Perianal Crohn's Disease Research Articles

Surgical management of fistulating perianal Crohn's disease: a UK survey

Around one-third of patients with Crohn's disease are affected by Crohn's fistula-in-ano (pCD). It typically follows a chronic course and patients undergo long-term medical and surgical therapy. We set out to describe current surgical practice in the management of pCD in the UK. A survey of surgical management of pCD was designed by an expert group of colorectal surgeons and gastroenterologists. This assessed acute, elective, multidisciplinary and definitive surgical management. A pilot of the questionnaire was undertaken at the 2015 meeting of the Digestive Disease Federation. The survey was refined and distributed nationally through the trainee collaborative networks. National rollout obtained responses from 133 of 179 surgeons approached (response rate 74.3%). At first operation, 32% of surgeons would always consider drainage of sepsis and 31.1% would place a draining seton. At first elective operation, 66.6% would routinely insert of draining seton, and 84.4% would avoid cutting seton. An IBD multidisciplinary team was available to 87.6% of respondents, although only 25.1% routinely discussed pCD patients. Anti-tumour necrosis factor-alpha therapy was routinely considered by 64.2%, although 44.2% left medical management to gastroenterologists. Common definitive procedures were removal of the seton only (70.7%), fistulotomy (57.1%), advancement flap (38.9%), fistula plug (36.4%) and ligation of intersphincteric track (LIFT) procedure (31.8%). Indications for diverting stoma or proctectomy were intractable sepsis, incontinence and poor quality of life. This survey has demonstrated areas of common practice, but has also highlighted divergent practice including choices of definitive surgery and multimodal management. Practical guidelines are required to support colorectal surgeons in the UK.

Efficacy of adalimumab for Crohn's disease in real clinical practice

To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn's disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. The findings demonstrate the efficacy and safety of ADA used in clinical practice.

Perianal Crohn's disease: challenges and solutions.

Perianal Crohn’s disease affects a significant number of patients with Crohn’s disease and is associated with poor quality of life. The nature of the disease, compounded by presentation of various disease severities, has made the treatment of perianal Crohn’s disease difficult. The field continues to evolve with the use of both historical and contemporary solutions to address the challenges associated with it. The goal of this article is to review current literature regarding medical and surgical treatment, as well as the future directions of therapy.

N802 Improving care for patients with perianal Crohn's disease; review of a perianal virtual clinic

Background: Effective communication within the inflammatory bowel disease (IBD) team is essential to the management of perianal Crohn's disease (PCD). We identified that medical, nursing and surgical care could be fragmented for patients with complex PCD. To address this we developed the perianal vi

P245 A systematic review of outcomes reported in studies on fistulising perianal Crohn's disease

P245 A systematic review of outcomes reported in studies on fistulising perianal Crohn's disease

P672 Surgical and anti-TNFs combined therapy prevents Crohn's perianal fistula recurrence: a systematic review and meta-analysis

Background: The management of perianal Crohn's disease (CD) fistula represents a significant challenge. We aimed to conduct a meta-analysis to evaluating the efficacy and safety of combined surgical and anti-TNFs treatment compared with either single therapy in fistulising perianal CD. Methods: MEDLINE, EMBASE and the Cochrane database were searched. The primary outcome was the number of patients who developed fistula closure as defined by the primary studies. Results: Eight studies (3 prospective studies and 5 retrospective studies) invoving 688 patients were included. The rate of fistula closure of the combination therapy (78.5%, 197/251) was not significant higher compared with the surgical therapy alone (65.2%, 215/330) (OR 2.21, 95% CI 0.83–5.90, p=0.11). Similarly, neither the rate of complete closure nor the rate of partial closure was significantly different between the two groups. Significant lower proportion of patients in the combination group developed fistula recurrence (20.8%, 11/53) compared with the single surgical group (76.1%, 35/46) (OR 0.13, 95% CI 0.03–0.58; p=0.007). No significant difference observed between the combination therapy and anti-TNF therapy alone in the rate of fistula closure. However, the combination therapy was associated with a 76% risk reduction of fistula recurrence (OR 0.24, 95% CI 0.06–0.93, p=0.04, n=57). The adverse events were mostly related to anti-TNFs infusion. Conclusions: Combined surgical and anti-TNFs therapy did not significant improve the fistula closure than the surgery or anti-TNFs therapy alone. However, it is superior to either therapy in preventing fistula recurrence of fistulising perianal CD without causing more adverse events.

