Indeterminate Colitis Patients Research Articles

SARCOPENIA AT INITIAL DIAGNOSIS OF PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Inflammatory bowel disease (IBD) can impact patients’ nutritional status. Poor oral intake, poor nutrient absorption, stool protein loss, and increased energy requirement all contribute. Poor nutritional status can manifest as inadequate growth, reduced weight gain, and sarcopenia, defined as decreased muscle mass and strength. Studies demonstrate decreased muscle mass in pediatric IBD patients leads to higher rates of therapy escalation, surgery, and post-operative complications. We sought to obtain the muscle mass at IBD diagnosis via cross-sectional imaging, compare to pediatric age- and sex-specific psoas muscle reference values for pediatric norms, and analyze muscle mass comparison between IBD subtypes and correlations with anthropometrics at diagnosis. METHODS Patients with new diagnosis of IBD [Crohn’s disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC)] aged 6-16 at diagnosis during 1/01/2016 through 12/31/2019 at our tertiary care facility were included in this retrospective study. Those with chronic medical conditions and lack of cross-sectional imaging within 3 months of diagnosis were excluded. Demographic and anthropometric data at diagnosis of IBD were obtained. The psoas muscle area in mm2 was measured on cross-sectional imaging at lumbar level 3-4 (L3-4) and 4-5 (L4-5) bilaterally to obtain total psoas muscle area (TPMA) at each level and compared to pediatric reference values. Statistical analysis included analysis of variance and Spearman correlations, performed using SAS v9.4. RESULTS Cross-sectional imaging from 162 patients with newly diagnosed IBD were reviewed. Average age was 12.1 years, with male predominance of 93 patients (57.4%). Most patients were diagnosed with CD (n=119, 73.5%), followed by UC (n=39, 24.1%), and IC (n=4, 2.5%) (Table 1). Measures of sarcopenia at both lumbar levels for TPMA and both lumbar levels z-score showed significant difference across IBD subtypes (Table 2). CONCLUSIONS Negative mean TPMA z-score < -1 was noted in all patients at both L3-4 and L4-5 levels, with a statistically significant difference between IBD types and mean TPMA at L3-4, TPMA at L4-5, mean z-score at L3-4, and mean z-score at L4-5. In a subgroup analysis, UC patients were significantly different from CD patients on all four measures, suggesting a higher rate of sarcopenia in CD patients at diagnosis. We plan to expand analysis to compare sarcopenia with disease location, medical therapy, hospitalization rate, need for surgical intervention, and anthropometrics over time. We hope to underscore importance of sarcopenia as measure of nutritional status at diagnosis, particularly when patients present with normal anthropometrics. Table 1 Table 2 SUBGROUP COMPARISONS Ulcerative Colitis patients were significantly different from Crohn’s Disease patients on all 4 measures. Indeterminate Colitis patients were significantly different from Ulcerative Colitis patient on the 2 Total Psoas Muscle Area Measures.

A nationwide study of patients hospitalized with indeterminate colitis: a comparison with Crohn's disease and ulcerative colitis.

Indeterminate colitis (IC) is subtype of colonic inflammatory bowel disease (IBD) that has features of both Crohn's disease (CD) and ulcerative colitis (UC). There have also been no studies to date examining patients hospitalized with IC in the United States (US). We examined the demographic and clinical characteristics of patients admitted with IC and compared them with patients admitted with CD and UC. We also analyzed trends in cost and length of stay (LOS). Patients admitted with IC tended to be female (58%), Caucasian (72%), and younger [39 (SD: 23) years]. Patients with IC underwent lower endoscopy at higher rates (26%; CD: p < 0.001, UC: p = 0.08) but bowel surgery at lower rates compared to those with CD (11% vs. 16%; p = 0.04). Patients with IC were found to have a higher rate of bowel obstruction (4% vs. 0.7%, p = 0.004) than those with UC, but lower rates of abscess and obstruction compared to patients with CD (p < 0.001). When the analysis was confined to patients who underwent bowel surgery, IC patients still demonstrated higher rates of lower endoscopy (p = 0.03) but lower rates of abscess compared to CD patients (p = 0.049). Costs increased significantly over time for CD- and UC-related hospitalizations, but not for admissions related to IC. This is the first nationwide US study illustrating the demographics and clinical characteristics of patients hospitalized with IC. We conclude that IC has notable differences in hospitalization characteristics compared to the main two IBD subtypes.

Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). Development of EIPD was not associated with number or type of preoperative advanced therapies.

Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn's Colitis among Indeterminate Colitis Cohorts.

Inadequate differentiated diagnostic features of predominantly colonic inflammatory bowel diseases i.e., ulcerative colitis and Crohn's colitis, may lead to inexact diagnosis of "indeterminate colitis". About 15% of indeterminate colitis patients are diagnosed at colonoscopy, in colonic biopsies, and/or at colectomy. Managing outcomes of indeterminate colitis, given its unpredictable clinical presentation, depends on future diagnosis of colitis, Crohn's colitis or ulcerative colitis. Overview the diagnostic efficacy of ectopic colonic ileal metaplasia and human α-defens 5 (DEFA5 alias HD5) for accurate delineation of indeterminate colitis into authentic Crohn's colitis and/ or ulcerative colitis. We describe a targeted protein for potentially differentiating indeterminate colitis into an accurate clinical subtype diagnosis of inflammatory bowel diseases i.e., ulcerative colitis and Crohn's colitis. Twenty-one patients with the clinically inexact diagnosis of indeterminate colitis were followed, reassessed and data analyzed. We observed that (i) some patients had their original diagnosis changed from indeterminate colitis to either ulcerative colitis or Crohn's colitis; and (ii) human α-defensin 5 is aberrantly overexpressed in Crohn's colitis. Fifteen of the twenty-one (71.4%) patients with indeterminate colitis had their inconclusive diagnosis changed; nine patients changed to ulcerative colitis and six to Crohn's colitis. In human colon surgical samples, Human α-defensin-5 was significantly upregulated in Crohn's colitis. In addition, Human α-defensin 5 processing enzyme, matrix metalloptotease-7 was inversely expressed compared to Human α- Defensin 5. Due to the sequence homology of the α-defensin class of proteins, preceding efforts to raise antibodies (Abs) against DEFA5 have limitations to produce adequate specificity. The Abs used in previous assays recognizes the α-defensins, active α-defensins 5 and inactive pro- α-defensins 5. Monoclonal antibodies (mAbs) to determine specificity and sensitivity of α-defensins 5, which is diagnostic of CC disease, and NOT other α-defensins is the limitation to overcome. It is feasible to differentiate ulcerative colitis from Crohn's colitis among patients with inexact diagnosis of indeterminate colitis using Human α-defensin 5 as a molecular biosignature delineator.

Indeterminate Colitis - Update on Treatment Options.

Indeterminate colitis (IC) is described in approximately 5–15% of patients with inflammatory bowel disease (IBD). It usually reflects a difficulty or lack of clarity in distinguishing between ulcerative colitis (UC) and Crohn’s disease (CD) on biopsy or colectomy specimens. The diagnostic difficulty may explain the variability in the reported prevalence and incidence of IC. Clinically, most IC patients tend to evolve over time to a definite diagnosis of either UC or CD. IC has also been interchangeably described as inflammatory bowel disease unclassified (IBDU). This review offers an overview of the available limited literature on the conventional medical and surgical treatments for IC. In contrast to the numerous studies on the medical management of UC and CD, there are very few data from dedicated controlled trials on the treatment of IC. The natural evolution of IC more closely mimics UC. Regarding medical options for treatment, most patients diagnosed with IC are treated similarly to UC, and treatment choices are based on disease severity. Others are managed similarly to CD if there are features suggestive of CD, including fissures, skin tags, or rectal sparing. In medically refractory IC, surgical treatment options are limited and include total proctocolectomy (TPC) and ileal pouch–anal anastomosis (IPAA), with its associated risk factors and complications. Post-surgical complications and pouch failure rates were historically thought to be more common in IC patients, but recent meta-analyses reveal similar rates between UC and IC patients. Future therapies in IBD are focused on known mechanisms in the disease pathways of UC and CD. Owing to the lack of IC-specific studies, clinicians have traditionally and historically extrapolated the data to IC patients based on their symptomatology, clinical course, and endoscopic findings.

