Accuracy of optical diagnosis with narrow band imaging in the surveillance of ulcerative colitis: a prospective study comparing Kudo, Kudo-IBD and NICE classifications.

PURPOSE: The diagnostic accuracy of Narrow Band Imaging (NBI) in the endoscopic surveillance of ulcerative colitis (UC) has been disappointing in most trials which used the Kudo classification. We aim to compare the performance of NBI in the lesion characterization of UC, when applied according to three different classifications (NICE, Kudo, Kudo-IBD). METHODS: In a prospective, real-life study, all visible lesions found during consecutive surveillance colonoscopies with NBI (Exera-II CV-180) for UC were classified as suspected or non-suspected for neoplasia according to the NICE, Kudo and Kudo-IBD criteria. The sensitivity (SE), specificity (SP), positive (+LR) and negative (-LR) likelihood ratios of the three classifications were calculated, using histology as the reference standard. RESULTS: 394 lesions (mean size 6 mm, range 2-40 mm) from 84 patients were analysed. Twenty-one neoplastic (5%), 49 hyperplastic (12%), and 324 inflammatory (82%) lesions were found. The diagnostic accuracy of the NICE, Kudo and Kudo-IBD classifications were, respectively: SE 76%-71%-86%; SP 55-69%-79% (p < 0.05 Kudo-IBD vs. both Kudo and NICE); +LR 1.69-2.34-4.15 (p < 0.05 Kudo-IBD vs. both Kudo and NICE); -LR 0.43-0.41-0.18. CONCLUSION: The diagnostic accuracy of NBI in the differentiation of neoplastic and non-neoplastic lesions in UC is low if used with conventional classifications of the general population, but it is significantly better with the modified Kudo classification specific for UC.

Severe Disease Activity Based on the Paris Classification Is Associated with the Development of Extraintestinal Manifestations in Korean Children and Adolescents with Ulcerative Colitis.

BACKGROUND: There are limited data regarding the extraintestinal manifestations (EIMs) associated with pediatric inflammatory bowel disease (IBD) in Korea. We aimed to investigate the clinical features and factors associated with the development of EIMs in Korean children and adolescents with IBD. METHODS: This multicenter, retrospective study was conducted from 2010 to 2017. Baseline clinicodemographic, laboratory findings, disease activity, disease phenotypes, and EIMs were investigated. RESULTS: A total of 172 patients were included. One-hundred thirty-seven (79.7%) had Crohn's disease (CD), and 35 (20.3%) had ulcerative colitis (UC). EIMs occurred in 42 patients (24.4%). EIMs developed in 34/137 diagnosed with CD (24.8%), and in 8/35 diagnosed with UC (22.9%), during a median follow-up duration of 3.2 (interquartile range, 1.9-5.4) years for CD and 3.0 (1.0-4.0) years for UC, respectively. Arthritis/arthralgia was most commonly observed (n = 15, 35.7%), followed by stomatitis/oral ulcer (n = 10, 23.8%), hepatitis (n = 5, 11.9%), nephritis (n = 4, 9.5%), pancreatitis (n = 2, 4.8%), erythema nodosum (n = 2, 4.8%), pyoderma gangrenosum (n = 1, 2.4%), primary sclerosing cholangitis (n = 1, 2.4%), uveitis (n = 1, 2.4%), and ankylosing spondylitis (n = 1, 2.4%). A significant difference in disease severity based on the Paris classification (P = 0.011) and ESR at diagnosis (P = 0.043) was observed between the EIM positive and negative group in patients with UC. According to logistic regression analyses, S1 disease severity based on the Paris classification was the only factor that was significantly associated with the development of EIMs (odds ratio, 16.57; 95% confidence interval, 2.18-287.39; P = 0.017). CONCLUSION: Severe disease activity based on the Paris classification in pediatric patients with UC was significantly associated with EIM development. As disease severity in the Paris classification is a dynamic parameter, treatment should be focused on disease control to minimize the occurrence of EIMs in Korean children and adolescents with UC.

Multi-factor mediated functional modules identify novel classification of ulcerative colitis and functional gene panel.

