Perianal Fistula After Ileoanal Pouch in Patients With Ulcerative Colitis: A Review of 475 Patients Operated on at a Major IBD Center.

BACKGROUND: Ileoanal pouch anastomosis is the surgical treatment of choice for patients with intractable ulcerative colitis. Perianal disease is a feature that is often present in Crohn's disease and infrequently in ulcerative colitis. OBJECTIVE: The aim of this study is to identify the incidence and factors associated with the development of postoperative perianal fistula in patients undergoing ileoanal pouch anastomosis for ulcerative colitis. DESIGN: A prospectively collected database at the time of surgery with subsequent follow-up was utilized. SETTING: The study was conducted at a high-volume single institution. PATIENTS: We studied a series of 475 consecutive patients with preoperative diagnosis of ulcerative colitis who underwent ileoanal pouch anastomosis. MAIN OUTCOME MEASURES: The incidence of postoperative perianal fistula and the factors correlating with its development were primary outcome measures of the study. RESULTS: The overall number of patients developing perianal fistulas was 44 of 475 (9%). Eleven patients with perianal fistula (25%) required return to ileostomy, of which 7 had pouch excision. Patients who developed a postoperative perianal fistula had a younger age at the onset of disease, had a lower age at index surgery, and were more likely to be subsequently classified as indeterminate colitis or Crohn's disease. Patients developing perianal fistulas were also more likely to develop partial dehiscence or stricture of the ileoanal anastomosis. LIMITATIONS: This study spans nearly 40 years during which the surgical procedure evolved. CONCLUSIONS: Young age at the onset of disease, lower age at surgery, and postoperative diagnosis of Crohn's disease and indeterminate colitis were the factors correlating with perianal fistulas. Delayed healing of the ileoanal anastomosis with partial separation and/or stricture also correlated with the onset of perianal fistulas. The severity of rectal inflammation at the time of surgery or the presence of stapled versus handsewn anastomosis did not correlate with the development of perianal fistulas. See Video Abstract at http://links.lww.com/DCR/B705. FSTULA PERIANAL POSTERIOR A RESERVORIO ILEOANAL EN PACIENTES CON COLITIS ULCERATIVA UNA REVISIN DE PACIENTES OPERADOS EN UN CENTRO PRINCIPAL DE EII: ANTECEDENTES:El reservorio ileoanal es el tratamiento quirúrgico de elección para los pacientes con colitis ulcerativa intratable. La enfermedad perianal es una característica que a menudo está presente en la enfermedad de Crohn y con poca frecuencia en la colitis ulcerativa.OBJETIVO:El objetivo del estudio es identificar la incidencia y los factores asociados con el desarrollo de fístula perianal posoperatoria en pacientes sometidos a reservorio ileoanal por colitis ulcerativa.DISEÑO:Base de datos recopilada prospectivamente en el momento de la cirugía con seguimiento subsecuente.ENTORNO CLÍNICO:El estudio se llevó a cabo en una única institución de gran volumen.PACIENTES:Estudiamos una serie de 475 pacientes consecutivos con diagnóstico preoperatorio de colitis ulcerativa a los que se les realizó reservorio ileoanal.PRINCIPALES MEDIDAS DE VALORACIÓN:La incidencia de fístula perianal posoperatoria y los factores que se correlacionan con su desarrollo fueron las principales medidas de resultado del estudio.RESULTADOS:El número total de pacientes que desarrollaron fístulas perianales fue 44 de 475 (9%). Once pacientes con fístula perianal (25%) requirieron volver a la ileostomía, de los cuales 7 tuvieron resección del reservorio. Los pacientes que desarrollaron fístula perianal posoperatoria tenían edad más temprana al inicio de la enfermedad, menor edad en el momento de la cirugía inicial y tenían más probabilidades de ser clasificados posteriormente como colitis indeterminada o enfermedad de Crohn. Los pacientes que desarrollaron fístulas perianales también fueron más propensos a desarrollar dehiscencia parcial o estenosis de la anastomosis ileoanal.LIMITACIONES:Este estudio abarca casi 40 años durante los cuales ha evolucionado el procedimiento quirúrgico.CONCLUSIONES:Edad temprana al inicio de la enfermedad, menor edad al momento de la cirugía, diagnóstico postoperatorio de enfermedad de Crohn y colitis indeterminada fueron los factores que se correlacionaron con las fístulas perianales. El retraso en la cicatrización de la anastomosis ileoanal con separación parcial y/o estenosis también se correlacionó con la aparición de fístulas perianales. La gravedad de la inflamación rectal en el momento de la cirugía o la presencia de anastomosis con grapas versus anastomosis manual no se correlacionó con el desarrollo de fístulas perianales. Consulte Video Resumen en http://links.lww.com/DCR/B705.

