Neurofibromatosis Type 1 Presenting as Bleeding Jejunal Gastrointestinal Stromal Tumour.

Introduction: Gastrointestinal stromal tumours (GISTs) are an important, though uncommon, cause of obscure gastrointestinal bleeding and may rarely be associated with genodermatoses such as neurofibromatosis type 1 (NF1). NF1-related GISTs have unique phenotypic features compared with sporadic GISTs and may elude diagnosis due to their predilection for the small bowel. Case Presentation: We report a case of a 45-year-old Singaporean woman with café-au-lait macules and cutaneous neurofibromas who presented with occult obscure gastrointestinal bleeding and was eventually discovered to have a bleeding jejunal GIST. This finding, considered together with her cutaneous signs, eventually led to the diagnosis of NF1. Conclusion: Genodermatoses and their gastrointestinal complications are likely under-reported in adult Southeast Asian populations and deserve greater awareness from gastroenterologists practising in this region.

Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).

OBJECTIVE: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS: There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS: We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

Superior Mesenteric Artery Syndrome: A Potentially Fatal but Reversible Gastrointestinal Manifestation of Systemic Sclerosis.

Superior mesenteric artery syndrome (SMAS) is a rare gastrointestinal disorder characterised by vascular compression of the third part of the duodenum, in the angle between the superior mesenteric artery (SMA) and the abdominal aorta. It presents as an uncommon cause of upper gastrointestinal obstruction. In patients with systemic sclerosis (SSc), gastrointestinal involvement may result in oesophageal dysmotility, gastroesophageal reflux disease (GERD), gastroparesis, small intestinal bacterial overgrowth (SIBO), chronic intestinal pseudoobstruction (CIPO), and fecal incontinence. Malnutrition may thus result in weight loss and reduced mesenteric and retroperitoneal adipose tissue, decreasing the angle between the SMA and aorta causing SMAS. Enteral or parenteral feeding can potentially reverse SMAS in SSc. We report a case of SMAS in an elderly female with SSc and concurrent gastrointestinal involvement, and discuss the important management considerations and potential adverse outcomes when untreated.

An intronic FTO variant rs16952570 confers protection against thiopurine-induced myelotoxicities in multiethnic Asian IBD patients.

Thiopurines are used in the treatment of inflammatory bowel disease (IBD) but remain clinically challenging to manage due to wide interpatient variability in clinical outcomes and adverse events. Apart from genetic variants in thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) genes, polymorphisms in FTO alpha-ketoglutarate dependent dioxygenase (FTO) were found predictive of thiopurine-induced leukopenia, albeit with conflicting results. To clarify the role of FTO variants in a multiethnic Asian IBD cohort, we recruited 149 patients on thiopurine-based therapy and genotyped two FTO variants p.Ala134Thr (rs79206939) and rs16952570 T > C using Sanger sequencing. FTO p.Ala134Thr (rs79206939) was non-polymorphic and absent whereas intronic rs16952570 T > C was equally prevalent in Chinese (22%) and Indians (18%) and higher in Malays (28%). Higher nadir white blood cell (WBC) and absolute neutrophil count (ANC) levels were observed in patients harboring FTO rs16952570 CC genotypes compared with TT carriers at 4, 8, and 12 weeks after start of thiopurine therapy (P < 0.05). A similar trend was observed in patients carrying the previously well-characterized NUDT15 rs116855232 wild-type CC genotypes. Further in silico analysis suggests that FTO variants linked to rs16952570, particularly rs74018601, may play a regulatory role in altering the FTO expression. The findings from this study indicate a novel protective association with the FTO variant rs16952570 CC genotype and hematological parameters.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer.

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%). Several IMs exhibited hypermethylation at DNA methylation valleys; however, IMs generally lack intragenic hypomethylation signatures of advanced malignancy. IM patients with shortened telomeres and chromosomal alterations were associated with subsequent dysplasia or GC; conversely patients exhibiting normal-like epigenomic patterns were associated with regression.

Predictive role of NUDT15 variants on thiopurine-induced myelotoxicity in Asian inflammatory bowel disease patients.

BACKGROUND: Genetic variants of TPMT and NUDT15 have been reported to predict the inter-patient variability in response and toxicity profiles of patients receiving thiopurine therapy. However, the clinical utility of TPMT genotyping in guiding thiopurine doses has been questionable, in part due to underlying differences in the prevalence of TPMT variants in both Caucasian and Asian populations. Several NUDT15 variants have been associated with thiopurine-induced leukopenia, particularly in Asian cohorts. So far, none have been reported in a multiethnic Asian population. AIM: To investigate the associations between TPMT and NUDT15 variants with thiopurine-induced myelotoxicity in 129 Asian inflammatory bowel disease patients. MATERIALS & METHODS: Pyrosequencing was performed to screen for TPMT and NUDT15 variants. Intracellular steady-state metabolite concentrations were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Significant declines in nadir white blood cell, absolute neutrophil count and platelet counts were observed with increasing copy numbers of the risk T allele at NUDT15 c.415C>T locus (overall p < 0.05) within 4, 8 and 12 weeks and 6 months after thiopurine initiation. Patients with low and intermediate NUDT15 activity, as inferred from haplotype pairs, had significantly higher risks of leukopenia (p = 0.000253) and neutropenia (p = 0.002) compared with patients with normal NUDT15 activity. CONCLUSION: These findings highlight the critical relevance of NUDT15 pharmacogenetics in predicting for thiopurine-induced myelotoxicity and confirm the lack of significance of TPMT variants in Asian inflammatory bowel disease patients.