Ulcerative colitis is a chronic, idiopathic, and inflammatory disease of the rectal and colonic mucosa, the behavior of which is of heterogeneity in individuals. Here, we explored the multifactor-mediated functional modules associated with ulcerative colitis classification in the whole genome. Datasets downloaded from the GEO database were used to identify differentially expressed genes between ulcerative colitis patients and healthy individuals initially, followed by acquisition of the remaining ulcerative colitis -related genes from the OMIM and STRING databases. The results identified 914 ulcerative colitis-related genes, of which 60 were differentially expressed genes obtained from GEO datasets. Through weighted co-expression network analysis of ulcerative colitis-related genes, four modules were obtained, three of which were related to ulcerative colitis. Following interactions between microRNA, long noncoding RNA, transcription factors, and module hub genes were predicted and used to construct ulcerative colitis multifactor networks. Additionally, we performed consensus clustering of the ulcerative colitis samples. The results revealed that ulcerative colitis could be divided into four subtypes, with six hub genes identified as potential biomarkers for classification. These findings offer novel insights into ulcerative colitis and a basis for disease classification of ulcerative colitis.

Assessing Severity of Disease in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic disease that can present at various stages of disease activity and severity. Traditionally, severity scoring has focused on disease activity during a single moment with various tools, including patient-reported symptoms, as well as clinical, laboratory-based, endoscopic, histologic, and imaging variables. Optimal delivery of care depends on the accurate assessment of disease severity, which must take longitudinal variables into account. This article reviews the history of severity scoring in UC and provides a concise, clinically oriented approach to assessing disease severity.

Classification of Inflammatory Bowel Disease from Formalin-Fixed, Paraffin-Embedded Tissue Biopsies via Imaging Mass Spectrometry.

PURPOSE: Discrimination between ulcerative colitis (UC) and Crohn's disease (CD) by histologic features alone can be challenging and often leads to inaccurate initial diagnoses in inflammatory bowel disease (IBD) patients. This is mostly due to an overlap of clinical and histologic features. However, exact diagnosis is not only important for patient treatment but it also has a socioeconomic impact. It is therefore important to develop and improve diagnostic tools complementing traditional histomorphological approaches. EXPERIMENTAL DESIGN: In this retrospective proof-of-concept study, the utilization of MALDI imaging is explored in combination with multi-variate data analysis methods to classify formalin-fixed, paraffin-embedded (FFPE) colon biopsies from UC (87 biopsies, 14 patients), CD (71 biopsies, 14 patients), and normal colonic (21 biopsies, 14 patients) tissues. RESULTS: The proposed method results in an overall balanced accuracy of 85.7% on patient and of 80.4% on sample level, thus demonstrating that the assessment of IBD from FFPE tissue specimens via MALDI imaging is feasible. CONCLUSIONS AND CLINICAL RELEVANCE: The results emphasize the high potential of this method to distinguish IBD subtypes in FFPE tissue sections, which is a prerequisite for further investigations in retrospective multicenter studies, as well as for a future implementation into clinical routine.

IL-13 mRNA Tissue Content Identifies Two Subsets of Adult Ulcerative Colitis Patients With Different Clinical and Mucosa-Associated Microbiota Profiles.

BACKGROUND AND AIMS: A personalized approach to therapy hold great promise to improve disease outcomes. To this end, the identification of different subsets of patients according to the prevalent pathogenic process might guide the choice of therapeutic strategy. We hypothesize that ulcerative colitis [UC] patients might be stratified according to distinctive cytokine profiles and/or to a specific mucosa-associated microbiota. METHODS: In a cohort of clinically and endoscopic active UC patients and controls, we used quantitative PCR to analyse the mucosal cytokine mRNA content and 16S rRNA gene sequencing to assess the mucosa-associated microbiota composition. RESULTS: We demonstrate, by means of data-driven approach, the existence of a specific UC patient subgroup characterized by elevated IL-13 mRNA tissue content separate from patients with low IL-13 mRNA tissue content. The two subsets differ in clinical-pathological characteristics. High IL-13 mRNA patients are younger at diagnosis and have a higher prevalence of extensive colitis than low IL-13 mRNA patients. They also show more frequent use of steroid/immunosuppressant/anti-tumour necrosis factor α therapy during 1 year of follow-up. The two subgroups show differential enrichment of mucosa-associated microbiota genera with a prevalence of Prevotella in patients with high IL-13 mRNA tissue content and Sutterella and Acidaminococcus in patients with low IL-13 mRNA tissue content. CONCLUSION: Assessment of mucosal IL-13 mRNA might help in the identification of a patient subgroup that might benefit from a therapeutic approach modulating IL-13. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Identifying Patients With Inflammatory Bowel Diseases in an Administrative Health Claims Database: Do Algorithms Generate Similar Findings?