P139 Significant Changes In Routine Biochemical Markers Occur Up To 5 Years Prior To Inflammatory Bowel Disease Diagnosis: A Case-Control Study

Abstract Background Early diagnosis of inflammatory bowel diseases (IBD) is associated with improved response to treatment and disease outcomes. Predicting patients at risk of developing symptomatic IBD would provide a window of opportunity to treat patients before irreversible bowel damage is caused. Our aim is to determine whether there is a pattern of change in use of health resources, medications and laboratory results in the years prior to diagnosis. Methods This is a retrospective study performed using electronic medical records (EMR) of Maccabi Health Services (MHS) which insures 25% of the Israeli population with a nationwide distribution. Data was extracted using MDClone (MDClone Ltd). IBD patients ≥ 16 years of age and minimum of 5 years follow up were identified by entry into the MHS IBD registry and included in the study. Demographic, clinical, medication and laboratory data was collected. Generalized estimating equation (GEE) model was applied to study trends and compare between years. Results A total of 5643 IBD patients were included. Of these, 3039 (53.8%) had Crohn’s disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). The mean age of the total IBD population at inclusion to the registry was 39.3 ± 16.5 years. Overall, CD patients had significantly increased visits to general practitioners, emergency rooms and admissions compared to UC patients (33.2 vs 30, p&amp;lt;0.0001; 0.2 vs 0.17, p&amp;lt;0.0001 and 0.88 vs 0.71, p&amp;lt;0.0001, respectively). CD and IC patients had similar patterns of medical professional/institution visits. Laboratory parameters such as haemoglobin and mean corpuscular volume showed significant decrease and white blood count, platelets and c-reactive protein showed significant increase in mean values primarily in the 2 years prior to diagnosis with stable values prior to that (p&amp;lt;0.0001 for all parameters). In contrast, parameters such as creatinine, total protein, albumin and calcium showed earlier significant and progressive decreases in mean values starting 5 years prior to diagnosis (p&amp;lt;0.0001 for all parameters) (Figure 1). Use of medications such as nonsteroidal anti-inflammatory drugs, etanercept, steroids, proton pump inhibitors and antibiotics significantly increased in the 2 years prior to IBD registry entry (P&amp;lt;0.0001 for all). Conclusion There are clear changes from baseline in uptake of medical resources, medication usage and laboratory results in the 5 years prior to IBD diagnosis. Parameters such as creatinine and albumin give earlier signal than others. This data may allow the development of an algorithm stratifying patients into those who need more intensive follow-up or investigations to enable earlier disease diagnosis.

Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.

Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 (DEFA5) expansion in the colonic mucosa of Crohn’s colitis disease (CC) patients. These areas of ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis of CC. Retrospectively, we: 1. Identified 21 patients with indeterminate colitis (IC) between 2000–2007 and were reevaluation their final clinical diagnosis in 2014 after a followed-up for mean 8.7±3.7 (range, 4–14) years. Their initial biopsies were analyzed by DEFA5 bioassay. 2. Differentiated ulcer-associated cell lineage (UACL) analysis by immunohistochemistry (IHC) of the CC patients, stained for Mucin 6 (MUC6) and DEFA5. 3. Treated human immortalized colonic epithelial cells (NCM460) and colonoids with pure DEFA5 on the secretion of signatures after 24hr. The control colonoids were not treated. 4. Treated colonoids with/without enterotoxins for 14 days and the spent medium were collected and determined by quantitative expression of DEFA5, CCLCs and other biologic signatures. The experiments were repeated twice. Three statistical methods were used: (i) Univariate analysis; (ii) LASSO; and (iii) Elastic net. DEFA5 bioassay discriminated CC and ulcerative colitis (UC) in a cohort of IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96 percent. IHC staining of CC for MUC6 and DEFA5 stained in different locations indicating that DEFA5 is not co-expressed in UACL and is therefore NOT the genesis of CC, rather a secretagogue for specific signature(s) that underlie the distinct crypt pathobiology of CC. Notably, we observed expansion of signatures after DEFA5 treatment on NCM460 and colonoids cells expressed at different times, intervals, and intensity. These factors are key stem cell niche regulators leading to DEFA5 secreting CCLCs differentiation ‘the colonic ectopy ileal metaplasia formation’ conspicuously of pathogenic importance in CC.