Aminosalicylates for induction of remission or response in Crohn's disease.

BACKGROUND: Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in these patients. OBJECTIVES: To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. SEARCH METHODS: We searched PubMed, EMBASE, MEDLINE and the Cochrane Central Library from inception to June 2015 to identify relevant studies. There were no language restrictions. We also searched reference lists from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2015) of the American Gastroenterological Association and American College of Gastroenterology. SELECTION CRITERIA: Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality was independently performed by the investigators and any disagreement was resolved by discussion and consensus. We assessed methodological quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Secondary outcomes included mean Crohn's disease activity index (CDAI) scores, adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes we calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (CI) using a random-effects model. For continuous outcomes we calculated the mean difference (MD) and 95% CI using a random-effects model. Sensitivity analyses based on a fixed-effect model and duration of therapy were conducted where appropriate. MAIN RESULTS: Twenty studies (2367 patients) were included. Two studies were judged to be at high risk of bias due to lack of blinding. Eight studies were judged to be at high risk of bias due to incomplete outcomes data (high drop-out rates) and potential selective reporting. The other 10 studies were judged to be at low risk of bias. A non-significant trend in favour of sulfasalazine over placebo for inducing remission was observed, with benefit confined mainly to patients with Crohn's colitis. Forty-five per cent (63/141) of sulfasalazine patients entered remission at 17-18 weeks compared to 29% (43/148) of placebo patients (RR 1.38, 95% CI 1.00 to 1.89, 2 studies). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (106 events). There was no difference between sulfasalazine and placebo in adverse event outcomes. Sulfasalazine was significantly less effective than corticosteroids and inferior to combination therapy with corticosteroids (RR 0.64, 95% CI 0.47 to 0.86, 1 study, 110 patients). Forty-three per cent (55/128) of sulfasalazine patients entered remission at 17 to 18 weeks compared to 60% (79/132) of corticosteroid patients (RR 0.68, 95% CI 0.51 to 0.91; 2 studies, 260 patients). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (134 events). Sulfasalazine patients experienced significantly fewer adverse events than corticosteroid patients (RR 0.43, 95% CI 0.22 to 0.82; 1 study, 159 patients). There was no difference between sulfasalazine and corticosteroids in serious adverse events or withdrawal due to adverse events. Olsalazine was less effective than placebo in a single trial (RR 0.36, 95% CI 0.18 to 0.71; 91 patients). Low dose mesalamine (1 to 2 g/day) was not superior to placebo for induction of remission. Twenty-three per cent (43/185) of low dose mesalamine patients entered remission at week 6 compared to 15% (18/117) of placebo patients (RR = 1.46, 95% CI 0.89 to 2.40; n = 302). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to risk of bias (incomplete outcome data) and sparse data (61 events). There was no difference between low dose mesalamine and placebo in the proportion of patients who had adverse events (RR 1.33, 95% CI 0.91 to 1.96; 3 studies, 342 patients) or withdrew due to adverse events (RR 1.21, 95% CI 0.75 to 1.95; 3 studies, 342 patients). High dose controlled-release mesalamine (4 g/day) was not superior to placebo, inducing a clinically non significant reduction in CDAI (MD -19.8 points, 95% CI -46.2 to 6.7; 3 studies, 615 patients), and was also inferior to budesonide (RR 0.56, 95% CI 0.40 to 0.78; 1 study, 182 patients, GRADE = low). While high dose delayed-release mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02, 95% CI 0.75 to 5.45; 1 study, 38 patients, GRADE = very low), no significant difference in efficacy was found when compared to conventional corticosteroids (RR 1.04, 95% CI 0.79 to 1.36; 3 studies, 178 patients, GRADE = moderate) or budesonide (RR 0.89, 95% CI 0.76 to 1.05; 1 study, 307 patients, GRADE = moderate). However, these trials were limited by risk of bias (incomplete outcome data) and sparse data (small numbers of events). There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Adverse events that were commonly reported included headache, nausea, vomiting, abdominal pain and diarrhea. AUTHORS' CONCLUSIONS: Sulfasalazine is only modestly effective with a trend towards benefit over placebo and is inferior to corticosteroids for the treatment of mildly to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3.2 to 4 g/day) is not more effective than placebo for inducing response or remission. However, trials assessing the efficacy of high dose mesalamine (4 to 4.5 g/day) compared to budesonide yielded conflicting results and firm conclusions cannot be made. Future large randomized controlled trials are needed to provide definitive evidence on the efficacy of aminosalicylates in active Crohn's disease.

