Extensive Colonic Involvement Research Articles

Integrated Management of complex Fistula-in-Ano in a Patient with Ulcerative Colitis Using Kshara Sutra: A Unique Case Study

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation of the colon and rectum often leading to debilitating symptoms and complications. Fistula-in- Ano is a rare complication of UC, which is an abnormal tract connecting the anal canal to the skin surrounding the anus, further complicating management and impairing patients' quality of life which poses significant challenges in management due to its chronic and recurrent nature. Kshara Sutra, an Ayurvedic parasurgical procedure involving the use of medicated thread, has shown promising results in the treatment of complex Fistula-in-Ano in a patient with ulcerative colitis. Aim: To evaluate the efficacy of Kshara Sutra in the management of complex Fistula-in-Ano in a patient with Ulcerative colitis. Material and Methods: A Hindu, married 56 yrs. old male patient came in Shalya Department of Naradevi Ayurveda Hospital, Kathmandu Nepal with a chief complaints of recurrent episodes of bloody diarrhea, abdominal pain, and perianal discharge over a span of four years. Diagnostic workup revealed extensive colonic involvement consistent with UC on colonoscopy and imaging confirmed the presence of a fistula-in-ano. The patient was diagnosed as a case of Fistula-in Ano with clinical findings & examination done. Then Kshara sutra Ligation was planned along with internal medications. Results/Discussions: After 6 months of treatment, result was achieved remarkably. Conclusion: This case highlights the potential efficacy and safety of Kshara Sutra therapy as an adjunctive and safest treatment modality for managing complex Fistula-in-Ano in patients with underlying ulcerative colitis.

Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA

The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales registry. Data extraction was conducted in July2021. A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17-40 y) (relative risk ratio, 1.45; 95% CI, 1.31-1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38-1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14-1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07-1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38-1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79-0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70-0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71-0.82), and complications (odds ratio, 0.73; 95% CI, 0.66-0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26-1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66-0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67-0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55-0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69-0.88). There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.

Clinical features of primary sclerosing cholangitis and inflammatory bowel disease

Objective: To explore disease characteristics of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) and compare the differences between PSC with and without IBD. Methods: Study design was cross sectional. Forty-two patients with PSC who were admitted from January 2000 to January 2021 were included. We analyzed their demographic characteristics, clinical manifestations, concomitant diseases, auxiliary examination, and treatment. Results: The 42 patients were 11-74(43±18) years of age at diagnosis. The concordance rate of PSC with IBD was 33.3%, and the age at PSC with IBD diagnosis was 12-63(42±17) years. PSC patients with IBD had higher incidences of diarrhea and lower incidences of jaundice and fatigue than in those without IBD (all P<0.05). Alanine aminotransferase, total bilirubin, direct bilirubin, total bile acid and carbohydrate antigen 19-9 levels were higher in PSC patients without IBD than in those with IBD (all P<0.05). The positive rates for antinuclear antibodies and fecal occult blood were higher in PSC patients with IBD than in those without IBD (all P<0.05). Patients with PSC complicated with ulcerative colitis mainly experienced extensive colonic involvement. The proportion of 5-aminosalicylic acid and glucocorticoid application in PSC patients with IBD was significantly increased compared with that of PSC patients without IBD (P=0.025). Conclusions: The concordance rate of PSC with IBD is lower at Peking Union Medical College Hospital than in Western countries. Colonoscopy screening may benefit PSC patients with diarrhea or fecal occult blood-positive for early detection and diagnosis of IBD.