PATIENTS’ JOURNEY THROUGH INFLAMMATORY BOWEL DISEASE (IBD): A QUALITATIVE STUDY

Abstract Background Inflammatory bowel disease (IBD) is a debilitating intestinal condition, manifesting as Crohn’s disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC). The patient experience is impacted by a lack of awareness from other stakeholders despite growing global disease prevalence. To gain deeper insight of the patient experience, promote quality care, and enhance quality of life, we performed a qualitative study of the patient journey starting from pre-diagnosis through treatment. Methods U.S. patients with IBD were recruited via UC/CD support groups and organizations, social media platforms, blog followers, and personal networks. Participants were screened via an emailed survey and asked to self-identify as medically diagnosed on the basis of reported diagnostic testing. Interviews were conducted by qualitative researchers by phone or web conferencing. Open-ended questions were developed to support and gather information about our learning objectives—primarily, our desire to understand the unique experiences of UC/CD patients in their journey from symptom onset through diagnosis, treatment and maintenance (e.g. “Upon diagnosis, what were your immediate thoughts about the condition?”). This qualitative data were analyzed using Human-Centered Design methodology, including patient typologies (personas), forced temporal zoom (journey maps), forced semantic zoom (stakeholder system mapping), and affinity mapping for pattern recognition of unmet needs. Results A total of 32 patients were interviewed: N=17 CD patients, N=13 UC patients and N=2 IC patients. The interviewed population reflected regional, demographic, and disease-related diversity (Table 1). Five unique, mutually exclusive journeys were identified to understand and classify patient experiences: (1) Journey of Independence, (2) Journey of Acceptance, (3) Journey of Recognition, (4) Journey of Passion and (5) Journey of Determination (Figure 1). Patients with IBD expressed a need for increased awareness, education, and training for providers to shorten the path to diagnosis. Mental health support was found to be a critical gap in care, particularly for major treatment decisions (e.g., surgery). The inclusion of emotional support into the treatment paradigm was perceived as essential to long-term wellness. Patient attitudes and self-advocacy varied on their individual journeys; understanding these journeys may accelerate time to diagnosis and treatment. Conclusion Better understanding of patient journeys can help healthcare providers improve their approach to patient care and coordination.

Systematic review with meta-analysis: a history of smoking is not associated with a higher risk of pouchitis.

Ileal pouch-anal anastomosis is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis or indeterminate colitis. Tobacco smoking has been associated with protection from onset of ulcerative colitis. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. To examine the influence of smoking on the risk of pouchitis. We identified 15 studies evaluating smoking as a risk factor for developing pouchitis in ulcerative colitis or indeterminate colitis patients with a history of ileal pouch-anal anastomosis in a systematic search performed from inception through May 4, 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios (RR) and 95% confidence intervals (CI). A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR=0.94, 95% CI 0.76-1.18, I2 =73.7%). There was also no significant risk of pouchitis when comparing current smokers vs nonsmokers (RR=0.93, 95% CI 0.70-1.24, I2 =78.5%) and former smokers vs nonsmokers (RR=0.96, 95% CI 0.74-1.23, I2 =78.5%). Smoking, past or present, is not associated with an increased risk for the development of pouchitis in patients with ulcerative colitis or indeterminate colitis.

Inflammatory Bowel Disease in Children: Experience and Constraints in a Resource-limited Setting.