Asia Pacific Consensus Statements on Crohn's disease. Part 1: Definition, diagnosis, and epidemiology: (Asia Pacific Crohn's Disease Consensus--Part 1).

Inflammatory bowel disease (IBD) was previously thought to be rare in Asia, but emerging data indicate rising incidence and prevalence of IBD in the region. The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology with the goal of developing best management practices, coordinating research, and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis, and management of Crohn's disease. The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses, and treatment availability. It does not intend to be all comprehensive and future revisions are likely to be required in this ever-changing field.

Asia-Pacific consensus statements on Crohn's disease. Part 2: Management.

The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field.

Risk of Major Abdominal Surgery in an Asian Population-based Crohn's Disease Cohort.

BACKGROUND: Crohn's disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. METHODS: This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan-Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. RESULTS: The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9-13.0 yr) and median age at diagnosis 30.5 years (range, 19.5-43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17-40 yr, OR: 2.75, 95% confidence interval [CI], 1.14-7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14-5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20-11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0-58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19-0.78). CONCLUSIONS: Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study.

BACKGROUND AND AIM: The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Aminosalicylates for induction of remission or response in Crohn's disease.

BACKGROUND: Controlled clinical trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in patients with mildly to moderately active Crohn's disease. OBJECTIVES: To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. SEARCH STRATEGY: Separate MEDLINE (1966-July 2010), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 3, 2010) and EMBASE database searches (1985-July 2010) of all relevant English and non-English language articles were performed, followed by manual searches of the reference list from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2010) of the American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG). SELECTION CRITERIA: Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of each selected study was independently performed by the investigators and any disagreement was resolved by discussion and consensus. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Nineteen studies met the inclusion criteria and were analyzed. Pooled relative risks (RR) for inducing remission or clinical response and their 95% confidence intervals were calculated (random effects model) where appropriate. MAIN RESULTS: Sulfasalazine was more likely to induce remission (RR 1.38; 95% CI 1.02 to 1.87; n = 263) compared to placebo with benefit confined mainly to patients with colitis. Sulfasalazine was less effective than corticosteroids (RR 0.66; 95% CI 0.53 to 0.81; n = 260). Olsalazine was less effective than placebo in a single trial. Low dose mesalamine (1 to 2 g/day) was not superior to placebo (RR = 1.46, 95% CI 0.89-2.40; n = 302) and was less effective than corticosteroids. High dose mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02; 95% CI 0.75 to 5.45) or response (Weighted Mean Difference -19.8 points; 95% CI -46.2 to 6.7; n = 615). In a single randomized controlled trial, 5-ASA was inferior to budesonide (RR 0.56; 95% CI 0.40 to 0.78). No statistically significant difference was found between high dose mesalamine and conventional corticosteroids (RR 1.04; 95% CI 0.79 to 1.36; n = 178). However, relatively few patients were available for analysis. There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. AUTHORS' CONCLUSIONS: Sulfasalazine has modest efficacy compared to placebo and is inferior to corticosteroids for the treatment of mild to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3 to 4.5 g/day) is not more effective than placebo for inducing response or remission. High dose mesalamine was inferior to budesonide for inducing remission in a single trial. In conclusion, sulfasalazine shows modest efficacy for the treatment of active Crohn's disease. However, the existing data show little benefit for 5-aminosalicylates.

The Asia-Pacific consensus on ulcerative colitis.

Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia. A multi-disciplinary group developed the consensus statements, reviewed the relevant literature, and voted on them anonymously using the Delphi method. The finalized statements were reviewed to determine the level of consensus, evidence quality and strength of recommendation. Infectious colitis must be excluded prior to diagnosing UC. Typical histology and macroscopic extent of the disease seen in the West is found in the Asia-Pacific region. Ulcerative colitis is increasing in many parts of Asia with gender distribution and age of diagnosis similar to the West. Extra-intestinal manifestations including primary sclerosing cholangitis are rarer than in the West. Clinical stratification of disease severity guides management. In Japan, leukocytapheresis is a treatment option. Access to biologic agents remains limited due to high cost and concern over opportunistic infections. The high endemic rates of hepatitis B virus infection require stringent screening before initiating immune-suppressive agents. Vaccination and prophylactic therapies should be initiated on a case-by-case basis and in accordance with local practice. Colorectal cancer complicates chronic colitis. A recent increase in UC is reported in the Asia-Pacific region. These consensus statements aim to improve the recognition of UC and assist clinicians in its management with particular relevance to the region.

Mechanisms of disease: vitamin D and inflammatory bowel disease.

Until recently, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-the active form of vitamin D-was thought to function primarily as a regulator of calcium and phosphate metabolism. More diverse functionality was indicated by the discovery of the vitamin D receptor in tissues that are not involved in calcium and phosphate homeostasis. Detection of the vitamin D receptor in monocytes and activated T cells has sparked interest in the immunomodulatory properties of vitamin D. Here, we review the role of vitamin D in regulation of the immune system, and evidence for its involvement in the pathogenesis of inflammatory bowel disease.