fibroblasts were isolated from curettage material of perianal CD fistulas, non-CD-associated fistulas, and the normal colon (obtained at surgery for colorectal cancer at least 10 cm away from the primary tumour). For all experiments, fibroblast populations were identified by qPCR and flow cytometry analysis first. Then gene expression profiling via mRNA sequencing of cultured fistula- and colon-derived fibroblasts was performed. The characterisation was complemented by flow cytometry analysis. Furthermore, the interaction of fistula-derived fibroblasts with regulatory T cells (Tregs) was studied in co-culture experiments. Results mRNA sequencing analysis revealed no significant differences in gene expression between perianal CD fistulas and non-CD-associated fistulas. However, comparing fistula-derived samples to fibroblasts derived from the normal colon, we found over 6000 significantly differentially expressed genes. Among the 20 most significant differentially expressed genes between CD fistulas and colon fibroblasts were genes related to epithelial-mesenchymal transition, cell migration or the NF-κB signalling pathway. Furthermore, co-culture experiments with CD fistula-derived fibroblasts, revealed increased proliferation rates of CD25+FoxP3+ Treg cells. In addition, more CD4+ T cells differentiated into Treg cells after exposure to CD fistula fibroblasts. Conclusion Our data indicate a pathogenic role of fibroblasts located in the fistula tract. Their gene expression profile markedly differed from fibroblasts derived from the normal part of the colon. Based on our data, there is no difference between CD-associated and non-CD-associated fistula fibroblasts. CD fistula-derived fibroblasts seem to increase both the proliferation of Treg cells, and the differentiation of CD4+ T cells into Treg cells, indicating an important immunoregulatory role of fibroblasts. Ongoing experiments should reveal which cytokines and chemokines are involved in this process.

P161 Intra-abdominal abscess in Crohn’s disease

Abstract Background Crohn’s disease (CD) is associated with the emergence of complications, including intra-abdominal abscess. Management is multidisciplinary based on close medical-surgical collaboration. The aim of the study was to evaluate the clinical characteristics, the efficacy of different therapeutic options of intra-abdominal abscess in CD patients and to identify predictive factors of a favorable response. Methods Medical records of 56 CD patients who had intra-abdominal abscess were retrospectively reviewed. Patients with postoperative abscess were excluded. Clinical, biological and therapeutic data were retrospectively assessed. Treatment progression was appreciated.IBM SPSS software 21.0 was used for statistical analysis of our data. Results In total, 897 patients were identified as having CD in the study period, 56 of them developed intra-abdominal abscess. Means that the prevalence of intra-abdominal abscess in CD patients was 6,2%. Mean age was 35,24 ± 11,6 years old with a sex ratio M/F 0,64. 47,3% had penetrating CD. 50.9% of our patients were known to be carriers of Crohn’s disease, 45% of whom were on 5-ASA, while the remaining patients 49.1% (n = 26), the abscess was inaugural and revealing of the CD.The clinical signs were dominated by pain in 80%, the abscess was localised mainly at the right iliac fossa in 77.7% of cases. Median size of collection was 3,8 ± 2 cm. There were 47,3% patients who had fistula associated to abscess. The initial reactive C protein ranged from 14 to 320 (median 58.3) mg/L. All patients had first-line treatment based on broad-spectrum bi-antibiotic therapy, alone in 25.5%, combined with surgical resection in 45.5%, surgical abscess drainage without resection in 23,6% or guided by imaging in 5.5%, the initial success was 71.7%. 28.3% of patients underwent surgery for initial treatment failure, which was dominated by ileocecal resection in 53.1%. Overall success was 92.3%, only one death was noted following postoperative release with peritonitis. Predictive factor of favorable response was: fistula associated with intra-abdominal abscess (p =0.03) and surgical resection seems to be the best therapeutic option (p < 0,001). Conclusion Intra-abdominal abscess is a complication of Crohn’s disease (CD) mainly penetrating, in almost half of the cases, it can reveal CD. Our study showed that the presence of fistula appears to be significantly associated with therapeutic success and the best results are obtained in the case of surgical resection.