Introduction: Inflammatory bowel disease (IBD), though well described in the Caucasian population, is rarely encountered in the black African children. The aim of this study was to increase the awareness of this emerging condition in African children and highlight the constraints of management in a resource-limited setting like Nigeria.Methods: This study included an audit of children with IBD who were seen between January 2015 and February 2020 at the Lagos University Teaching Hospital (LUTH). The clinical records of children aged one to 16 years who presented with recurrent abdominal pain, weight loss, and gastrointestinal (GI) bleeding with clinical suspicion of IBD were reviewed. Clinical features, endoscopic findings, histopathologic findings, and treatment were documented.Results: Eight children with IBD were seen during the study period. The median age was 12.0 years (range: five to 15 years). The most common reported concerns in the children were chronic abdominal pain [seen in four patients (50%)] and bloody diarrhea [seen in three patients (42.30%)]. Weight loss and arthritis were seen in three (37.5%) and one (12.5%) children, respectively. Endoscopy confirmed two cases of Crohn’s disease (CD), three cases of ulcerative colitis (UC), and three cases of indeterminate colitis (IC). The children with CD were treated with steroids and exclusive enteral nutrition, with one patient receiving methotrexate, while the UC and IC patients received 5-aminosalicylate therapy.Conclusion: Although IBD is uncommon in Nigeria, a high index of suspicion is vital to enable early diagnosis and appropriate treatment. Management in the African setting is severely constrained by limited access to endoscopy facilities and nonavailability of other effective treatment options such as biologic agents.

Is Mean Platelet Volume a Useful Noninvasive Biomarker for Inflammatory Bowel Disease in Childhood?

ABSTRACT Introduction The incidence of inflammatory bowel disease (IBD) has become a global disease in newly industrialized countries. Inflammation leads to a structural modification in platelets, and the secretion of cytokines results in a change of mean platelet volume (MPV). Aim To evaluate the relationship between IBD activity parameters and MPV. Materials and methods The study group included 26 patients [consisting of 18 ulcerative colitis (UC), 6 Crohn's disease (CD), and 2 indeterminate colitis patients] followed-up at Dr. Behçet Uz Children's Hospital between 2004 and 2016. The data of patients were screened retrospectively and the demographic, clinical and laboratory characteristics were evaluated. The changes in MPV during the activation, remission and relapse periods of the disease and correlation with other disease activity markers were investigated. Results The study group consisted of 26 IBD patients (female/male: 11/15) and 71 healthy controls. We used the Pediatric Ulcerative Colitis Activity Index and the Pediatric Crohn's Disease Activity Index to determine disease activity. The IBD group had statistically significantly higher leukocyte count and lower hemoglobin values compared with the control group (p = 0.05). The mean platelet count and MPV values were not correlated significantly with both the C-reactive protein level and erythrocyte sedimentation rate (p &gt; 0.05). Conclusion We suggest that MPV is a simple and inexpensive method that can be useful in the diagnosis of IBD but does not provide significant results to determine the disease activity. How to cite this article Çinleti T, Bağ Ö, Ecevit ÇÖ. Is Mean Platelet Volume a Useful Noninvasive Biomarker for Inflammatory Bowel Disease in Childhood? J Med Sci 2020;6(1):4–7.

Impact of anti-TNF-alpha therapy on colectomy rate and indications for colectomy in ulcerative colitis: comparison of two patient cohorts from 2005 to 2007 and from 2014 to 2016

Objectives: The aim of this study is to assess the impact of biological therapy on the colectomy rate and indications for colectomy in ulcerative colitis (UC) at Helsinki University Hospital (HUH) catchment area in Finland.Methods: This study was conducted retrospectively by comparing two cohorts of UC and indeterminate colitis patients that underwent colectomy in a single centre in HUH during the years 2005–2007 and 2014–2016. All patient data were collected from hospital patient records.Results: In 2005–2007 and 2014–2016, respectively, 2.3 and 18.8% of patients had received biological therapy and more specifically 2.3 and 10.5% infliximab within 3 months prior to colectomy. Colectomy rates were 8.6 (7.2–10.2) and 5.1 (4.3–6.1)/1.000 patient-years (p < .001). During 2005–2007 and 2014–2016, the indications for colectomy were: refractory disease 79.1 and 79.7%, dysplasia 16.3 and 12.8%, cancer 2.3 and 3.0% and other reasons 2.3 and 4.5%, respectively. Emergency colectomy covered 8.5 and 9.8% of the operations.Conclusions: In addition to the markedly increased use of biological therapy during the time preceding colectomy, we noticed a significantly decreased rate of surgery but no changes in the indications for colectomy. Biological therapy seems to have had a favourable effect on the colectomy rate. Even so, the main indication for surgery is still a refractory disease, suggesting urgent need for better treatment options.