P221 Natural history of perianal Crohn's disease in patients with elderly-onset disease: a population-based study

P221 Natural history of perianal Crohn's disease in patients with elderly-onset disease: a population-based study

DOP058 Does biologic therapy increase the risk for fistula-associated mucinous adenocarcinoma in long standing perianal Crohn's disease?

DOP058 Does biologic therapy increase the risk for fistula-associated mucinous adenocarcinoma in long standing perianal Crohn's disease?

P153 Role of 3D endoanal ultrasound in perianal fistulising Crohns's disease. Preliminary results

Background: Perianal fistulising Crohn's Disease is a challenging clinical situation; the development of appropriate diagnostic tools is crucial for correct patient's management. The role of 3D endoanal ultrasound is well established in the diagnosis of anal fistulas. In this report we investigate if these some specific endosonogaphic features (the Crohn's Ultrasound Fistula Sign -CUFS, a double track, the presence of debris in the fistula track or abscess, the maximum width of the fistula tract) may have a role in discriminating between cryptoglandular and Crohn's Disease related fistulas. Methods: 48 consecutive patients with anal fistulas were included in the study from July 2015 to January 2016. Each patient underwent a 3D endoanal ultrasound (B-K Medical, 2052 transducer) and subsequent surgery. 11 patients had an established diagnosis of CD. The abovementioned ultrasonographic features were searched for and compared between the cryptoglandular fistulas group (“crypt group”) and the CD related fistulas group (“CD group”). Cohen K Statistics was used to determine the agreement between ultrasound diagnosis (primary orifice, tract) and operative findings. Wilcoxon rank sum test has been used to compare the fistula width between cryptogenic and CD cases. Diagnostic accuracy of the Width of the fistula tract has also been evaluated with a ROC curve and the AUC. The role of all the abovementioned signs and ultrasonography features as diagnostic tools for perianal fistulising CD has also been investigated and Sensitivity, Specificity, Accuracy, Positive and Negative Predictive Value (PPV/NPV) and Positive and Negative Likelihood ratios (PLR/ NLR) have been calculated. Statistical analysis were performed using STATA 12 statistical software. Results: Preoperative ultrasound and surgical findings showed a very good agreement (k=0.96 for primary orifice and k=0.94 for fistula tract). Mean width of the fistula tract was 2.7 mm in the crypt group and 5.1 mm in the CD group (p<0.001, Wilcoxon rank sum Test). A width over 4 mm has been proposed as a cut-off for highly suspicious CD related fistulas. The frequency observed of the CUFS, double track, debris and width >4 mm is significantly higher in the CD group than in the crypt group (p<0.01, Fisher exact test). All of these signs show a high sensitivity, specificity, positive and negative predictive value and a high positive likelihood ratio for diagnosis of perianal Crohn's disease. Conclusions: Endoanal 3D ultrasound is a safe and reliable tool for diagnosis of perianal fistulas; some specific ultrasonographic features have been described to discriminate between cryptoglandular and perianal CD related fistulas, with a high level of diagnostic accuracy.

P398 An objective measure of response to treatment for patients with Crohn's perianal fistulas on anti-TNF treatment