P383 The level of intestinal inflammation and fibrosis in resection specimens after preoperative anti-tumour necrosis factor-α treatment in patients with Crohn’s disease: a comparative pilot study

Abstract Background Strictures are a common complication in Crohn’s disease (CD), which are found in more than 50% of the patients. They are characterised by excessive deposition of extracellular proteins in the tissue as a result of the chronic inflammatory process. The effect of anti- TNF-α therapy on the development of fibrosis is not yet fully understood. The aim of the study was to investigate whether the degree of intestinal inflammation and fibrosis correlates with pre-operative anti-TNF-α therapy in patients with Crohn’s disease undergoing bowel resection. Methods This is an unblinded, prospective, multicentre cohort pilot study. All adult patients with Crohn’s disease, who underwent elective, laparoscopic or open intestinal resection were included. Pre-operative blood investigations included measurement of TNF- α concentration and specific drug antibodies in addition to the concentration of selected inflammatory cytokines. Three pathologists examined the specimens independently and assessed the degree of inflammation and fibrosis. Results Histopathological specimens from 10 patients with CD who underwent ileocecal or ileocolic resections were retrieved. Four of those patients were on anti-TNF-α treatment pre-operatively. The last dose of anti-TNF-α agents was administered within 1–9 weeks prior to bowel resection. Patients on anti-TNF-α treatment had higher fibrosis score than the controls (p = 0.01). Anti-TNF-α treatment was not associated with an increase in either CD68 or CD163-positive macrophages. There was no significant relationship between time from last anti-TNF-α dose to surgery, and fibrosis score. No significant association between the concentration of major inflammatory cytokines including TNF-α and fibrosis score or degree of inflammation was found. Conclusion Patients on anti-TNF-α treatment had higher fibrosis score than the controls.

P046 Vitamin D decreases PDIA3 and prevents the enhanced migration of fibroblasts from stricturing Crohn’s disease

Abstract Background Fibrosis is a common complication in Crohn’s disease (CD) patients and fibroblasts play an important role in the fibrogenic process. Low vitamin D (VD) levels and a defective VD-signalling pathway have been reported in CD. VD signals through both vitamin D receptor (VDR) and protein disulfide-isomerase A3 (PDIA3) and we have previously demonstrated that VDR protein levels are reduced in fibroblasts isolated from CD patients and that VD increased VDR expression in these cells (A-2080; ECCO 2019). We aim to analyse here the effect of VD on both PDIA3 protein levels and migration in CD fibroblasts. Methods We used intestinal fibroblasts isolated from surgical resections of the damaged mucosa of CD patients with stricturing behaviour (B2). Control fibroblasts were obtained from the non-damaged intestine of patients with colorectal cancer. Fibroblasts were treated with VD (100 nM) or its vehicle for 24 h and PDIA3 protein levels were measured by Western Blot. In the wound healing analysis, a single scraping was done in the centre of the fibroblasts monolayer and FBS-free medium was added to the cells, which allows us to determine the ability of fibroblasts to migrate and close the wound. Photos were taken at 0, 24 and 48 h. Results of wound healing were expressed as the percentage of the wound at each time point for the maximal wounded area (time 0, 100%). Statistical significance was measured by ANOVA or t-test. Results No significant differences in PDIA3 protein levels were detected between control and CD fibroblasts but VD significantly decreased PDIA3 expression in CD fibroblasts (Figure 1A). In the wound healing assay, we detected that CD-B2 fibroblasts migrate faster than control cells, resulting in a reduced wounding area, 48 h later (Figure 1B). Treatment of these CD-B2 cells with VD decreased their migration rate, and 48 h later cells exhibited a higher and significant wounding area than vehicle-treated cells (Figure 1C). Conclusion Vitamin D decreased PDIA3 expression and prevented the accelerated migration detected in intestinal fibroblasts from B2-CD patients which suggest an anti-fibrotic effect of VD mediated by a direct effect of this hormone on intestinal fibroblasts.