Long-term outcomes following ileal pouch-anal anastomosis in patients with indeterminate colitis

BackgroundThe advisability of performing ileal pouch–anal anastomosis for patients with indeterminate colitis is debated. Indeterminate colitis is found in up to 15% of inflammatory bowel disease colectomy specimens. We determined long-term outcomes in patients diagnosed with indeterminate colitis undergoing ileal pouch–anal anastomosis. MethodsFifty-six patients were included with a mean follow-up of 14 ± 7 years. Long-term behavior was defined based on surgeon assessment as “Crohn disease–like” in patients who subsequently developed clear signs of Crohn disease and as “non-Crohn disease–like.” Long-term function was assessed using the Cleveland Global Quality of Life and Pouch Functional Score. ResultsThirty-nine percent of patients developed Crohn disease–like behavior, and 61% developed non-Crohn disease–like behavior. Both groups experienced a high rate of pouchitis (57%). Crohn disease–like patients required more anti-inflammatory/immunomodulatory medications (95% vs 18%, P < .001), dilatations for afferent-limb strictures (41% vs 0%, P < .001), and pouch reoperations (32% vs 6%, P = .02). Eight patients required pouch excision or diversion (7 with Crohn disease–like behavior). The Pouch Functional Score was equivalent between groups. ConclusionLong-term function after ileal pouch–anal anastomosis for the majority of indeterminate colitis patients was good. Approximately 40% eventually exhibited Crohn disease–like behavior, but the majority had acceptable function and quality of life. Ileal pouch–anal anastomosis is an appropriate surgical option for indeterminate colitis patients after informed consent.

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.

Long-Term Outcomes in Indeterminate Colitis Patients Undergoing Ileal Pouch-Anal Anastomosis: Function, Quality of Life, and Complications

IntroductionIt is uncertain whether the outcomes of patients with indeterminate colitis (IC) undergoing ileal pouch-anal anastomosis (IPAA) deteriorate over time. The aim of this study was to determine the long-term pouch function, quality of life, complications, and incidence of Crohn’s disease after IPAA for patients with IC compared to ulcerative colitis (UC). MethodsA case matched analysis was performed on patients undergoing IPAA for pathologically confirmed IC or UC, between 1985 and 2014. Patients were case matched for age ± 5 years, gender, date of surgery ± 3 years, type of anastomosis and presence of a diverting loop ileostomy. All patients were followed up for greater than six months. Results448 patients were case matched, the average age was 36.8 year old and 52.7 % of patients were male. Mean follow-up was 122.06 months (+/− 80.77 months). There were statistically and clinically comparable number of daytime bowel movements (5.7 v 5.5, p = 0.45), rates of incontinence (26.1 % v 18.3 %, p = 0.09) and nighttime seepage in patients (23.1 % v 28.4 %, p = 0.28) with IC and UC. Quality of life markers and patient restrictions were comparable between the two groups. Rates of pelvic sepsis (IC 8.5 %, UC 8.5 %, p = 0.99) and anastomotic leak (IC 3.1 %, UC 4.0 %, p = 0.61) were similar but fistula formation (IC 15.6 %, UC 8.0 %, p = 0.01) and IPAA Crohn’s disease rates (IC 6.7 %, UC 2.7 %, p = 0.04) were significantly increased in IC patients. There was no statistically significant difference in pouch failure rates for IC and UC (5.8 % vs.4.9 %, p = 0.58). ConclusionPatients undergoing IPAA for IC have a higher risk of post-operative fistulae and development of Crohn’s disease, but comparable morbidity, functional outcomes, quality of life scores and pouch failure rates when compared to UC patients. Long-term data confirms that IPAA is a good surgical option in patients with IC.