S956 A Meta-Analysis of Colonic Involvement in Ulcerative Colitis Among Asian Countries

Introduction: Ulcerative Colitis (UC) is a chronic inflammatory non-fatal disease usually found in the large intestine and rectum. Over the years the incidence and prevalence of UC has been lower in Asia when compared to the Western World. However, new studies in Asia are showing an increase in the incidence of UC over the past 2 decades. Here we aim to assess the incidence and manifestations of Ulcerative Colitis across multiple countries in Asia. Methods: An extensive meta-analysis on Ulcerative colitis patients was performed comparing articles from different parts of Asia, and R software was used 2 compile the data. In addition, the patient's data regarding colonic involvement was reviewed. Patient’s data was then matched using propensity score matching in the R software. Results: Incidence of rectal involvement was high among the Chinese and Indian population (30.30% China vs. 5.56% Hong Kong vs. 2.53% Singapore vs.19.80% Korea vs. 31.82% India, p:0.023 95%CI). Left-sided ulcerated colitis was predominant among the Chinese population (38.28% China vs. 5.26% Hong Kong vs. 0.93% Singapore vs. 13.80% Korea vs. 10.82% India, p:0.033 95%CI). Extensive colonic manifestation involving most of the colon was seen in the Indian population compared to other nationalities (10.01% China vs. 9.09% Hong Kong vs. 7.27 % Singapore vs. 20.80% Korea vs. 44.10 % India, p < 0.01 95%CI). Conclusion: There are a multitude of factors that may be contributing to the rise of both the incidence and prevalence of UC in Asian Countries. These factors include westernization of lifestyle, changes in diet, increased use of modern medicine from the traditional homeopathic modalities, and/or industrialization of society. As you can see from our study, the incidence, prevalence and manifestations even within Asia vary among the countries. A study conducted in 2013 which compared Singapore, Malaysia, and India found that Indians not only had a higher prevalence of UC but also had more extensive disease. In our study, we found that rectal involvement was highest among Chinese and Indians. However, extensive colonic involvement was seen at a significantly higher rate in Indians compared to the rest.

PB2125: LYMPHOMATOID PAPULOSIS-LIKE (LYP-LIKE) AFTER BRENTUXIMAB VEDOTIN-CHP (BV-CHP) TREATMENT FOR ALK-NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA (ALCL)

Background: Lymphomatoid papulosis is an indolent form of CD30 primary cutaneous lymphoproliferative disorder characterized for recurrent crops of self-healing papular nodular lesions. Histological findings may overlap with those in primary cutaneous ALCL so clinical features and evolution determine the appropriate therapeutic approach. Most cases of LyP don’t require any treatment, but PUVA or low-dose oral methotrexate can reduce skin lesions. LyP-like is uncommon after a systemic ALCL. BV-CHP has become the new standard front-line treatment for ALCL in the last years; some aspects of the biological and clinical behavior of the disease with this new therapy are still under research. Aims: NA Methods: NA Results:Patient 1: 45 years female, diagnosed in January/20 with ALK-negative ALCL stage IV-A, IPI 3, involving multiple supra- and infradiaphragmatic lymphadenopathies, spleen, skin, bone and bone marrow. The diagnosis was performed by skin biopsy of an extensive ulcerated mass in the right chest area. FISH showed no rearrangements of DUSP22 and TP63. BV-CHP was started in January/20, achieving PR by PET-CT after 3 cycles. She completed 6 cycles. Four weeks after the last dose of chemotherapy she developed several papular skin lesions in the trunk and extremities. The skin biopsy was reported as ALCL. PET-CT showed metabolic CR at that time. After 3 weeks, the skin lesions spontaneously disappeared and she underwent ASCT conditioned with BEAM in July/20. Two months later, she developed new skin lesions and a new biopsy showed nonspecific findings: perivascular lymphocytic dermatitis with epidermal spongiotic changes. PET-CT showed two enlarged axillary lymphadenopathies with increased activity. A watch and wait strategy was adopted, until September/21 when she relapsed involving multiple lymphadenopathies, bone, spleen and new papulo-necrotic skin lesions. Skin biopsy showed a CD30+ lymphoprolipherative disorder. She received 3 cycles of ESHAP achieving PR, and an haploidentical stem cell transplantation was performed in January/22. Two months after transplant, the patient has no signs of disease and no skin lesions. Patient 2: 62 years male, diagnosed in August/21with systemic ALK-negative ALCL stage IV-B, IPI 3, with supra- and infradiaphragmatic lymphadenopathies and extensive colonic involvement. DUSP22-IRF4 and TP63 rearrangements were assessed, showing no abnormalities. Bone marrow and skin were not affected. He started front-line treatment with BV-CHP in September/21, with metabolic CR in the interim PET-CT after 4 cycles. He completed 6 cycles with good tolerance until late December/21. One month later, he developed papular and papulo-necrotic skin lesions in different evolutionary stages, affecting trunk, extremities and scalp. Skin biopsy was performed, showing a CD30+ lymphoprolipherative disorder. Another PET-CT demonstrated systemic CR. Clinicopathological findings were consistent with lymphomatoid papulosis. The patient underwent an ASCT as consolidation treatment. Currently, the skin lesions have involuted spontaneously. Image:Summary/Conclusion: These two similar cases illustrate an unusual scenario after systemic ALK-negative ALCL, both developed within weeks after frontline chemotherapy with BV-CHP. Diagnosis and therapeutic decisions are challenging. Further experience with this new regimen will reveal whether the addition of BV may play a role in the development of this condition, and whether the clinical course is the same as primary cases of LyP or precedes a relapse of systemic lymphoma.