P032 Increased endoplasmic reticulum stress-specific chaperones characterise CD fibrosis epithelium tissues and participate to in vitro induction of intestinal fibrobast differentiation

Abstract Background Intestinal fibrosis is a complication of Crohn’s disease (CD) characterised by myofibroblasts and extracellular matrix accumulation within the submucosa and smooth muscles, leading to bowel strictures. No medical treatment exists to treat or reverse intestinal fibrosis leading often to surgical resection. The potential role of intestinal epithelium in the fibrotic process remains poorly defined. Methods We performed a pilot study on ileal fibrostricturing CD surgical samples (n = 5), comparing the proteome of surface epithelium isolated by laser capture microdissection in normal and fibrotic zones. Confirmation of the specific protein increases was obtained by immunohistochemistry in colonic and ileal samples of CD (n = 44) compared with healthy subjects (n = 40), as well as in intestinal epithelial cell line under induced endoplasmic reticulum (ER) stress. A model of fibroblast to myofibroblast differentiation induction was also challenged using preconditioned media of intestinal epithelial cells after a pulsed ER stress. Results Label-free proteomics revealed high ER stress in the epithelium surrounding fibrotic bowel wall, involving anterior gradient protein 2 homolog (AGR2) and 78 kDA glucose-regulated protein (BiP). Confirmation of both proteins increase was obtained by immunohistochemistry. ER stress induction in intestinal epithelial cells was associated with an intracellular increase of AGR2, BiP and ER stress markers as sXPB1 and CHOP. AGR2 was also detected in the culture medium of these epithelial cells and myofibroblast differentiation was obtained using this culture medium. Conclusion The increase of ER stress proteins observed in fibrostenosing tissues together with these preliminary evidences of fibroblast to myofibrobast differentiation obtained by paracrine action of intestinal epithelial cell preconditioned to ER stress induction suggest a role of epithelial ER stress in Crohn’s disease intestinal fibrosis.

P414 Risk factors for the development of anti-drug antibodies to infliximab and adalimumab in Crohn’s disease

Abstract Background Anti-tumor necrosis factor-α (anti-TNFa) therapy have been established as an effective maintenance treatment for complicated Crohn’s Disease (CD). However, the efficacy of Infliximab (IFX) and Adalimumab (ADM) may be affected by low serum levels and/or the presence of anti-drug antibodies (ADA). This reinforces the importance of therapeutic drug monitoring (TDM). We aim to assess the clinical benefit of proactive vs. reactive TDM. Secondly, to assess the impact of TDM on clinical management. Thirdly, to identify risk factors for low serum drug levels and the development of ADA in CD patients. Methods This was a single-centred observational cohort study performed at a tertiary hospital, comprising of total 229 CD patients: 142 received IFX and 87 received ADM, who have had a trough drug level, tested using enzyme-linked immunosorbent assay. Demographic and clinical data were retrospectively collected from electronic medical records. Fisher’s Exact Test was used to determine if there are nonrandom associations between variables. A p-value of less than 0.05 was considered statistically significant. Results One hundred and fourteen patients (49%) receiving a standard anti-TNFa regimen had subtherapeutic drug levels (67 had IFX < 3 μg/ml and 47 had ADM < 5 μg/ml). Interestingly, almost half of this cohort were asymptomatic. Reactive TDM completed among symptomatic patients have shown to have a statistically significant benefit in detecting subtherapeutic drug level (p = 0.0001). Following these results, only fifty-two patients (46%) had a change of therapy (29 IFX, 25 ADM); while the remaining sixty-two patients (54%) continued the same dosing regimen with only one documented admission within 90-days following the drug level being taken. Eight patients (4%) were found to have positive ADA, all in the presence of subtherapeutic drug levels. Two of these had a subsequent flare of their disease. They were all switched to another class of biologic therapy. Non-smoking status at diagnosis and the concomitant use of immunomodulator were found to have statistically significant associations with a therapeutic drug level (p = 0.0176 and p = 0.0001, respectively). Similarly, both of these risk factors were associated with lower risk of ADA formation (p = 0.0057 and p = 0.0165, respectively). Conclusion This study suggests that a large proportion of patients have subtherapeutic drug levels at standard dosing schedules. However, low drug levels do not correlate with a higher risk of complications if patients are in clinical remission. The results of this study also indicate that non-smoking status at diagnosis and the concomitant use of immunomodulator are associated with higher serum drug levels and lower risk of developing anti-drug antibodies.