From Paris to Montreal: disease regression is common during long term follow-up of paediatric Crohn's disease.

Introduction: Paediatric Crohn's disease (PCD) often presents with extensive and a frequent pan-enteric phenotype at onset. However, its long term evolution into adulthood, especially since the widespread use of biological agents, is not well characterised. We conducted a single centre cohort study of all PCD patients transitioned to adult care to assess the long term disease evolution in the era of biologic therapy.Methods: We conducted a retrospective observational, study of all PCD patients who were subsequently transferred to the care of an adult gastroenterology unit and had a minimum follow up of 2 years. We examined the case notes for evolution of disease location and behaviour. Disease location and behaviour was characterised using Paris classification at diagnosis and Montreal classification at last follow-up. In addition, we examined variables associated with complicated disease behaviour and the need for CD related intestinal resection.Results: In total, 132 patients were included with a median age at diagnosis of 13 (IQR 11-14) and a median follow up of 11 years (range 4-14). At diagnosis, 23 (17.4%), 39 (29.6%) and 70 (53%) patients had ileal, colonic and ileocolonic disease respectively. In addition, 31 (23.5%) patients had L4a or L4b disease at diagnosis (proximal or distal to the ligament of treitz respectively) and 13 patients (9.8%) had both whilst 27 (20.4%) patients had perianal disease. At diagnosis, 27 (20.4%) patients had complicated disease behaviour but 83 (62.9)% of patients had an extensive 'pan-enteric' phenotype. Of these patients only 55 (66.3%) retained the pan-enteric phenotype at last follow-up (p = .0002). Disease extension was noted in 25 (18.9%) of patients and regression was noted in 47 (35.6%) of patients, whereas upper GI disease was noted in significantly fewer patients at last follow-up (21, 15.9%) (p = .0001). More patients had complicated disease behaviour (46 patients, 34.9%, p = .0018) at last follow-up. There was a high exposure to both thiopurines 121 (91.7%) and biologics 84 (63.6%). The cumulative probability (95% CI) of surgery was 0.05 (0.02, 0.11) at 1 year, 0.17 (0.11, 0.24) at 3 years and 0.22 (0.15, 0.30) at 5 years. Neither disease location nor behaviour were associated with the need for intestinal resectional surgery.Conclusions: Over the course of an extended follow-up period, there appeared to be changes in both disease location and behaviour in PCD. Interestingly, a significant proportion of patients had disease involution which may be related to a high rate of exposure to thiopurines and biologics. We were unable to identify any variables associated with complicated disease course or the need for intestinal surgery.

Lower Risk of B1-to-pB3-Stage Migration in Crohn's Disease Upon Immunosuppressive and Anti-TNF Treatment in the Swiss IBD Cohort Study.

BACKGROUND: While the long-term evolution of disease behavior in Crohn's disease has been well described in the pre-anti-TNF era, our knowledge thereon remains scarce after the introduction of anti-TNF. AIMS: Our investigation examined the long-term evolution of disease concerning Montreal classification's B-stages over time in patients enrolled into the Swiss IBD Cohort Study between 2006 and 2017. METHODS: We analyzed prospectively collected SIBDCS data using a Markov model and multivariate testing for effects of treatment and other confounders on B-stage migration over time. The primary outcome was a transition in disease behavior from B1 to either B2 or pB3, or from B2 to pB3, respectively. RESULTS: The 10- and 15-year probability of remaining in B1 was 0.61 and 0.48, as opposed to a probability to migrate to B2 or B3 of 0.25 or 0.14, and 0.32 or 0.2, after 10 and 15 years, respectively. In multivariate testing, the hazard ratio for migrating from B1 to pB3 (HR 0.27) and from B2 to pB3 (HR 0.12) was lower in patients > 40 years compared to patients < 17 years. We found that immunosuppression (HR 0.38) and treatment with anti-TNF for > 1 year (HR 0.30) were associated with a decreased likelihood of transitioning from stage B1 to pB3. CONCLUSIONS: While in the anti-TNF era most patients with Crohn's disease will eventually develop stricturing and/or penetrating complications, our data indicate that immunosuppressive and anti-TNF treatment for more than 1 year reduce the risk of transitioning from stage B1 to pB3 in the long-term run.