Application of selective algorithms to administrative health claims databases allows detection of specific patients and disease or treatment outcomes. This study identified and applied different algorithms to a single data set to compare the numbers of patients with different inflammatory bowel disease classifications identified by each algorithm. A literature review was performed to identify algorithms developed to define inflammatory bowel disease patients, including ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified in routinely collected administrative claims databases. Based on the study population, validation methods, and results, selected algorithms were applied to the Optum Clinformatics® Data Mart database from June 2000 to March 2017. The patient cohorts identified by each algorithm were compared. Three different algorithms were identified from literature review and selected for comparison (A, B, and C). Each identified different numbers of patients with any form of inflammatory bowel disease (323 833; 246 953, and 171 537 patients, respectively). The proportions of patients with ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified were 32.0% to 47.5%, 38.6% to 43.8%, and 8.7% to 26.6% of the total population with inflammatory bowel disease, respectively, depending on the algorithm applied. Only 5.1% of patients with inflammatory bowel disease unspecified were identified by all 3 algorithms. Algorithm C identified the smallest cohort for each disease category except inflammatory bowel disease unspecified. This study is the first to compare numbers of inflammatory bowel disease patients identified by different algorithms from a single database. The differences between results highlight the need for validation of algorithms to accurately identify inflammatory bowel disease patients.

Is ulcerative colitis a disease of a dysfunctional microbiota?

Using the gross pathology literature and the prior decoupling of Crohn's disease from inflammatory bowel disease, IDI's White Paper puts into question the current understanding of what ulcerative colitis is and how it can be therapeutically addressed. The pathology literature, when coupled with the ability of fecal enema therapy to achieve a remission rate significantly superior to those documented for biologics, puts focus on the dominant role of the gastrointestinal microbiota in both disease induction and its recovery. The concept of endogenous enterotoxogenesis is introduced.

Redefining the IBDs using genome-scale molecular phenotyping.

The IBDs, Crohn's disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract resulting from an aberrant immune response to enteric microbiota in genetically susceptible individuals. Disease presentation and progression within and across IBDs, especially Crohn's disease, are highly heterogeneous in location, severity of inflammation and other phenotypes. Current clinical classifications fail to accurately predict disease course and response to therapies. Genome-wide association studies have identified >240 loci that confer risk of IBD, but the clinical utility of these findings remains unclear, and mechanisms by which the genetic variants contribute to disease are largely unknown. In the past 5 years, the profiling of genome-wide gene expression, epigenomic features and gut microbiota composition in intestinal tissue and faecal samples has uncovered distinct molecular signatures that define IBD subtypes, including within Crohn's disease and ulcerative colitis. In this Review, we summarize studies in both adult and paediatric patients that have identified different IBD subtypes, which in some cases have been associated with distinct clinical phenotypes. We posit that genome-scale molecular phenotyping in large cohorts holds great promise not only to further our understanding of the diverse molecular causes of IBD but also for improving clinical trial design to develop more personalized disease management and treatment.

Extensive Disease Subtypes in Adult Patients with Ulcerative Colitis: Non-pancolitis Versus Pancolitis.