Preoperative enteral nutrition in adults with complicated Crohn's disease: Effect on disease outcomes and gut microbiota

ObjectivesThe use of exclusive enteral nutrition (EEN) in patients with Crohn's disease (CD) before surgical resection can reduce disease activity and improve nutritional status. The mechanism of EEN action is unclear, but it might involve modulation of the intestinal microbiota. The aim of this study was to evaluate the effects (namely changes in gut microbiota) of preoperative EEN in adults with complicated CD referred to surgery. MethodsThis was a prospective study of adult patients with CD referred to surgery. Patients with body mass index <18.5 kg/m2, weight loss >10 %, serum albumin <3 g/dL, or a combination of some or all three, received EEN for ≥2 wk. The effects of EEN on clinical (Harvey–Bradshaw Index [HBI]) and laboratory markers (C-reactive protein [CRP], serum albumin, and fecal calprotectin) and fecal microbiota were analyzed after EEN (before surgery) and 6 mo later. We used 16 S rRNA gene sequencing to determine changes in the fecal microbiota. ResultsFifteen patients were included, of whom 60% were men with a mean age of 45.4 ± 19.1 y. Of those, 10 received EEN. The median duration of preoperative EEN was 41.5 d (15–70 d). During EEN, there was a significant reduction in mean HBI (8.7 ± 1.9 versus 4.1 ± 2.4; P = 0.001) and CRP (11.7 ± 10.3 versus 0.8 ± 0.8 mg/dL; P = 0.008) and an increase in serum albumin (3.1 ± 0.6 versus 4 ± 0.6 g/dL; P = 0.022). Two patients did not require surgery after EEN. The overall microbial composition changed after EEN (Permutational analysis of variance test, P = 0.046) and there was a significant reduction in α diversity (8 ± 2.3 versus 5.2 ± 1.5; P = 0.023). EEN significantly changed the relative abundance of 11 taxonomic operational units (OTUs). At the family level, we found this was mainly due to the decrease in the Enterobacteriaceae family (7 OTUs). Six months after surgery, α diversity was not different from that before or after EEN; at this time point 6 OTUs were significantly different, mainly due to the decrease of Clostridiales order (3 OTUs). The incidence of postoperative complications and hospital length of stay were similar in EEN and immediate surgery groups, as well as clinical and endoscopic recurrence rates 6 mo after surgery. ConclusionsPreoperative EEN improved disease activity and nutritional status in patients with CD referred to surgery. Despite being malnourished, patients given EEN did not have increased postoperative complications compared with well-nourished patients. During EEN, overall microbiota composition changed and α diversity decreased. EEN did not influence postoperative recurrence and gut microbiota 6 mo after surgery.

Sprue-Like Intestinal Disease Following Crohn’s Disease

A 48-yr old female was reviewed for ongoing symptoms of diarrhea and weight loss following a total colectomy for colitis. Pathological review of the surgical specimens revealed changes of Crohn’s colitis. Subsequent investigations after the colectomy revealed endoscopic evidence of duodenal mucosal scalloping, negative celiac serological studies and moderate to severe changes in villous architecture including crypt hyperplasia with complete villus atrophy and increased numbers of intra-epithelial lymphocytes. No changes were present in the distal small intestine. Over the course of almost a decade, measures directed towards symptom relief were effective. However, in spite of a strict gluten-free diet, repeated endoscopic biopsies of the proximal small bowel remained severely abnormal with persistent crypt hyperplastic villus atrophy. “Sprue-like” intestinal disease occurs in Crohn’s disease limited to the duodenum, mimicking biopsy changes of celiac disease and may represent a post-colectomy complication in Crohn’s disease.