Background: Magnetic Resonance Imaging (MRI) is the preferred test for assessing fistulising perianal Crohn's disease and its response to anti-TNF therapy. Currently, radiological assessment of perianal fistulas and whether it has responded to treatment is subjective and variable according to radiologist interpretation. This study investigates a complementary objective measurements to reduce inter and intra-observer variability. Methods: A cohort of patients with perianal Crohn's fistulas treated at a tertiary centre with anti-TNF therapy was identified, and for whom pelvic MRI was available at baseline and follow-up. Two gastrointestinal radiologists measured fistula volumes, mean signal intensity and time taken to measure fistula volumes on baseline and follow-up MRI scans using a validated open-source segmentation software programme. One gastrointestinal radiologist repeated the measurements after 2 months. Three different gastrointestinal radiologists also assessed fistula response to treatment (improved/worse/unchanged) by comparing the MRI scans for each patient. Agreement between these radiologists was assessed using the kappa statistic. Intra-class correlation coefficient (ICC) was used to compare agreement between radiologists and to assess intra-observer variability for one radiologist. Results: Eighteen patients were recruited of which 6 (33%) were female and median age was 29 years old (range 19–52). Inter-observer variability was very good for volume and mean signal intensity with ICC of 0.95 (95% CI 0.91–0.98) and 0.95 (95% CI 0.90- 0.97) respectively. Intra-observer variability for one radiologist was also very good for volume and mean signal intensity with ICC of 0.99 (95% CI 0.97–0.99) and 0.98 (95% CI 0.95- 0.99) respectively. Average time taken to calculate volume measurements was 202 and 250 seconds for readers 1 and 2. Subjective assessment of response between the 3 radiologists was good; kappa of 0.69 (95% CI, 0.49–0.90). All 3 radiologists agreed in 72% of patients. A significant association was found between percentage volume change and subjective consensus agreement of response made by the radiologists (p=0.001). Median volume change for improved, stable or worsening fistula response was -67% (IQR −78, −47), 0% (IQR −16, +17), and +487% (IQR +217, +559) respectively. Conclusions: Objective measurements of fistula volume and signal intensity on MRI scans can be made rapidly using segmentation software with good agreement between radiologists. Percentage changes in measured volume are significantly correlated with judgements of response made by radiologists and could potentially be used to decrease variability in fistula assessment. These measurements can potentially be used to track fistula response over time.

P576 Could the hyperbaric oxygen therapy be an effective adjuvant therapy for fistulising Crohn's disease?

Background: Hyperbaric oxygen therapy (HBOT) is a treatment modality utilising 100% oxygen in a hyperbaric chamber, under increased pressure conditions. Blood hyperoxygenation provides better oxygen penetration into the tissues in accordance with the laws of physics [1], thereby reducing the inflammatory response by reducing the adhesion of leukocytes to the vascular endothelium of damaged tissues, reducing the production of Pro-Inflammatory Cytokines, stimulating angiogenesis, improving metabolism and antibacterial and antifungal action [2]. The aim of our observation is to prove that HBOT therapy may be an effective adjuvant therapy for fistulising Crohn's Disease (CD). Methods: Observations were made in 7 patients with active perianal fistulising CD. Three patients (the first group) were in the course of biological therapy and immunomodulatory therapy, while the other four (the second group) were administered only standard immunomodulatory therapy. Both groups have undergone HBOT according to the following protocol: 30 session, 90 minutes each, with pressure of 2.5 standard atmosphere. Analysis of clinical disease activity was performed by means of CDAI scale, biomarkers (fecal calprotectin (FC), blood CRP) and imaging studies: endoscopy and magnetic resonance imaging (MRI) of the pelvis with contrast. Observational study was divided into 4 stages: stage I – prior to treatment, stage II-HBOT therapy, stage III-after completing the HBOT treatment, stage IV – 6 weeks after HBOT. Regression of lesions confirmed in clinical evaluation and imaging studies was assigned as the end point. Results: Analysis of the group of patients showed clinical improvement in CDAI in 2 out of 3 patients from the first group and in 3 out of 4 from the second group. Levels of FC decreased in all 3 patients form the first group and in 3 out of 4 from the second group, while the level of blood CRP decreased in one patient from the first group and one patient from the second group. Imaging studies (MRI, endoscopy) showed regression of lesions in 2 out of 3 patients from the first group and in 3 out of 4 patients from the the second group. The summary of results is presented in Table 1. Table 1 Conclusions: On the basis of the results recorded in both groups of assessed patients we can conclude that HBOT may be an effective way to support the treatment of CD by improving clinical improvement and significantly reducing the occurrence of inflammatory lesions in the imaging studies. This is a preliminary report, as the study is ongoing.

Mesenchymal stem/stromal cell therapy for inflammatory bowel disease: an updated review with maintenance of remission.

There is a need for novel therapies for inflammatory bowel diseases (IBDs) that are well tolerated and effective. Currently, mesenchymal stem/stromal cells (MSCs) are being investigated in clinical trials for treatment of IBD. In this review, we update the recently published studies with an emphasis on the long-term efficacy of MSC therapy for IBD. A cumulative body of data, including a recent phase III randomized controlled trial demonstrated excellent fistula healing in patients with refractory Crohn's perianal fistulae treated via local injections of MSCs and with a good safety profile. Follow-up studies suggest long-term efficacy of MSC therapy for complex perianal Crohn's disease fistulae; however, the efficacy decreases over time and may necessitate repeat treatment. Systemic (intravenous) therapy for luminal IBD offers a relatively well tolerated alternative but its efficacy remains unclear. Recent studies demonstrate that MSCs are well tolerated and have an excellent short-term efficacy for the management of refractory fistulizing perianal Crohn's disease. The current data suggest that its influence may 'wear off' over time. More data on larger number of patients with longer duration of follow-up in the setting of a randomized placebo controlled trial are needed to confirm these promising results. For luminal IBD, there is a need for more mechanistic studies in representative preclinical murine models, and the results of an ongoing phase III randomized controlled trial are eagerly awaited.