Incidence, Disease Course, and Medical Treatment of a Danish Population-Based Cohort of Very Early-Onset Inflammatory Bowel Disease

Background and Aims. In very early-onset IBD patients (VEO-IBD), studies have shown an incidence ranging from 0.4 to 2.1/100,000, extensive disease location, and a corresponding difficult and debatable treatment. We therefore aimed to investigate the incidence and medical and surgical treatment of VEO-IBD in a well-defined Danish population-based cohort. Methods. All VEO-IBD patients, defined as an IBD diagnosis before 6 years of age, were included from the Capital Region and the Zealand Region in 2015-2020. Demographic and clinical data including medical and surgical treatment were systematically extracted from the patient files. Results. Forty VEO-IBD patients were identified, 11 diagnosed with CD, 23 UC, and 6 IBD-U. The incidence rate of VEO-IBD was 2.0/100,000 (95% CI 0.8-5.9). All VEO-IBD patients except one had extensive colonic involvement or pancolitis. A total of 34 (85.0%) and 23 (57.5%) of the VEO-IBD patients received immunomodulators and/or biologicals, respectively. The cumulative risks of receiving immunomodulators and/or biologicals after 1/3/5 years was 55.3%/86.8%/90.1% and 36.8%/45.9%/57.0%, respectively. During follow-up, six VEO-IBD patients (15.0%) were treated with vedolizumab—although off-label for this age group—as second-line biological therapy. Four patients (17.4%) with UC had a colectomy. Two colectomised patients were treated with vedolizumab. Conclusion. Our population-based study showed an incidence of VEO-IBD comparable with the incidence in other countries. The population were treated intensively with immunomodulators and biologicals—including off-label vedolizumab—and compared to other studies had the same risk of undergoing IBD-related surgeries.

Elderly Patients with Moderate-To-Severe Ulcerative Colitis Are More Likely to Have Treatment Failure and Adverse Outcome

Background and Aim: The aim of this study was to compare therapeutic responses and prognosis between elderly and nonelderly ulcerative colitis (UC) patients with moderate-to-severe activity. Methods: 148 UC patients with moderate-to-severe activity hospitalized between 2000 and 2019 were enrolled consecutively, including 74 patients with the age of diagnosis over 60 years and 74 patients diagnosed less than 60 years. Patients were matched by gender, duration (±15%), disease activity, and admission time (±1 year). They were followed up until the latest medical record or December 2019. The primary outcome was UC-related colectomy or death. Results: 148 patients were followed over median 37.5 months. For steroid use, 76.8% of elderly UC patients were responsive, lower than that in adult group (85.7%). A decreased level of clinical activity index (2.0 [−1.5 to 4.00] vs. 6.0 [3.0–8.0], p < 0.001), reduction of C-reactive protein (23.9 [3.5–65.5] vs. 27.8 [9.7–58.1] mg/L), and erythrocyte sedimentation rate (9.0 [−1.3 to 30.5] vs. 15.5 [3.8–36.5] mm/h) at 4 weeks after steroid induction was less obvious in the elderly. More elderly patients manifested steroid dependence and resistance. 28.4% of elderly UC patients took colectomy, remarkably more than adult patients (12.2%), which also occurred earlier (8.0 [0.5–44.75] vs. 39.5 [12–57.38] months, p = 0.001). Aging (hazard ratio [HR] 2.868, 95% confidence interval [CI]: 1.290–6.375, p = 0.01), male, steroid resistance, and occurrence of complications were independently related to colectomy. The rate of serious infections was significantly higher in the elderly (55.4% vs. 35.1%, p = 0.013), mainly including cytomegalovirus infection, bacterial infection, and extraintestinal infection. Aging (odds ratio [OR] 2.774, 95% CI: 1.355–5.675, p = 0.015), extensive colonic involvement, steroid resistance, and biologics usage were independently associated with a high risk of concomitant infections. Conclusion: Elderly patients with moderate-to-severe UC experienced more treatment failure and increased risk of UC-related colectomy, mortality, and severe infections, predicting demand for more strict and individualized management.