Association Between Plasma Level of Collagen Type III Alpha 1 Chain and Development of Strictures in Pediatric Patients With Crohn's Disease.

BACKGROUND & AIMS: There are few serum biomarkers to identify patients with Crohn's disease (CD) who are at risk for stricture development. The extracellular matrix components, collagen type III alpha 1 chain (COL3A1) and cartilage oligomeric matrix protein (COMP), could contribute to intestinal fibrosis. We investigated whether children with inflammatory CD (B1) who later develop strictures (B2) have increased plasma levels of COL3A1 or COMP at diagnosis, compared with children who remain B1. We compared results with previously studied biomarkers, including autoantibodies against colony-stimulating factor 2 (CSF2). METHODS: We selected 161 subjects (mean age, 12.2 y; 62% male) from the Risk Stratification and Identification of Immunogenic and Microbial Markers of Rapid Disease Progression in Children with Crohn's cohort, completed at 28 sites in the United States and Canada from 2008 through 2012. The children underwent colonoscopy and upper endoscopy at diagnosis and were followed up every 6 months for 36 months; plasma samples were collected at baseline. Based on CD phenotype, children were separated to group 1 (B1 phenotype at diagnosis and follow-up evaluation), group 2 (B2 phenotype at diagnosis), or group 3 (B1 phenotype at diagnosis who developed strictures during follow-up evaluation). Plasma samples were collected from patients and 40 children without inflammatory bowel disease (controls) at baseline and analyzed by enzyme-linked immunosorbent assay to measure COL3A1 and COMP. These results were compared with those from a previous biomarker study. The Kruskal-Wallis test and the pairwise Dunn test with Bonferroni correction were used to compare differences among groups. RESULTS: The median baseline concentration of COL3A1 was significantly higher in plasma from group 3 vs group 1 (P < .01) and controls (P = .01). Median baseline plasma concentrations of COMP did not differ significantly among groups. A model comprising baseline concentrations of COL3A1 and anti-CSF2 identified patients with B2 vs B1 CD with an area under the curve of 0.80 (95% CI, 0.71-0.89); the combined concentration identified patients with strictures with a sensitivity value of 0.70 (95% CI, 0.55-0.83) and a specificity value of 0.83 (95% CI, 0.67-0.93). CONCLUSIONS: We found median plasma concentrations of COL3A1, measured by enzyme-linked immunosorbent assay at diagnosis, to be significantly higher in patients with CD who later developed strictures than in patients without strictures. The combination of concentrations of COL3A1 and anti-CSF2 might be used to identify pediatric patients at CD diagnosis who are at risk for future strictures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00790543.

Should We Divide Crohn's Disease Into Ileum-Dominant and Isolated Colonic Diseases?

Crohn's disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal tract. First described in 1932 as terminal ileitis or regional enteritis, it predominately involves the ileum with or without colonic involvement. Isolated colonic CD was first described in 1960 and since then the phenotypic classification of CD has evolved to stratify patients into isolated ileal, ileocolonic, or isolated colonic involvement. In the current review we evaluate the published literature regarding differences in epidemiology, natural history, pathogenesis, response to therapy, and disease monitoring, when stratified by disease location. Based on the available evidence consideration could be given to a new classification for CD, which splits it into ileum dominant (isolated ileal and ileocolonic) and isolated colonic disease. This may allow for a more optimized approach to clinical care and scientific research for CD.

Crohn Disease: A 5-Point MR Enterocolonography Classification Using Enteroscopic Findings.