BACKGROUND AND AIM: Few studies have compared pancolitis and non-pancolitis E3 in adult patients with ulcerative colitis (UC). This study aimed to evaluate the natural disease courses and factors affecting outcomes between pancolitis and non-pancolitis E3. METHODS: We retrospectively analyzed 117 patients, including 93 with extensive colitis (E3) and 24 with UC confined to the rectum or left-sided colon and appendiceal orifice inflammation at the time of diagnosis, who were regularly followed up for at least 1 year. Patients with E3 were divided into two groups according to the degree of disease extension: pancolitis group (disease extent up to the cecum or proximal ascending colon) and non-pancolitis E3 group (disease extent above the splenic flexure but not up to the proximal ascending colon). Clinical findings at diagnosis; comorbidity; medications; Mayo score; cumulative rates of corticosteroid, immunomodulator, and anti-tumor necrosis factor (anti-TNF) alpha use; relapse; and admission were compared between the pancolitis and non-pancolitis E3 groups. RESULTS: The median follow-up duration of the 117 patients was 74 (range 15-158) months. Fifty-one patients (43.5%) had pancolitis. The Mayo score at initial diagnosis, cumulative relapse rate, and cumulative admission rate were significantly higher in the pancolitis group than in the non-pancolitis E3 group (P < 0.001, P = 0.023 and P = 0.007, respectively). However, there was no significant difference between the groups in the rates of cumulative immunomodulator and anti-TNF alpha use (P = 0.67 and P = 0.73, respectively). CONCLUSIONS: In patients with extensive UC (E3), pancolitis was associated with higher probabilities of cumulative relapse or admission, indicating poor prognosis.

The emerging role of histologic disease activity assessment in ulcerative colitis.

BACKGROUND AND AIMS: Assessment of disease activity is essential for developing and determining appropriate therapy in patients with ulcerative colitis (UC). Validated clinical and endoscopic scoring systems have been established to accurately define disease activity. Clinical and endoscopic treatment targets have also been proposed, with gastroenterologists encouraged to optimize medical therapy to achieve these targets. Recently, histology has been recognized as an important prognostic factor and potential treatment target in patients with UC. METHODS: This review summarizes the recent literature regarding histologic scoring indices in UC and offers practical guidance to gastroenterologists on how to interpret histologic data. RESULTS: Substantial evidence indicates that histology accurately predicts clinical relapse, hospitalization, corticosteroid use, and development of dysplasia. Furthermore, compared with endoscopy, findings suggest that histology may be more predictive of these outcomes. Because microscopic disease activity can persist in the absence of clinical or endoscopic disease activity, histology may be the ideal marker of inflammation. Standardized definitions of histologic response and remission and a biopsy procurement protocol are needed to guide clinical decision making. It is recommended that overall assessment of disease severity be determined according to the worst affected biopsy fragment. Crypt architectural distortion, basal plasmacytosis, and neutrophilic activity should be reported. A 5-category classification system based on disease chronicity/activity and basal plasmacytosis is proposed. It is not yet necessary to report on the degree of mucosal eosinophilia or use a validated scoring system, although the latter may aid in determining therapeutic response. CONCLUSIONS: Although rarely used to measure inflammation and guide therapy, histologic disease activity is predictive of important clinical outcomes in UC. Randomized controlled trials are needed to determine whether histology should function as a treatment target.

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.

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.

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.

Endocytoscopic classification can be predictive for relapse in ulcerative colitis.

The present study was conducted to explore the association of endocytoscopy (EC) classification with microscopic inflammatory features of ulcerative colitis (UC) and disease relapse.EC was performed for mild-to-moderate UC 32 cases from January 2010 to August 2016. EC appearance was stratified into 4 categories: EC-A, regular arrangement of round to oval pits; EC-B, irregular arrangement with/without enlarged spaces between regular pits; EC-C, deformed pits with distorted crypt lumen which are unordered in arrangement but not disrupted; and EC-D, disruptive or disappeared pits. We evaluated the association of EC classification with Mayo endoscopic subscores (MES) and the clinically active state. Microscopic features including the severity in mucosal inflammatory infiltrates the presence of crypt abscess and goblet cell depletion were assessed by an experienced pathologist who was blinded to clinical and endoscopic information. Clinical follow-up was provided for treating 22 UC patients more than 60 months after EC.There were 15 cases in EC-A, 8 in EC-B, 5 in EC-C, and 4 in EC-D. Interobserver agreement was excellent with κ value of 0.77. There were 13 patients in active disease stage, while 19 in remission. Each EC-A case was in clinically remission stage, while all the EC-C and EC-D cases were in the active stage. There were 4 and 4 EC-B cases in remission and active stage, respectively. The EC-A group consisted of 11 MES0 and 4 MES1 cases, whereas the EC-B group consisted of 2 MES0 and 6 MES1 cases. There were no cases of MES0 in the EC-C and -D groups. The EC stratification was significantly associated with pathognomonic microscopic features for UC. There were significant differences in the remission rate among the EC groups. None had relapse in the EC-A group during the follow-up period.EC stratification could be predictive for relapse in UC. Moreover, EC is reliable to assess UC specific microscopic features.