Therapeutic Drug Monitoring-guided High-dose Infliximab for Infantile-onset Inflammatory Bowel Disease: A Case Series.

Very early-onset inflammatory bowel disease (IBD) and specifically infantile-onset IBD patients, are characterized by high rates of extensive colonic involvement and decreased response rate to standard therapeutic regimens, including infliximab (IFX). We present a case series of 4 patients with infantile-onset IBD achieving clinical and biologic remission, after treatment with therapeutic drug monitoring (TDM)-guided accelerated high-dose IFX therapy. All patients were treated with accelerated high-dose IFX induction of up to 22 mg/kg. In 3 of these patients, accelerated high-dose IFX was used following failure of intensified standard dose induction. All patients achieved remission following re-induction.We suggest that children with infantile-onset IBD may require a TDM-guided accelerated high-dose IFX induction and maintenance treatment in order to achieve and maintain remission. Personalized approach in these patients is essential in order to prevent underdosing and to avoid inappropriate interpretation of treatment failure.

P231 Epidemiological profile and long-term outcomes from a large PSC-IBD cohort

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic disease associated with inflammatory bowel diseases (IBD) in 70% of cases.1 When combined, they present as one distinct phenotypical disease referred to as PSC-IBD with milder clinical course, despite more extensive colonic involvement and an increased risk of malignancies. The aim of this study was to assess clinical features and long-term outcomes of PSC-IBD patients from a quaternary hospital in Brazil. Methods We retrospectively reviewed all PSC-IBD patients registered and followed-up in our outpatient clinic between January 2000 and July 2019. Conventional colonoscopic and histological criteria were used to diagnose IBD, whereas radiographic or histological criteria for PSC. Medical records were abstracted for the following data: demographic characteristics; duration, extent, and treatment of IBD; duration, extent, and treatment of PSC; colorectal neoplasia (dysplasia and cancer); surgical treatment for IBD; liver transplantation and death. Results In total, 92 patients with concurrent PSC and IBD were identified. Of 92 cases, 80 (87%) had ulcerative colitis (UC) and 12 (13%) were diagnosed with Crohn’s disease (CD). There was a slight predominance of male, 51 (55%). The mean age at both IBD and PSC diagnosis was 31 and 35 years, respectively. Most of them were diagnosed with IBD prior to PSC (53%). The mean IBD duration was 15 years and 10 years in PSC subjects. The prevalence of pancolitis in UC patients was 91%. All CD cases presented ileocolonic involvement. Present or past smoking history was reported in 6% of the cohort. Aminosalicylates were the most common treatment used for IBD in 59 patients (64%). 15 of them (16%) were on monotherapy with immunobiologics and 7 patients (8%) were on combotherapy. Only 3 subjects were on anti-integrin. In our cohort, 61 cases (66%) were treated with ursodeoxycholic acid. Colorectal neoplasia and cholangiocarcinoma were observed in 6 (7%) and 3 patients (3.3%), respectively. Colorectal dysplasia was found in 20 subjects (22%) on a routine colonoscopy. Overall, 17 patients (19%) required proctocolectomy and 11 cases (12%) have undergone orthotopic liver transplant. There were 12 deaths, mainly PSC and cancer-related. Conclusion Herein we present the largest cohort of concomitant PSC and IBD in Latin America. In our centre, we have found higher rates of extensive IBD, although few of them required colectomy. The present data on cancer and dysplasia are consistent with reports in the literature. Reference

Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis

BackgroundImmune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes.MethodsOur study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2 mm, larger than 1 cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes.ResultsA total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60 years. Median time from ICPI initiation to IDC was 7 weeks. Fifty-three percent had grade 3–4 diarrhea, and 32% grade 3–4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P = 0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7 days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7 days of IDC onset (P = 0.026 and P = 0.053, respectively). Patients who underwent endoscopy > 30 days of symptom onset required longer duration of steroids (P = 0.02), had more recurrent symptoms (P < 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy ≤30 days (P = 0.03). High-risk features were associated with more frequent (P = 0.03) and longer duration (P = 0.02) hospitalization and infliximab/vedolizumab requirement (P < 0.01). Patients with active histological inflammation had more recurrence (P < 0.01) and repeat endoscopy (P < 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00–1.01; P < 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68–9.01; P < 0.01).ConclusionHigh risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms.

Enhanced Contribution of HLA in Pediatric Onset Ulcerative Colitis.

The genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59). To study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array. SNP2HLA was used to impute classical HLA alleles and their corresponding amino acids, and the results are compared with adult onset UC. HLA explained the almost entire association signal, dominated with 191 single nucleotide polymorphisms (SNPs) (p = 5 x 10-8 to 5 x 10-10). Although very small effects, established SNPs in adult onset UC loci had similar direction and magnitude in pediatric onset UC. SNP2HLA imputation identified HLA-DRB1*0103 (odds ratio [OR] = 6.941, p = 1.92*10-13) as the most significant association for pediatric UC compared with adult onset UC (OR = 3.59). Further conditioning showed independent effects for HLA-DRB1*1301 (OR = 2.25, p = 7.92*10-9) and another SNP rs17188113 (OR = 0.48, p = 7.56*10-9). Two HLA-DRB1 causal alleles are shared with adult onset UC, while at least 2 signals are unique to pediatric UC. Subsequent stratified analyses indicated that HLA-DRB1*0103 has stronger association for extensive disease (E4: OR = 8.28, p = 4.66x10-10) and female gender (OR = 8.85, p = 4.82x10-13). In pediatric onset UC, the HLA explains almost the entire genetic associations. In addition, the HLA association is approximately twice as strong in pediatric UC compared with adults, due to a combination of novel and shared effects. We speculate the paramount importance of antigenic stimulation either by infectious or noninfectious stimuli as a causal event in pediatric UC onset.

Inflammatory bowel disease in chronic granulomatous disease: An emerging problem over a twenty years' experience.

Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocytes, characterized by life-threatening infections and hyperinflammation. Due to survival improvement, inflammatory bowel disease (IBD) is becoming increasingly relevant. Here, we report our 20year experience. We retrospectively analyzed clinic, endoscopic, and histologic features, as well as the management of CGD-IBD patients referred to the Bambino Gesù Children's Hospital in Rome, Italy. Of 20 patients with CGD, 9 presented with CGD-IBD at diagnosis and/or during follow-up. Symptoms occurred at a median age of 16years (range 3.2-42), with a median delay of 6months for endoscopic confirmation. Patients mainly complained of nonspecific diarrhea (55%), with discrepancy between symptom paucity and severe endoscopic appearance, mainly represented by extensive colonic involvement (44%). Histology revealed at least 2 characteristic features (epithelioid granulomas, pigmented macrophages, and increased eosinophils) in 78% of patients. Eight of 9 patients received oral mesalamine, and 5 required systemic steroids. One patient received azathioprine due to steroid dependence. No patient required biological therapy or surgery. Clinical remission was obtained in all patients, but the majority complained of mild relapses. Two episodes of severe infection occurred early after steroid therapy. Penetrance of CGD-IBD increases with age. Clinical manifestations may be subtle, and clinicians should have a low threshold to recommend endoscopy. Treatment with NSAIDs and/or steroids achieves a good response, but relapses usually occur. Infection surveillance is mandatory during treatment, to prevent opportunistic infections. A close collaboration between pediatric immunologists and gastroenterologists is pivotal, including combined follow-up.