OBJECTIVE: The objectives of our study were to establish the efficacy of a 5-point MR enterocolonography classification for assessing Crohn disease (CD) activity, compare this classification with a validated MRI score (i.e., the MR index of activity [MaRIA]), and compare both with endoscopic findings, which were assessed using the Crohn disease endoscopic index of severity (CDEIS). MATERIALS AND METHODS: Seventy (derivation cohort) and 50 (validation cohort) patients with CD were retrospectively enrolled in this study. We developed a 5-point MR enterocolonography classification that consists of visual assessments alone. MR enterocolonography results were evaluated for each bowel segment (rectum; sigmoid, descending, transverse, and ascending colon; terminal and proximal ileum; and jejunum) by one observer in the derivation phase and independently by three observers in the validation phase using the 5-point MR enterocolonography classification lexicon and MaRIA. Areas under the ROC curves (AUCs) in discriminating endoscopic deep ulcers were compared between the MR enterocolonography classification and MaRIA. Interobserver reproducibility was assessed using weighted kappa coefficients. RESULTS: The AUCs of the MR enterocolonography classification were 89.0% in the derivation phase and 88.5%, 81.0%, and 77.3% for the three observers in the validation phase. The AUCs of the MR enterocolonography classification were statistically noninferior to those of MaRIA (p < 0.001). The cross-validation accuracy was 81.9% in the derivation phase and 81.5% in the validation phase. The MR enterocolonography classification showed good reproducibility. CONCLUSION: The 5-point MR enterocolonography classification was shown to be effective for evaluating CD activity in the large and small bowel.

Molecular classification of Crohn's disease reveals two clinically relevant subtypes.

OBJECTIVE: The clinical presentation and course of Crohn's disease (CD) is highly variable. We sought to better understand the cellular and molecular mechanisms that guide this heterogeneity, and characterise the cellular processes associated with disease phenotypes. DESIGN: We examined both gene expression and gene regulation (chromatin accessibility) in non-inflamed colon tissue from a cohort of adult patients with CD and control patients. To support the generality of our findings, we analysed previously published expression data from a large cohort of treatment-naïve paediatric CD and control ileum. RESULTS: We found that adult patients with CD clearly segregated into two classes based on colon tissue gene expression-one that largely resembled the normal colon and one where certain genes showed expression patterns normally specific to the ileum. These classes were supported by changes in gene regulatory profiles observed at the level of chromatin accessibility, reflective of a fundamental shift in underlying molecular phenotypes. Furthermore, gene expression from the ilea of a treatment-naïve cohort of paediatric patients with CD could be similarly subdivided into colon-like and ileum-like classes. Finally, expression patterns within these CD subclasses highlight large-scale differences in the immune response and aspects of cellular metabolism, and were associated with multiple clinical phenotypes describing disease behaviour, including rectal disease and need for colectomy. CONCLUSIONS: Our results strongly suggest that these molecular signatures define two clinically relevant forms of CD irrespective of tissue sampling location, patient age or treatment status.

Does a histologically inflamed resection margin increase postoperative complications in patients with Crohn's disease?

OBJECTIVES: Our study assessed whether the presence of histologically inflamed resection margins increased postoperative anastomotic complications in Crohn's disease (CD) patients. We also examined the influence of other risk factors for postoperative complications. MATERIALS AND METHODS: Presence of chronic inflammation and activity of inflammation was scored from the resection margin specimens of 70 patients undergoing surgery due to CD. Anastomotic complications were recorded with a one-month follow-up. We also analysed other risk factors for postoperative complications, such as patient age, previous surgeries, preoperative C-reactive protein, faecal calprotectin, albumin and haemoglobin levels, American Society of Anesthesiologists (ASA) classification, preoperative immunosuppressive medication, surgical approach and the presence of intraoperative fistula or abscess. RESULTS: In total, 46 patients (65.7%) had active inflammation in the bowel resection margin - 12 patients (17.1%) with mild, five patients (7.1%) with moderate and 29 patients (41.4%) with strong activity. We found 14 (20.0%) postoperative complications, of which three (4.6%) were anastomotic. The presence of active inflammation at the resection margin did not significantly influence the occurrence of postoperative anastomotic complications. None of the other risk factors examined significantly increased postoperative complications among our sample. CONCLUSIONS: After bowel-sparing surgery for CD, the frequency of histologically inflamed resection margins is high. However, postoperative complication rate remains low. The current practice with resection of only the most affected bowel segments for CD seems to be a safe choice. We still need further research concerning risk factors for postoperative complications in Crohn's patients.