IV．Crohn病における肛門病変に対する外科的治療の最前線

Crohn病における肛門病変の術後長期経過を中心に自験例の検討を行った．10年以上観察中の298例中82.9％に肛門病変をみとめ，115例（38.6％）が肛門病変先行例であった．外科治療の対象となる瘻孔・膿瘍は難治性のため，通常の痔瘻とは異なる対応を必要とする．手術施行例の検討では，瘻孔切除術（lay open法）は高率の再発に肛門括約筋のダメージが加わり，単発瘻孔といえども長期経過は不良であった．Seton法については，複数回のドレナージによる寛解例まで加えると67.1％で感染病巣が制御できており，活動性直腸病変，膣瘻などが不良因子となっていた．人工肛門により88.9％は肛門症状が軽減したが，閉鎖した3例とも肛門病変は再燃した．Crohn病肛門病変に対する外科的治療は，若年者が対象となるだけに長期的な肛門機能の保持まで考慮した症状の軽減とQOLの改善を目標とした術式の選択が重要である．

Asians Have More Perianal Crohn Disease and Ocular Manifestations Compared with White Americans

Background: Inflammatory bowel disease (IBD) is increasing in Asians. We sought to better understand differences in IBD between Asians and whites in the United States (US). Methods: We used data from the Sinai-Helmsley Alliance for Research Excellence cohort to assess disease characteristics for US-born Asians, Asian immigrants, and whites. We used bivariate analyses to describe clinical characteristics by race. We used logistic regression to determine baseline odds of immunosuppression and binomial regression to estimate risk ratios for worsening disease at follow-up. Results: We included 5,223 whites, 35 US-born Asians, and 81 Asian immigrants. Crohn disease (CD) was present in 64% of whites, 40% of US-born Asians, and 51% of Asian immigrants. At baseline, 58% of whites, 62% of US-born Asians, and 67% of Asian immigrants were in remission by disease activity index score (p = 0.238). There were no significant differences in CD location and behavior or ulcerative colitis extent. Asians had significantly more perianal disease than whites (33 vs. 18%, p = 0.007). Asians were more likely to have ocular manifestations than whites (3.4 vs. 0.7%, p = 0.022). Asians were also significantly less likely to be depressed than whites (25 vs. 35%, p = 0.022). Adjusting for confounders, Asians had half the odds of being treated with biologics compared with whites (OR: 0.45, 95% CI: 0.30-0.67). Adjusting for disease behavior and remission status, there were no differences in IBD-related surgery or hospitalization, new biologic or steroid prescription, or relapse rates between Asians and whites at follow-up. Conclusion: Asians are more likely to have perianal disease and ocular extraintestinal manifestations. After controlling for confounders, Asians were less likely to be treated with biologic agents. Despite this, there were no significant differences in outcomes over time between Asians and whites. Differences in disease phenotypes in Asians may reflect differences in genetics.

Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease.