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features.

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.

Budesonide for induction of remission in Crohn's disease.

Corticosteroids are commonly used for the induction of remission in Crohn's disease. However, traditional corticosteroids can cause significant adverse events. Budesonide is an alternative glucocorticoid with limited systemic bioavailability. The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease. The following electronic databases were searched up to June 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. Randomised controlled trials comparing budesonide to a placebo or active comparator were considered for inclusion. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Meta-analysis was performed using RevMan 5.3.5 software. The primary outcome was induction of remission (defined by a Crohn's disease activity index (CDAI) < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal. We calculated the relative risk (RR) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome and the mean difference and corresponding 95% CI for each continuous outcome. Data were analyzed on an intention-to-treat basis. A random-effects model was used for the pooled analyses. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was evaluated using the GRADE criteria. Fourteen studies (1805 patients) were included: Nine (779 patients) compared budesonide to conventional corticosteroids, three (535 patients) were placebo-controlled, and two (491 patients) compared budesonide to mesalamine. Ten studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to open label design. One study was judged to be at high risk of bias due to selective reporting. After eight weeks of treatment, 9 mg budesonide was significantly more effective than placebo for induction of clinical remission. Forty-seven per cent (115/246) of budesonide patients achieved remission at 8 weeks compared to 22% (29/133) of placebo patients (RR 1.93, 95% CI 1.37 to 2.73; 3 studies, 379 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (144 events). Budesonide was significantly less effective than conventional steroids for induction of remission at eight weeks. Fifty-two per cent of budesonide patients achieved remission at week 8 compared to 61% of patients who received conventional steroids (RR 0.85, 95% CI 0.75 to 0.97; 8 studies, 750 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to risk of bias. Budesonide was significantly less effective than conventional steroids among patients with severe disease (CDAI > 300) (RR 0.52, 95% CI 0.28 to 0.95). Studies comparing budesonide to mesalamine were not pooled due to heterogeneity (I(2) = 81%). One study (n = 182) found budesonide to be superior to mesalamine for induction of remission at 8 weeks. Sixty-eight per cent (63/93) of budesonide patients were in remission at 8 weeks compared to 42% (37/89) of mesalamine patients (RR 1.63, 95% CI 1.23 to 2.16). The other study found no statistically significant difference in remission rates at eight weeks. Sixty-nine per cent (107/154) of budesonide patients were in remission at 8 weeks compared to 62% (132/242) of mesalamine patients (RR 1.12, 95% CI 0.95 to 1.32). Fewer adverse events occurred in those treated with budesonide compared to conventional steroids (RR 0.64, 95% CI 0.54 to 0.76) and budesonide was better than conventional steroids in preserving adrenal function (RR for abnormal ACTH test 0.65, 95% CI 0.55 to 0.78). Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression with budesonide is lower. The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-ASA products.

Relationship Between Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Inflammatory Bowel Disease Type and Activity

Neutrophil gelatinase associated lipocalin (NGAL) is a recently identified molecule, which is bacteriostatic, has tissue destructive effects and is pro-inflammatory with chemoattractant molecule binding properties. Our aim was to investigate the relationship between serum NGAL levels and the type and level of disease activity of IBD. A total of 92 patients [43 with Crohn's disease (CD) and 49 with ulcerative colitis (UC)], and 30 age- and sex-matched healthy controls (HC) were included in this study. Serum NGAL levels were measured using ELISA. Serum NGAL levels were elevated in the IBD group [median 171, range (57-312) ng/mL] compared to the HC group [107 (45-234) ng/mL] (p<0.0001) and were elevated in UC patients [188 (74-312) ng/mL] compared to CD patients [168 (57-279) ng/mL] (p=0.006). When NGAL levels were further analysed based on localization of the CD and UC, the levels in ulcerative pancolitis [233 (144-312) ng/mL] were significantly higher (p=0.004) than the left-sided colitis [156 (103-309) ng/mL]. Similarly, NGAL levels were significantly higher in colonic CD [207 (125-249) ng/mL] than ileal CD [114 (78-210) ng/mL], and also in ileocolonic CD [198 (57-279) ng/mL] than ileal CD (p=0.033). When CD and UC groups were further categorized as active and inactive according to clinical and endoscopic activity indices, serum NGAL concentrations did not differ between inquiescent versus active stages. When a cut-off level of 129 ng/mL was used to distinguish IBD from HC, a sensitivity of 76.1% and a specificity of 60.9% was reached. The serum NGAL levels in the IBD group was significantly higher than the HC group. Serum NGAL levels were higher in more extensive colonic involvement.