P096 Cerebral Venous Thrombosis as a Complication of Crohn's Disease

BACKGROUND: Extra-intestinal complications of inflammatory bowel disease are extensive; one well-known but rare complication is the development of thrombo-embolism. Most frequently reported events involve pulmonary or peripheral venous thromboses. We report an unusual case of cerebral venous thrombosis in a female patient with Crohn’s disease. CASE: A 52-year-old female with past medical history significant for Crohn’s disease and migraines presented to the hospital with a chief complaint of sudden onset numbness and weakness in her right upper extremity. On the day of admission, she awoke at approximately 5AM with a 10/10 throbbing, frontal headache associated with nausea &amp; photophobia. She went back to sleep and awoke 3 hours later with arm weakness. CT brain without contrast showed an extensive thrombosis of the superior sagittal sinus and bilateral cortical veins with associated intraparenchymal hemorrhage of the left frontal lobe. CT angiography (CTA), magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) of the brain, performed subsequently, re-demonstrated the prominent sagittal sinus thrombosis with involvement of the right transverse and sigmoid sinuses and mild propagation of the thrombus into the straight sinus. She was started on IV heparin and neurosurgery was consulted. Her handgrip strength slowly improved to 4/5. Inflammatory pro-markers, ESR and CRP were elevated, supporting active Crohn’s inflammation. Genetic testing for inherited thrombophilia were negative. She was ultimately discharged home with warfarin. DISCUSSION: Arterial and venous thrombo-embolic events are well documented and sometimes life-threatening complications of inflammatory bowel disease. Cerebral venous thrombosis has been reported rarely, but more often in association with ulcerative colitis than Crohn’s disease. Although the exact mechanism is unknown, the synergistic effects of an inflammatory state combined with transient elevation of coagulation factor levels, endothelial vascular activation, acquired natural anticoagulant deficiencies, increased platelet activation, and increased platelet aggregation have been shown to contribute to the prothrombotic state. Overall, patients with IBD have an approximately 2-fold increased risk for venous thrombo-embolism than the general population (RR, 1.96; 95% CI, 1.67-2.30), and account for 1.6% of all patients with central venous thrombosis. Early recognition and high suspicion of this condition for patients with IBD can help decrease mortality and prevent devastating complications such as hemiparesis, seizures, hydrocephalus, visual loss and dural arteriovenous fistulas. The optimal duration of anticoagulation and the risk for recurrent thrombosis are unclear in this population. Treatment merits careful coordination between gastroenterology, hematology, and neurology.

P050 Endoscopic Balloon Dilation of Crohn's Disease Strictures With or Without Fluoroscopic Guidance

BACKGROUND: Strictures are common complications in Crohn’s disease (CD). CD-associated strictures are usually managed with medical, endoscopic, and surgical approaches, or combinations. Endoscopic therapy is easier to perform in experienced hand and helpful to avoid the need for surgery. In clinical practice, endoscopic balloon dilatation (EBD) under a fluoroscopic guidance is preferred. The use of fluoroscopy allows for the delineation of the stricture and the orientation of the entire balloon catheter. The use of fluoroscopy exposes the patient, the endoscopist, and the endoscopy nurses to excessive radiation. EBD is performed without fluoroscopic guidance in some cases. However, the benefit of fluoroscopic guidance for dilating CD strictures has not been readily demonstrated. The hypothesis of the study is that there are no significant differences in efficacy and safety between EBD with and without fluoroscopic guidance for CD strictures. The aim of this study is to compare efficacy and safety between EBD with and without fluoroscopic guidance for CD strictures. METHODS: We performed a retrospective review of EBD for CD strictures between 2016 and 2017. We investigated the technical success and clinical success as the efficacy in EBD with and without fluoroscopic guidance for CD strictures. Technical success was defined as the ability to pass the scope through the stricture after balloon dilation. Clinical success was defined as improved obstructive symptoms. RESULTS: A total of 43 patients with CD strictures were identified (11 at EBD with fluoroscopic guidance group and 32 at EBD without fluoroscopic guidance group). Technical success was achieved in 10 patients (90.9%) at EBD with fluoroscopic guidance and 32 patients (100%) at EBD without fluoroscopic guidance (P = 0.084). Clinical success was achieved in 4 patients (36.4%) at EBD with fluoroscopic guidance and 18 patients (56.2%) at EBD without fluoroscopic guidance (P = 0.255). Additional surgery was performed in 4 patients (36.4%) at EBD with fluoroscopic guidance and 8 patients (25.0%) at EBD without fluoroscopic guidance (P = 0.469). Secondary EBD was performed in 2 patients (18.2%) at EBD with fluoroscopic guidance and 6 patients (18.8%) at EBD without fluoroscopic guidance (P = 0.967).There were no serious complications in both groups. CONCLUSION(S): There were no significant differences in efficacy and safety between EBD with and without fluoroscopic guidance for CD strictures. EBD guidance for CD strictures could be safe and effective in the setting without fluoroscopic guidance.