The Long-Term Predictive Properties of the Paris Classification in Paediatric Inflammatory Bowel Disease Patients.

INTRODUCTION: The Paris modification of the Montreal classification for children with inflammatory bowel disease was accepted in 2011. We aimed to investigate the long-term clinical outcomes of patients diagnosed with IBD during childhood in a population-based cohort according to the Paris classification at diagnosis. METHODS: The medical records of paediatric inflammatory bowel disease patients, diagnosed from 2000 to 2016, were reviewed retrospectively. Main outcome measures included time to first flare, hospitalisation, surgery, and biologic therapy. RESULTS: In Crohn's disease patients [n = 301, median age 14.2 years], colonic location was associated with higher prevalence of extraintestinal manifestations, whereas ileal location and complicated behaviour were associated with anti-Saccharomyces cerevisiae antibody positivity. During a median follow-up of 9.1 years (interquartile range [IQR]of 4.7-12.3), complicated behaviour at diagnosis was associated with increased risk for surgery (hazard ratio[ HR] = 2.7, p < 0.001] and hospitalisation [HR = 1.5, p = 0.01] but not with the risk for flare or stepping-up to biologic therapy. Isolated colonic disease was associated with a decreased risk of surgery [HR = 0.25, p = 0.02]. During a median follow-up of 8.5 years [interquartile range of 5.1-12], in patients with ulcerative colitis [n = 126, median age 13.7 years], severe disease at diagnosis but not disease extent was associated with the risk for colectomy [HR = 3.5, p = 0.002], hospitalisation [HR = 3.3, p < 0.001], flare [HR = 2.4, p < 0.001] and biologic therapy [HR = 2.6, p = 0.001]. CONCLUSIONS: The Paris classification for paediatric inflammatory bowel disease has clear predictive properties. Complicated disease and ileal location at diagnosis in Crohn's disease, and severity of disease but not its extension in ulcerative colitis, predict long-term worse outcomes.

Pit pattern analysis with high-definition chromoendoscopy and narrow-band imaging for optical diagnosis of dysplasia in patients with ulcerative colitis.

BACKGROUND AND AIMS: Patients with longstanding ulcerative colitis (UC) are at increased risk of developing colorectal neoplasia. Chromoendoscopy (CE) increases detection of lesions, and Kudo pit pattern classification I and II have been suggested to be predictive of benign polyps in UC. Little is known on the use of this classification in nonmagnified high-definition (HD) (virtual) CE and narrow-band Imaging (NBI) or on the interobserver agreement. The aim of this pilot study was to assess the diagnostic accuracy and the interobserver agreement of the Kudo pit pattern classification in UC patients undergoing surveillance with methylene blue CE or NBI in a multicenter study. METHODS: Fifty images of lesions identified in 27 UC patients (13 neoplastic) either with classical CE (methylene blue .1%; n = 24) or NBI (n = 26) were selected by an independent investigator. Images were selected from a randomized controlled trial to compare CE and NBI. All nonmagnified images were obtained with a processor and mounted in a PowerPoint file in a standardized way (same size; black background). Ten endoscopists with extensive experience in NBI/CE were asked to assess the lesions for the predominant Kudo pit pattern (I, II, IIIL, IIIS, IV, and V) to indicate if they believed the lesion was neoplastic and how confident they were about the diagnosis. Histology was used as the criterion standard. RESULTS: Median sensitivity, specificity, negative predictive value, and positive predictive value for diagnosing neoplasia based on the presence of pit pattern other than I or II was 77%, 68%, 88%, and 46%, respectively. Diagnostic accuracy was significantly higher when a diagnosis was made with a high level of confidence (77% vs 21%, P < .001). The overall interobserver agreement for any pit pattern was only fair (κ = .282), with CE being significantly better than NBI (.322 vs .224, P < .001). From a clinical viewpoint the difference between neoplastic and non-neoplastic lesions is important. The agreement for differentiation between non-neoplastic patterns (I, II) and neoplastic patterns (IIIL, IIIS, IV, or V) was moderate (κ = .587) and even significantly better for NBI in comparison with CE (κ = .653 vs .495, P < .001). CONCLUSIONS: Differentiation between non-neoplastic and neoplastic pit patterns in UC lesions shows a moderate to substantial agreement among expert endoscopists. The agreement for differentiating neoplastic from non-neoplastic lesions is significantly better for NBI in comparison with HD CE. The assessment of pit pattern I or II with nonmagnified HD CE or NBI has a high negative predictive value to rule out neoplasia. (Clinical trial registration number: NCT01882205.).