Gallbladder carcinoma in a pregnant patient with Crohn's disease complicated with gallbladder involvement

Primary gallbladder (GB) carcinoma and Crohn's disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. A 34-year-old female at 6 wk gestation with a 21 year history of CD of uncertain extent presented with 3 mo of diarrhea, urgency and abdominal pain. During work-up, she was found to have elevated transaminases and an abnormal alkaline phosphatase. Imaging revealed two gallbladder polyps both greater than 1 cm in size. Resection and histological evaluation was consistent with Crohn's involvement of the GB, poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Six cases of CD involving the GB, two cases of primary GB carcinoma in CD, and ten cases of cholangiocarcinoma in pregnancy have been published. This is the only case that describes all three factors. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement of disease, the absence of cholelithiasis, and pre-existing gallbladder disease (primary sclerosing cholangitis and gallbladder polyps). Pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood nor is the contribution of pregnancy to the spread of disease. Chronic inflammation and immunosuppression compounded by hormonal influence is implicated.

Primary Gallbladder Carcinoma in a Pregnant Patient with Crohnʼs Disease Complicated with Gallbladder Involvement

Purpose: Primary gallbladder (GB) carcinoma and Crohn's disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. Case: A 34-year-old female at 6 weeks gestation with a 21 year history of CD of uncertain extent presented with 3 months of diarrhea, urgency, and abdominal pain. Her disease had been indolent for the majority of her life. She was adherent to her medications, mesalamine and mercaptopurine, as needed at times of symptoms. Sigmoidoscopy showed mild patchy colitis of the descending and sigmoid colon with rectal sparing. Pathology showed moderately active chronic colitis with crypt distortion and cryptitis without granuloma. She was started on oral and topical mesalamine. Initial labs included abnormal alkaline phosphatase 515 U/L, AST 96 U/L, and ALT 181 U/L. Further labs included a negative anti-mitochondrial antibody (AB), anti-smooth muscle AB, celiac and viral hepatitis serologies and anti-nuclear AB. A non-contrast MRCP was obtained revealing two hypointense smooth margined masses with small stalks in the neck and fundus of the GB, 1.4 × 1.8 cm and 1.4 × 2.3 cm, respectively. No GB wall thickening, cholilithiasis, ductal dilation, strictures, or liver parenchymal abnormalities were present. Laparoscopic cholecystecomy was performed at 18 wks gestation. Histology revealed a poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and an adjacent tubulovillous adenoma with highgrade dysplasia without nodal involvement (stage pT2N0). Additionally, there was widespread epithelial dysplasia in the gallbladder with acute superficial inflammation, transmural chronic inflammation with numerous plasma cells and one granuloma consistent with CD. Muscularis propria invasion prompted partial liver resection and portal lymphadenectomy, revealing matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Liver tissue was negative for primary sclerosing cholangitis. Conclusion: Seven cases of CD involving the GB and 3 cases of primary GB carcinoma in CD have been published. This is the only case that describes both. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement, and absence of cholelithiasis. Adnomatous GB polyps and pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood; however, longstanding immunosuppression is implicated.