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Characteristics and Incidence Trends for Pediatric Inflammatory Bowel Disease in Daegu-Kyungpook Province in Korea: a Multi-Center Study.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous chronic disease of unknown etiology. Although it is an important disease that shows a rapid increase in pediatric population, there are no pediatric studies that represent a specific region in Korea. Therefore, we studied the epidemiological and phenotypic characteristics of pediatric IBD in Daegu-Kyungpook province, Korea. METHODS: We included 122 children with pediatric IBD initially diagnosed at one of four university hospitals in Daegu-Kyungpook province between July 2010 and June 2016. We investigated the incidence trends, and the clinical characteristics at diagnosis were compared by Paris classification. RESULTS: We included 122 children: 98 with Crohn's disease (CD) and 24 with ulcerative colitis (UC). The average age at diagnosis was 13.6 years for IBD. The incidence shows an increasing trend. CD showed a significant increase, whereas UC appears to be increasing slowly. In CD, there was a significant male predominance. For disease activity sites, the most common location was L3 (77.6%), indicating ileocolonic involvement as the major type. B1 (88.8%) was the most common disease behaviors type. Perianal disease was noted in 43 patients (43.9%) and weight loss in 60 (61.2%). In UC, E4 (58.4%) was the most common disease activity site, indicating pancolonic involvement as the major type. CONCLUSION: We found that the number of pediatric patients with IBD is increasing rapidly in Daegu-Kyungpook province in Korea. Our study also revealed that the characteristics of pediatric IBD in our province differ somewhat from those of pediatric IBD in Western countries.

Validation of the "German Inflammatory Bowel Disease Activity Index (GIBDI)": An Instrument for Patient-Based Disease Activity Assessment in Crohn's Disease and Ulcerative Colitis.

INTRODUCTION: Assessment of disease activity in Crohn's disease (CD) and ulcerative colitis (UC) is usually based on the physician's evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians' documented activity indices. METHODS: Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. RESULTS: Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). DISCUSSION: There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

Crohn's disease: is there any link between anal and luminal phenotypes?

PURPOSE: Perianal Crohn's disease (CD) encompasses a variety of lesion similar to luminal disease, which are usually not distinctly assessed. Links between luminal and perianal CD phenotype remains therefore underreported, and we aimed to describe both luminal and perianal phenotype and their relationships. METHODS: From January 2007, clinical data of all consecutive patients with CD seen in a referral center were prospectively recorded. Data recorded until October 2011 were extracted and reviewed for study proposal. RESULTS: A total of 282 patients (M/F, 108/174; aged 37.8 ± 16.2 years) were assessed that included 154 cases (54.6%) with anal ulceration, 118 cases (41.8%) with fistula, 49 cases (17.4%) with stricture, and 94 cases without anal lesion (33.3%). Anal ulcerations were associated with fistulas (N = 87/154) in more than half of patients (56.5%) and were isolated in 55 patients (35.7%). Most of strictures (94%) were associated with other lesions (N = 46/49). Harvey-Bradshaw score was significantly higher in patients with ulcerations (p < 0.001) as compared to those with perianal fistulas (p = 0.15) or with anal strictures (p = 0.16). Proportions of complicated behavior (fistulizing or stricturing) of luminal CD were similar according to anal lesions: anal fistulas were not significantly associated to penetrating Montreal phenotype (N = 4/31 p = 0.13) as well as anal stricture and stricturing Montreal phenotype (N = 3/49, p = 0.53). CONCLUSIONS: The phenotype of luminal disease does not link with the occurrence and the phenotype of perianal Crohn's disease. Anal ulcerations denote a more severe disease on both luminal and perianal locations and should consequently be taking into account in physician decision-making.

Addition of Histology to the Paris Classification of Pediatric Crohn Disease Alters Classification of Disease Location.