P092 Colo-Gastric Fistula as an Uncommon Complication of Crohn's Disease: A Case Series

P092 Colo-Gastric Fistula as an Uncommon Complication of Crohn's Disease: A Case Series

Stoma formation for Crohn’s disease in the post‐biologic era, Ma et al.

Up to one-third of patients with Crohn’s disease will require major abdominal surgery over the first 5 years of their disease and most Crohn’s patients will have a Crohn’s related operation at some time in their lifetime 1. Nonetheless, as surgeons we notice a trend towards less referrals for operations for Crohn’s disease, where the patients tend to present later and often in a poorer condition. It has been suggested that this change in surgical practice is due to the introduction of biologic medications for Crohn’s disease in the first half of the 2000s. However, despite the increasing use of novel biologic agents, counterintuitively the incidence of Crohn’s disease related surgery does not appear to be reducing 2. A recent large population based cohort study from Alberta, Canada, showed a decrease in emergency surgery but an increase in elective surgery 3. This might explain why surgeons get the sense that the burden for Crohn’s related surgery is less. One could expect that more elective surgery is related to earlier referral, a better condition of the patient at the time of surgery and therefore less stoma formation. In this month’s Editor’s choice study, Ma et al., from the same Canadian group, are looking at trends in stoma formation after the introduction of biologics in management of Crohn’s disease 4. In order to assess the need for stoma creation in the biological era, the authors queried an administrative population database from their area, serving 1.4 million inhabitants. They identified 545 patients who underwent bowel resection and stoma formation for Crohn’s disease between 2002 and 2011. They found a time based reduction in stoma rates from 2.30 stomas per 100 person-years to 1.51 stomas per 100 person-years. The number of emergency and temporary stomas decreased over time, whereas the number of elective permanent stomas remained stable. Except for severe perianal fistulising disease, elective stoma formation for Crohn’s disease becomes necessary where primary anastomosis is technically impossible or if there is a high risk for anastomotic breakdown. Unfortunately, this study was not able to identify the reason the stoma was indicated 4. Well-known risk factors for anastomotic complications in Crohn’s patients include recurrent clinical episodes, steroid use, and malnutrition 5. Nowadays, gastroenterologists have a wide range of medical therapies available to avoid intestinal resection. This might cause a delay to progress to surgery, which may result in a progressively more complex disease phenotype at the time of surgery. If this delay occurs, the patient’s condition deteriorates, and this forces the surgeon to elect for a stoma to avoid an anastomotic complication. The study by Ma et al. reminds us of the importance of appropriate and timely surgery, especially in the biologic era. Therefore, the IBD surgeon should be involved in the management of the Crohn’s patient from the first onset of the disease, as a member of an IBD multidisciplinary team.

Risk factors for recurrence after bowel resection for Crohn's disease.

BACKGROUNDComplications of Crohn’s disease such as intestinal obstruction, fistula or perforation often need surgical treatment. Nearly 70%-80% patients with Crohn’s disease would receive surgical treatment during the lifetime. However, surgical treatment is incurable for Crohn’s disease. The challenge of recurrence postoperatively troubles both doctors and patients. Over 50% patients would suffer recurrence postoperatively. Some certain risk factors are associated with recurrence of Crohn’s disease.AIMTo evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn’s disease.METHODSPatients diagnosed Crohn’s disease and received intestinal resection between April 2007 and December 2013 were included in this study. Data on the general demographic information, preoperative clinical characteristics, surgical information, postoperative clinical characteristics were collected. Continuous data are expressed as median (inter quartile range), and categorical data as frequencies and percentages. Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence, then log-rank test was applied to test the homogeneity of those clinical variables. Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence.RESULTSA total of 64 patients were included in this study. The median follow-up time for the patients was 17 (9.25-25.75) mo. In this period, 41 patients (64.1%) had endoscopic recurrence or clinical recurrence. Endoscopic recurrence occurred in 34 (59.6%) patients while clinical recurrence occurred in 28 (43.8%) patients, with the interval between the operation and recurrence of 13.0 (8.0-24.5) months and 17.0 (8.0-27.8) mo, respectively. In univariate analysis, diagnosis at younger age (P < 0.001), disease behavior of penetrating (P = 0.044) and preoperative use of anti-tumor necrosis factor (TNF) (P = 0.020) were significantly correlated with endoscopic recurrence, while complication with perianal lesions (P = 0.032) and preoperative use of immunomodulatory (P = 0.031) were significantly correlated with clinical recurrence. As to multivariate analysis, diagnostic age (P = 0.004), disease behavior (P = 0.041) and preoperative use of anti-TNF (P = 0.010) were independent prognostic factors for endoscopic recurrence, while complication with perianal lesions (P = 0.023) was an independent prognostic factor for clinical recurrence.CONCLUSIONDiagnostic age, disease behavior, preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn’s disease.