Development and Validation of Diagnostic Criteria for IBD Subtypes Including IBD-unclassified in Children: a Multicentre Study From the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND: The revised Porto criteria identify subtypes of paediatric inflammatory bowel diseases: ulcerative colitis [UC], atypical UC, inflammatory bowel disease unclassified [IBDU], and Crohn's disease [CD]. Others have proposed another subclassifiction of Crohn's colitis. In continuation of the Porto criteria, we aimed to derive and validate criteria, termed "PIBD-classes," for standardising the classification of the different IBD subtypes. METHODS: This was a multicentre retrospective longitudinal study from 23 centres affiliated with the Port -group of ESPGHAN. Both a hypothesis-driven judgmental approach and mathematical classification and regression tree [CART] modelling were used for creating a diagnostic algorithm. Since small bowel inflammation is easily recognised as CD, we focused here primarily on the phenotype of colitis. RESULTS: In all, 749 IBD children were enrolled: 236 [32%] Crohn's colitis, 272 [36%] UC and 241 [32%] IBDU [age 10.9 ± 3.6 years] with a median follow-up of 2.8 years (interquartile range [IQR] 1.7-4.3). A total of 23 features were clustered in three classes according to their prevalence in UC: six class-1 features [0% prevalence in UC], 12 class-2 features [< 5% prevalence], and five class-3 features [5-10% prevalence]. According to the algorithm, the disease should be classified as UC if no features exist in any of the classes. When at least one feature exists, different combinations classify the disease into atypical UC, IBDU or CD. The algorithm differentiated UC from CD and IBDU with 80% sensitivity (95% confidence interval [CI] 71-88%) and 84% specificity [77-89%], and CD from IBDU and UC with 78% sensitivity [67-87%] and 94% specificity [89-97%]. CONCLUSIONS: The validated PIBD-classes algorithm can adequately classify children with IBD into small bowel CD, colonic CD, IBDU, atypical UC, and UC.

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.

Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era.

BACKGROUND AND OBJECTIVE: Approximately one-third of children with ulcerative colitis will experience at least 1 attack of acute severe colitis (ASC) before 15 years of age. Severe disease can be defined in children when Pediatric Ulcerative Colitis Activity Index is >65 and/or ≥6 bloody stools per day, and/or 1 of the following: tachycardia, fever, anemia, and elevated erythrocyte sedimentation rate with or without systemic toxicity. Our aim was to provide practical suggestions on the management of ASC in children. The goal of medical therapy is to avoid colectomy while preventing complications of disease, side effects of medications, and mortality. METHODS: A systematic search was carried out through Medline via PubMed to identify all articles published in English to date, based on the following keywords "ulcerative colitis," "pediatric ulcerative colitis," "biological therapy," and "acute severe colitis." Multidisciplinary clinical evaluation is recommended to identify early nonresponders to conventional treatment with intravenous corticosteroids, and to start, if indicated, second-line therapy or "rescue therapy," such as calcineurin inhibitors (cyclosporine, tacrolimus) and anti-tumor necrosis factor molecules (infliximab). RESULTS: Pediatric Ulcerative Colitis Activity Index is a valid predictive tool that can guide clinicians in evaluating response to therapy. Surgery should be considered in the case of complications or rapid clinical deterioration during medical treatment. CONCLUSIONS: Several pitfalls may be present in the management of ASC, and a correct clinical and therapeutic approach is recommended to reduce surgical risk.