OBJECTIVES: The aim of the study was to investigate the value of microscopic findings in the classification of pediatric Crohn disease (CD) by determining whether classification of disease changes significantly with inclusion of histologic findings. METHODS: Sixty patients were randomly selected from a cohort of patients studied at the Pediatric Inflammatory Bowel Disease Clinic at the University of California, San Francisco Benioff Children's Hospital. Two physicians independently reviewed the electronic health records of the included patients to determine the Paris classification for each patient by adhering to present guidelines and then by including microscopic findings. RESULTS: Macroscopic and combined disease location classifications were discordant in 34 (56.6%), with no statistically significant differences between groups. Interobserver agreement was higher in the combined classification (κ = 0.73, 95% confidence interval 0.65-0.82) as opposed to when classification was limited to macroscopic findings (κ = 0.53, 95% confidence interval 0.40-0.58). When evaluating the proximal upper gastrointestinal tract (Paris L4a), the interobserver agreement was better in macroscopic compared with the combined classification. CONCLUSIONS: Disease extent classifications differed significantly when comparing isolated macroscopic findings (Paris classification) with the combined scheme that included microscopy. Further studies are needed to determine which scheme provides more accurate representation of disease extent.

Radiologic Predictors of Surgery in Newly Diagnosed Pediatric Crohn Disease Patients.

OBJECTIVES: The aim of the present study was to assess whether small bowel imaging conducted at the time of diagnosis could be used as a predictor of small bowel surgical intervention in a population of pediatric patients with Crohn disease (CD). METHODS: A retrospective analysis of small bowel imaging within 30 days of diagnosis of pediatric CD was conducted. Patients were divided into 2 groups based on small bowel imaging: those with no or minor abnormalities (71%) and those with more extensive or obstructive abnormalities (29%). Medical records were reviewed for small bowel surgical intervention and clinic follow-up visits. RESULTS: A total of 232 patients were included in the study group (average age at diagnosis 11.7 years). Twenty-seven patients (12%) underwent small bowel surgical intervention. The relative risk for small bowel surgical intervention was 2.91 in the group with more extensive imaging abnormalities. The majority of increased surgical risk occurred in the first year after diagnosis, when the normal-minor group had a 2% surgical risk and the more abnormal group had a 17% surgical risk. Both groups had a 2% to 3% surgical risk per year after the first year. CONCLUSIONS: Small bowel imaging at the time of diagnosis in pediatric CD can help predict the risk of small bowel surgical intervention and should be recommended for all newly diagnosed patients. Nearly one third of our cohort underwent small bowel surgical intervention through 8 years of follow-up. Surgical complications of CD often occur in the small bowel, and counseling families about surgical risk is an integral part of pediatric CD management.

Development of an Inflammatory Bowel Disease Research Registry Derived from Observational Electronic Health Record Data for Comprehensive Clinical Phenotyping.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous collection of chronic inflammatory disorders of the digestive tract. Clinical, genetic, and pathological heterogeneity makes it increasingly difficult to translate efficacy studies into real-world practice. Our objective was to develop a comprehensive natural history registry derived from multi-year observational data to facilitate effectiveness and clinical phenotypic research in IBD. METHODS: A longitudinal, consented registry with prospectively collected data was developed at UPMC. All adult IBD patients receiving care at the tertiary care center of UPMC are eligible for enrollment. Detailed data in the electronic health record are accessible for registry research purposes. Data are exported directly from the electronic health record and temporally organized for research. RESULTS: To date, there are over 2565 patients participating in the IBD research registry. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, laboratory values, health-related questionnaires quantifying disease activity and quality of life, and analytical information on treatment, temporally organized for 6 years (2009-2015). The data have resulted in a detailed definition of clinical phenotypes suitable for association studies with parameters of disease outcomes and treatment response. We have established the infrastructure required to examine the effectiveness of treatment and disease course in the real-world setting of IBD. CONCLUSIONS: The IBD research registry offers a unique opportunity to investigate clinical research questions regarding the natural course of the disease, phenotype association studies, effectiveness of treatment, and quality of care research.

Changes of Crohn's disease phenotype over time.