AIMTo evaluate the imaging course of Crohn’s disease (CD) patients with perianal fistulas on long-term maintenance anti-tumor necrosis factor (TNF)-α therapy and identify predictors of deep remission.METHODSAll patients with perianal CD treated with anti-TNF-α therapy at our tertiary care center were evaluated by magnetic resonance imaging (MRI) and clinical assessment. Two MR examinations were performed: at initiation of anti-TNF-α treatment and then at least 2 years after. Clinical assessment (remission, response and non-response) was based on Present’s criteria. Rectoscopic patterns, MRI Van Assche score, and MRI fistula activity signs (T2 signal and contrast enhancement) were collected for the two MR examinations. Fistula healing was defined as the absence of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined as the association of both clinical remission, absence of anal canal ulcers and healing on MRI. Characteristics and imaging patterns of patients with and without deep remission were compared by univariate and multivariate analyses.RESULTSForty-nine consecutive patients (31 females and 18 males) were included. They ranged in age from 14-70 years (mean, 33 years). MRI and clinical assessment were performed after a mean period of exposure to anti-TNF-α therapy of 40 ± 3.7 mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%, and 26.5% of patients, respectively. Deep remission was observed in 32.7% of patients. Among the 26 patients in clinical remission, 10 had persisting inflammation of fistulas on MRI (T2 hyperintensity, n = 7; contrast enhancement, n = 10). Univariate analysis showed that deep remission was associated with the absence of rectal involvement and the absence of switch of anti-TNF-α treatment or surgery requirement. Multivariate analysis demonstrated that only the absence of rectal involvement (OR = 4.6; 95%CI: 1.03-20.5) was associated with deep remission.CONCLUSIONDeep remission is achieved in approximately one third of patients on maintenance anti-TNF-α therapy. Absence of rectal involvement is predictive of deep remission.

Surgery in Pediatric Crohn's Disease: Indications, Timing and Post-Operative Management.

Pediatric onset Crohn's disease (CD) tends to have complicated behavior (stricture or penetration) than elderly onset CD at diagnosis. Considering the longer duration of the disease in pediatric patients, the accumulative chance of surgical treatment is higher than in adult onset CD patients. Possible operative indications include perianal CD, intestinal stricture or obstruction, abdominal abscess or fistula, intestinal hemorrhage, neoplastic changes and medically untreatable inflammation. Growth retardation is an operative indication only for pediatric patients. Surgery can affect a patient's clinical course, especially for pediatric CD patient who are growing physically and mentally, so the decision should be made by careful consideration of several factors. The complex and diverse clinical conditions hinder development of a systemized treatment algorithm. Therefore, timing of surgery in pediatric CD patients should be determined with individualized approach by an experienced and well organized multidisciplinary inflammatory bowel disease team. Best long-term outcomes will require proactive post-operative monitoring and therapeutic modifications according to the conditions.

Analysis of clinical characteristics of perianal Crohn's disease in a single-center

To discuss the clinical features of perianal Crohn disease (PCD). Clinical data of 52 PCD patients who were treated at the Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine from June 2011 to October 2014 were analyzed retrospectively. Montreal classification, clinical symptoms, the subtype of perianal lesions, history of perianal surgery and medical treatment, disease active indexes, serum inflammation markers and nutritional indexes were included. Among 52 patients, there were 40 males and 12 females with a mean age of (27.9±9.1) years. According to Montreal classification, 51.9%(27/52) of patients had ileocolic involvement and 75.0%(39/52) had inflammatory disease behavior. Thirteen (25.0%) and 15(28.8%) patients had abdominal pain and diarrhea respectively at admission. With respect to the subtype of perianal lesions, there were 32(61.5%) cases of anal fistula and 16(30.8%) cases of perianal abscess. Thirty-nine(75.0%) and 33(63.5%) patients had a history of perianal surgery and medical treatment before admission resepectively. Laboratory findings revealed high C-reaction protein level in 63.5%(33/52), high erythrocyte sedimentation rate in 61.5%(32/52), elevated platelet in 32.7%(17/52), low body weight in 44.2%(23/52), low albumin in 26.9%(14/52) and anemia in 42.3%(22/52) of patients. The clinical features of PCD patients include male predominant, early onset disease, high prevalence of ileocolic involvement and inflammation disease behavior. Features prompting underlying PCD diagnosis include characteristic gastrointestinal symptoms, requiring multiple perianal surgery, and abnormality of inflammation markers and nutritional indexes.

Tumor Necrosis Factor Alpha Inhibitors Did Not Influence Postoperative Morbidity After Elective Surgical Resections in Crohn's Disease.