585 Long-Term Outcomes in Indeterminate Colitis Patients Undergoing Ileal Pouch-Anal Anastomosis: Function, Quality of Life and Complications

585 Long-Term Outcomes in Indeterminate Colitis Patients Undergoing Ileal Pouch-Anal Anastomosis: Function, Quality of Life and Complications

Characteristics of Inflammatory Bowel Disease Serology in Patients With Indeterminate Colitis

Inflammatory bowel disease (IBD) serology testing is often used in patients with indeterminate colitis (IC) to help distinguish between ulcerative colitis (UC) and Crohn's disease (CD). We investigated the performance of serology testing in predicting future diagnosis in this setting. This was an observational study of individuals with IC at a single center who underwent IBD serology testing [anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), and anti-outer membrane porin C antibody (anti-OmpC)] and had at least 12 months follow-up from the time of serology test results. A total of 117 individuals with IC and with 1-year follow-up data were enrolled. All IC patients had endoscopic and histologic evidence of colitis at enrollment. One year after serology testing, 58 (50%) individuals with IC were diagnosed with UC, 49 (42%) with CD, and 10 (9%) remained labeled with IC. The sensitivity/specificity of an initial positive pANCA for a subsequent diagnosis of UC was 78%/44%. For ASCA and anti-OmpC, the results were 18%/84% and 27%/75%, respectively, for a subsequent diagnosis of CD. A positive pANCA test was associated with a likelihood ratio (LR) of 1.4 [95% confidence interval (CI), 1.1-1.8] for a subsequent diagnosis of UC at 1 year. Neither positive ASCA (LR 1.1; 95% CI, 0.5-2.5) nor anti-OmpC (LR 1.1; 95% CI, 0.6-2.0) was associated with a subsequent diagnosis of CD in patients with IC. The disease phenotype in the majority of individuals initially labeled with IC evolved to be more consistent with either UC or CD on follow-up. pANCA, ASCA, and anti-OmpC, individually, were of limited utility in predicting a patient's subsequent disease phenotype.

Risk and Location of Cancer in Patients With Preoperative Colitis-Associated Dysplasia Undergoing Proctocolectomy

To evaluate the influence of preoperative dysplasia grade, appearance, and site on risk and location of cancer in patients with colitis. The ability to predict the presence and location of cancer in colitis patients with dysplasia is essential to facilitate recommendations regarding the necessity and type of surgery. Ulcerative and indeterminate colitis patients who underwent proctocolectomy for dysplasia were retrospectively selected. Patient characteristics and findings at colonoscopic surveillance were associated with findings on the surgical specimen by regression analysis. From 1984 to 2007, 348 proctocolectomy specimens with preoperative dysplasia showed cancer in 51 (15%) and dysplasia in 172 (49%) cases. Patients with preoperative high-grade dysplasia (HGD) had cancer in 29% compared with 3% in low-grade dysplasia (LGD) (P < 0.001). Patients with preoperative dysplasia-associated lesion/mass (DALM) had cancer in 25% compared with 8% in flat dysplasia (P < 0.001). In LGD with DALM, the risk of cancer was not significantly higher than in flat LGD (7% vs 2%, P = 0.3), but risk of cancer or HGD was higher with a threefold increase (29% vs 9%, P = 0.015). On multivariate analysis, HGD, DALM, and disease duration were independent risk factors for postoperative cancer. In patients with isolated colonic dysplasia above the sigmoid level, postoperative rectal involvement was limited. Risk of cancer for patients with HGD or DALM is substantial. Despite low risk of cancer in patients with flat LGD, threshold for surgery should be low given the high prevalence of postoperative pathologic findings. Only in selected cases, colonoscopic surveillance after discussion of associated risks may be acceptable, provided high patient compliance can be assured. Surgery should be considered in all other cases, because it is the only modality that can eliminate the risk of cancer. The location of preoperative dysplasia may allow for the clarification of the need for proctectomy especially in the poor risk surgical patient.