Background - Crohn's disease is a clinically heterogeneous condition. Our aim was to identify the phenotype evolution of Crohn's disease over time according to the Montreal Classification and to precise predictive factors of the need for immunosuppressant treatment or surgery. Methods - We included Crohn's disease patients who were followed up for at least 5 years. We excluded patients who were lost to follow up before five. Patients were classified according to the Montreal classification for phenotype at diagnosis and five years later. The evolution of phenotype over time and the need for surgery, immunosuppressive or immunomodulatory drugs were evaluated. Results - One hundred twenty consecutive patients were recruited: 70 males and 50 females. At diagnosis, 68% of patients belong to A2 as determined by the Montreal classification. Disease was most often localized in the colon. The disease location in Crohn's disease remains relatively stable over time, with 93.4% of patients showing no change in disease location. Crohn's disease phenotype changed during follow up, with an increase in stricturing and penetrating phenotypes from 6% to 11% after 5 years. The only predictive factor of phenotype change was the small bowel involvement (OR=3.7 [1.2-7.6]). During follow-up, 82% of patients have presented a severe disease as attested by the use of immunosuppressive drugs or surgery. The factors associated with the disease severity were: small bowel involvement (L1), the stricturing (B2) and penetrating (B3) phenotypes and perineal lesions (OR=17.3 [8.4-19.7]; 12 [7.6-17.2]; 3[1.7-8.3] and 2.8 [2.2-5.1] respectively), without association with age, sex or smoking habits. Conclusion - Crohn's disease evolves over time: inflammatory diseases progress to more aggressive stricturing and penetrating phenotypes. The ileal location, the stricturing and penetrating forms and perineal lesions were predictive of surgery and immunosuppressant or immunomodulatory treatment.

Ustekinumab induction and maintenance therapy in refractory Crohn's disease.

BACKGROUND: In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. METHODS: We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS: The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P=0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P=0.03) and response (69.4% vs. 42.5%, P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.).

Subclassification of small bowel Crohn's disease using magnetic resonance enterography: a review using evidence-based medicine methodology.

Magnetic resonance enterography (MRE) has a growing role in imaging small bowel Crohn's disease (SBCD), both in diagnosis and assessment of treatment response. Certain SBCD phenotypes respond well to biologic therapy and others require surgery; MRE has an expanding role in triaging these patients. In this review, we evaluate the MRE signs that subclassify SBCD using evidence-based medicine (EBM) methodology and provide a structured approach to MRE interpretation.

A think tank of the Italian society of colorectal surgery (SICCR) on the surgical treatment of inflammatory bowel disease using the Delphi method: Crohn's disease.

The management of Crohn's disease (CD) requires extensive expertise. Many treatment options are available, and surgery still plays a crucial role. In recent years, many medical societies have provided surgeons and gastroenterologists dealing with CD with authoritative guidelines. However, a certain degree of variation can be observed in these papers, and application of guidelines in clinical practice should be improved. The Italian society of colorectal surgery (SICCR) promoted the project reported here, which consists of a think tank of Italian colorectal surgeons to address the surgical aspects of CD management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of CD. The management of CD is, by necessity, patient-tailored, and it is based on clinical data and surgeon's preference, but the committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Standardized recording of parameters related to the natural history of inflammatory bowel disease: from Montreal to Paris.

Similar to adults, there is heterogeneous phenotypic expression of inflammatory bowel disease (IBD) in children. Thus, a classification system for disease characteristics is obligatory if one seeks to understand and eventually change the natural history of IBD. Extrapolation of adult clinical trial results to children also depends upon comparable classifications of disease. Features that can differentiate IBD in children from adults include more extensive and severe disease at presentation, frequent corticosteroid dependency, change in location and behavior over time, and the implications of disease for growth and sexual maturation. In contrast to the Montreal classification where all patients <17 years were grouped together, the Paris classification recognizes the different expression of pediatric IBD between those patients aged <10 years and those 10-17 years of age. The recent identification of monogenic disorders in very young children (<2 years) with severe IBD-like disease has further clouded the issue of where appropriate pediatric age guidelines should be drawn, though it is clear these infantile-onset cases should not be grouped with older children. The Paris classification recognizes the importance of upper tract disease on natural history by dividing it into L4a and L4b (proximal and distal to the ligament of Treitz, respectively), while the Montreal system groups all upper-tract patients together. Complicated disease behavior in the Montreal system mandated a single category preventing the concomitant designation as stricturing and penetrating, whereas the Paris classification recognizes that both stricturing and penetrating behavior may occur at the same or different times. Growth delay is recognized only in the Paris classification as a serious manifestation of IBD in children affecting therapeutic decisions. As our understanding of the basic molecular mechanisms of disease pathogenesis in IBD changes over time, it is likely that the IBD classification will change as well. A single classification system that reflects both pediatric and adult disease is needed.