The real impact of anti-tumor necrosis alpha (TNF) therapy in postoperative complications after intestinal resections in Crohn's disease (CD) still needs to be determined. To compare the postoperative complication rates after elective intestinal resections in CD patients, with or without previous exposure to anti-TNF therapy. This was a retrospective and observational study, with elective intestinal resections for CD (emergency procedures were excluded). Patients were allocated in two groups according to preoperative anti-TNF status. Surgical and medical complications were analyzed and subsequently compared between the groups. A total of 123 patients were included (71 with and 52 without preoperative anti-TNF). The groups were considered homogeneous, except for perianal CD, previous azathioprine, and stomas. There was no significant difference between the groups regarding overall surgical complications (32.69% in anti-TNF- vs. 39.44% in anti-TNF+patients, p=0.457) or overall medical complications (21.15 vs. 21.13%, respectively, p=1.000). In univariate analysis, previous steroids, perianal CD, and stomas were considered risk factors for surgical complications, and previous steroids and hypoalbuminemia for medical complications. In multivariate analysis, previous steroids were associated with higher rates of surgical and medical complications, while hypoalbuminemia was associated with higher medical complication rates. There was no influence of the previous use of anti-TNF agents in postoperative surgical and medical complication rates in elective intestinal resections for CD. Previous steroids and hypoalbuminemia were associated with higher complication rates. This was the first case series of the literature describing outcomes in exclusively elective operations.

Fistula-Associated Anorectal Cancer in the Setting of Crohn's Disease.

Cancer arising from perianal fistulas in patients with Crohn's disease is rare. There are only a small series of articles that describe sporadic cases of perianal cancer in Crohn's disease fistulas. Therefore, there are no clear guidelines on how to appropriately screen patients at risk and choose proper management. The purpose of this study was to describe patients diagnosed with cancer in perianal fistulas in the setting of Crohn's disease. The study involved an institutional review board-approved retrospective review of medical charts of patients with perianal Crohn's disease. The data extracted from patient charts included demographic and clinical characteristics. Patients seen at the Mount Sinai Medical Center were included. We identified patients who were diagnosed with perianal cancer in biopsies of fistula tracts. We observed the number of patients with Crohn's disease who had fistulas, cancer in fistula tract, and time to diagnosis. The charts of 2382 patients with fistulizing perianal Crohn's disease were reviewed. Cancer in a fistula tract was diagnosed in 19 (0.79%) of these patients, 9 with squamous-cell carcinoma and 10 with adenocarcinoma. The majority of the 19 patients (68%) had symptoms typical of perianal fistula. The mean time from diagnosis of Crohn's disease to fistula diagnosis and from fistula diagnosis to cancer diagnosis was 19.4 and 6.0 years. In 5 patients (26%), cancer was not diagnosed in the first biopsy obtained from the fistula tract. This is a retrospective chart review of a rare outcome; the results may not be generalizable. Routine biopsies of long-standing fistula tracts in patients with Crohn's disease should be strongly considered and may yield an earlier diagnosis of cancer in the fistula tracts.

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population.

Inflammatory bowel diseases are chronic, relapsing, inflammatory conditions. They have a genetic backround resulting in patient susceptibility. The aim of our study is to investigate the involvement of IL23R, JAK2, and STAT3 polymorphisms in inflammatory bowel diseases in a Turkish population. Polymorphisms in IL23R (rs11209026), JAK2 (rs10758669), and STAT3 (rs3816769, rs2293152, rs744166, rs957970, rs8074524) were genotyped in 69 Crohn's disease patients, 157 ulcerative colitis patients, and 89 healthy controls. The presence of (C) in rs10758669, (T) and (TT) in rs957970, and (TT) in rs744166 were found to increase the susceptibility to Crohn's disease (p=0.049, p=0.016, p=0.010, p=0.035, respectively), while rs2293152 (GC), rs744166 (CT), and rs957970 (CT) provide protection against Crohn's disease (p=0.007, p=0.043, p=0.043, respectively). While rs2293152 (GC) was protective, rs2293152 (CC) increased the susceptibility to ulcerative colitis (p=0.009, p=0.001). All the polymorphisms were associated with age-at-diagnosis, except rs11209026. Furthermore, rs2293152 was associated with an extension in ulcerative colitis, while rs10758669, rs3816769, rs744166, rs2293152, and rs957970 were associated with the subphenotype in Crohn's disease. The presence of rs10758669 (AC) was protective against perianal Crohn's disease (p=0.016). Additionally, rs10758669 and rs2293152 in Crohn's disease and rs8074524, rs3816769, and rs10758669 in ulcerative colitis were associated with the requirement of immunsuppression. Finally, rs8074524 and rs10758669 in Crohn's disease and rs11209026 in ulcerative colitis were associated with disease-related operation. This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population. It was demonstrated that these polymorphisms may be effective in the etiology of inflammatory bowel disease in this Turkish population.