Differences in the location and activity of intestinal Crohn’s disease lesions between adult and paediatric patients detected with MRI

To prospectively compare paediatric patients (PP) and adult patients (AP) affected by Crohn's disease (CD) in terms of the location and activity of intestinal lesions. Forty-three children (mean age 15years) and 43 adults (mean age 48years) with proven CD underwent magnetic resonance enterography (MRE) to localise lesions and detect their activity in 9 segments of the small and large bowel. The results were analysed on a per patient and per segment basis. Ileo-colonoscopy was performed in all patients. P values less than 0.05 were considered statistically significant. Involvement of terminal ileum was significantly different in the two groups: observed in 100% of AP (43/43) versus 58% (23/43) of PP (P < 0.0001). Conversely, the colon was diseased in 84% of PP versus 64% of AP. In particular, left colonic segments were significantly more involved in PP (descending colon 53% versus 21%, P < 0.01; rectum 67% versus 23%, P < 0.0001; sigmoid colon 56% versus 37%, not significant), whereas caecal involvement was equal in both groups. In children the maximal disease activity was found in left colonic segments, whereas in adults it was in the terminal ileum. MRE detected significant differences between the two populations, showing a more extensive and severe involvement of the left colon in children but the distal ileum in adults. • MRI is useful for assessing Crohn's disease in adult and paediatric patients. • Adult and paediatric patients show different intestinal involvement on MRI. • The distal ileum is maximally involved in adults vs. the left colon in children. • The causes of the severe left colonic disease in children are unknown. • The extensive colonic involvement in children has clinical-diagnostic implications.

Colorectal Cancer Chemoprevention by Mesalazine and Its Derivatives

Patients with inflammatory bowel disease (IBD) face an increased lifetime risk of developing colorectal cancer (CRC). Independent factors associated with increased risk include long disease duration, extensive colonic involvement, young age at onset of IBD, severity of inflammation, primary sclerosing cholangitis, backwash ileitis, and a family history of CRC, thus emphasising the role of intestinal inflammation as an underlying mechanism. This notion is also supported by the demonstration that the use of certain drugs used to attenuate the ongoing mucosal inflammation, such as mesalazine, seems to associate with a reduced incidence of colitis-associated CRC. In the last decade, work from many laboratories has contributed to delineate the mechanisms by which mesalazine alters CRC cell behaviour. In this paper, we review the available experimental data supporting the ability of mesalazine and its derivatives to interfere with intracellular signals involved in CRC cell growth.

The −A2518G Polymorphism of Monocyte Chemoattractant Protein-1 Is Associated With Crohn's Disease

The -A2518G variation in monocyte chemoattractant protein (MCP)-1 gene promoter has been associated with autoimmune diseases. Our aim was to investigate the gene polymorphism and MCP-1 plasma levels in patients with inflammatory bowel disease (IBD). Family-based and case-control association analyses of the -A2518G polymorphism (rs1024611) were performed in 1,936 subjects (770 patients with Crohn's disease (CD), 316 patients with ulcerative colitis (UC), 302 healthy relatives (151 CD trios), and 548 healthy controls (HCs)). Extensive gene sequencing was also undertaken, and a further six single-nucleotide polymorphisms (SNPs) were genotyped in 435 CD patients and 189 HCs. MCP-1 protein plasma levels in 234 CD patients, 117 UC patients, and 108 HCs were assessed by an immunosorbent assay. Five SNPs in strong linkage disequilibrium (D'>0.85) were associated with CD, with the strongest signal found at the -A2518G SNP. The frequency of the G allele was significantly lower in CD patients (22.1%), compared with HCs (29.8%), both at case-control (P=6 x 10(-6)) and at transmission disequilibrium test analyses (T/U 41/88; P=4 x 10(-4)). No difference in alleles (26.1%) and genotype frequencies were found in UC patients. MCP-1 plasma levels in CD and UC patients were similar to those in HCs (P=0.38), irrespective of disease activity, or MCP-1 genotypes. However, 30 CD (13%) and 20 UC patients (17%) with extensive colonic involvement had plasma levels significantly higher than HCs (P=0.02). The -A2518G polymorphism seems to be associated with CD but does not influence MCP-1 plasma levels, which in contrast are increased in UC and CD with extensive colonic involvement.