1575 Colouterine Fistula: A Rare Crohn's Complication

INTRODUCTION: Colouterine fistulas are a rare complication of gastrointestinal diseases, mostly described as a complication of diverticulitis in elderly patients. Colouterine fistula as a complication of Crohn's disease is exceptionally rare. We present a young Caucasian female with history of poorly controlled Crohn's disease presenting with colouterine fistula. CASE DESCRIPTION/METHODS: 26-year-old Caucasian female with ileal Crohn's disease since 2014 presented with abdominal pain and fever. Her PMH was significant for poor compliance with medications and follow ups. In the preceding 6 months she had a complicated clinical course including a flare with SBO and intraabdominal abscess while she was 23 weeks pregnant needing resection of TI and cecum with a diverting ileostomy followed 2 weeks later by a miscarriage, drainage of a perirectal abscess, fistula between loops of small bowel, and ileostomy take down followed by an abdominal wall abscess needing drainage. She had been lost to follow up and had not been on any medications the preceding one year. Her last colonoscopy was prior to ileostomy take down and had shown healthy appearing ascending colon stump, mild erythematous mucosa throughout the colon with no pathologic evidence of Crohn's and a well healing perianal fistula site. At presentation, ESR was 70 mm/h and CRP 81 mg/L. CT abdomen was read as a large peripherally enhancing fluid collection within the right lower abdomen and pelvis and mildly thickened neoterminal ileum. An abscessogram however showed the fluid collection was a large colouterine fistula filling the ascending colon at the anastomosis and both Fallopian tubes. Patient has been started on induction therapy with adalimumab and discharged with slow prednisone taper with plans to follow up for continued adalimumab therapy as well as evaluation at a facility with specialty Uro-Gynecology resources for fistula correction. DISCUSSION: Fistulas between small bowel and uterus in Crohn's disease has been described in literature. Fistulas between colon and uterus in Crohn's disease is exceptionally rare; to date only two cases have been reported, a sigmoid colouterine fistula and rectouterine fistula. The thick uterine wall is considered to be a protective factor against fistula formation, but prior colonic surgery or disruption of uterine wall integrity may predispose to fistula formation in Crohn's disease. Our patient had a recent ileocecectomy which was likely contributory to colouterine fistulization in the setting of poor compliance.

Anti-TNF and Postoperative Complications in Abdominal Crohn's Disease Surgery.

Biological therapy with anti-Tumour Necrosis Factor (TNF)-α agents revolutionised the treatment of inflammatory bowel disease over the last decades. However, there may be an increased risk of postoperative complications in Crohn's disease (CD) patients treated with anti-TNF-α agents prior to abdominal surgery. To evaluate the effects of preoperative anti-TNF-α therapy on the incidence of complications after surgery. A critical assessment of the results of clinical trial outcomes and meta-analyses on the available data was conducted. Based on the outcomes of previous reports including meta-analyses, preoperative use of anti- TNF-α agents modestly increased the risk of overall complications and particularly infectious complications after abdominal surgery for CD. Nevertheless, previous studies have several limitations. The majority of them were retrospective research with heterogeneous outcome measures and single centre trials with relatively small sample size. In retrospective studies, the standard protocol for assessing various types of postoperative complications was not used. The most serious limitation of the previous studies was that multiple confounding factors such as malnutrition, use of corticosteroids, and preoperative sepsis were not taken into consideration. Among patients treated with preoperative anti-TNF-α therapy, the risk of overall complications and infectious complications may slightly increase after abdominal surgery for CD. Nevertheless, the previous reports reviewed in this study suffered from limitations. To rigorously evaluate the risk of anti-TNF-α therapy prior to surgery, large prospective studies with standardised criteria for assessing surgical complications and with proper adjustment for confounding variables are warranted.