P520 Demographic features and long-term follow up outcome comparisons between patients with solo inflammatory bowel disease vs. inflammatory bowel disease and concomitant ankylosing spondylitis

Background: Aim of the study was to compare demographic features and the long term patient outcomes between inflammatory bowel disease (IBD) patients with and without ankylosing spondylitis (AS). Methods: An IBD clinic is run by our team since 1999 currently with 705 CD, 935 UC patients under the same registry. These patients’ files retrospectively were evaluated and 76 patients with IBD+AS [49 with Crohn’s disease (CD), 27 with ulcerative colitis (UC)] were identified and then each IBD+AS patient randomly was matched with the next two adjacent solo IBD patient with the same diagnosis so having 152 IBD (98 CD, 54 UC) patients as the control group. Besides comparing demographic features, the primary endpoint was to compare the rate of intestinal resections between both groups. Age at IBD and/or AS onset, age (if there is any) at resection, the mean follow up time, number of flares needing steroids, medications including the type, dosage and duration, presence of family history, sex, disease location, and behavior, presence of perianal fistulae, smoking status were noted. Patients with indeterminate colitis or AS patients developing intestinal inflammation under NSAID or biologic treatment were excluded. Results: AS significantly was more common in patients with CD (6.9%) than in patients with UC (2.8%) (p = 0.0001). Among 76 patients with IBD+AS, 52 (68%) first presented with IBD, 11 (15%) with AS, and the remaining 13 (17%) had both diagnoses at the same time. The mean age, age at diagnosis or at resection did not disclose any significant difference between both groups. Neither location nor behavior of IBD nor rate of perianal fistulae were different. The mean follow up time was significantly longer in patients with IBD+AS (44.49 vs 28.6mo; p = 0.0011), and the use of biologics, steroids significantly were more common among patients with IBD+AS (37% vs. 9% for biologics, p = 0.000; 43% vs. 28% for steroids, p = 0.026). 33 out of 152 (22%) IBD and 11 out of 76 (14%) IBD+AS patients underwent an intestinal resection (total colectomy for UC, resection for CD) during our follow up (p =NS). The Spearman correlation test identified significant relations between IBD duration, frequency of flares needing steroids and resection, but an age-sex adjusted regression analysis disclosed IBD duration as the only independent predictor for resection (R2 = 0.178; p = 0.016). Conclusions: The present study shows that up to 5% of IBD patients may have AS although it is twice more common in CD compared to UC patients. Patients with IBD+AS do not have a worse disease outcome than solo IBD patients. When both groups are analyzed together the only independent predictor for resection is the duration of IBD. P521 Cytomegalovirus infection and response to influenza vaccination in inflammatory bowel disease patients on anti-TNF therapy L. Guidi1 *, G. Andrisani1, D. Frasca2, P. Cattani3, M. Marzo1, C. Felice1, D. Pugliese1, A. Papa1, G.L. Rapaccini1, B.B. Blomberg2, A. Armuzzi1. 1Catholic University, IBD Unit, Complesso Integrato Columbus, Rome, Italy, 2Miller School of Medicine, Department of Microbiology and Immunology, Miami, United States, 3Catholic University, Clinical Laboratory Unit, Complesso integrato Columbus, Rome, Italy

Tuberculin skin testing in inflammatory bowel disease patients from an endemic area of Brazil

ObjectiveInflammatory bowel disease (IBD) is a chronic disorder involving the gastrointestinal tract. Immunosuppressive drugs are usually prescribed to treat IBD patients, and this treatment can lead to tuberculosis reactivation. This paper aimed to analyze tuberculin skin test (TST) results in IBD patients at a reference center in Brazil. MethodsWe evaluated TST results in IBD patients using a cross-sectional study. We also analyzed the medical records of patients treated at a reference IBD outpatient unit where TST is routinely performed. ResultsWe reviewed 119 medical records of 57 (47.9%) Crohn's disease (CD), 57 (47.9%) ulcerative colitis (UC) and 5 (4.2%) indeterminate colitis (IC) patients. The mean (SD) age was 43.5 (13.7) years old. TST was positive in 24 (20.2%) of the patients. TST was positive in 16/57 (28.1%) UC and 6/57 (10.5%) CD patients (prevalence ratio [PR] 2.7). Forty-one patients (34.5%) were taking immunosuppressive drugs (azathioprine or prednisone) at the time of the TST, and six of these patients (14.6%) had positive test results. Two patients using infliximab had negative TST results. Thirty-five of the 41 patients (85.4%) on immunosuppressive treatment were anergic compared with 73.1% (57/78) of the untreated patients (PR 1.2). ConclusionsPatients with IBD have TST results similar to the general Brazilian population. Within the IBD population, CD patients have a lower frequency of TST positivity than UC patients.