Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

EUS-Guided Biopsy with a Novel Puncture Biopsy Forceps Needle-Feasibility Study.

Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) or biopsy (FNB) to diagnose lesions in the gastrointestinal tract is common. Demand for histology sampling to identify treatment-specific targets is increasing. Various core biopsy FNB needles to obtain tissue for histology are currently available, however, with variable (37-97%) histology yields. In this multicenter study, we evaluated performance, safety, and user experience of a novel device (the puncture biopsy forceps (PBF) needle). Twenty-four procedures with the PBF needle were performed in 24 patients with a suspected pancreatic lesion (n = 10), subepithelial lesion (n = 10), lymph node (n = 3), or pararectal mass (n = 1). In 20/24 (83%) procedures, the PBF needle yielded sufficient material for interpretation (sample adequacy). In 17/24 (71%), a correct diagnosis was made with the material from the PBF needle (diagnostic accuracy). All participating endoscopists experienced a learning curve. (Per)procedural technical issues occurred in four cases (17%), but there were no adverse events. The PBF needle is a safe and potentially useful device to obtain an EUS-guided biopsy specimen. As the design of the PBF needle is different to core biopsy FNB needles, specific training will likely further improve the performance of the PBF needle. Furthermore, the design of the needle needs further improvement to make it more robust in clinical practice.

Gastroenteric tube feeding: techniques, problems and solutions.

Gastroenteric tube feeding plays a major role in the management of patients with poor voluntary intake, chronic neurological or mechanical dysphagia or gut dysfunction, and patients who are critically ill. However, despite the benefits and widespread use of enteral tube feeding, some patients experience complications. This review aims to discuss and compare current knowledge regarding the clinical application of enteral tube feeding, together with associated complications and special aspects. We conducted an extensive literature search on PubMed, Embase and Medline using index terms relating to enteral access, enteral feeding/nutrition, tube feeding, percutaneous endoscopic gastrostomy/jejunostomy, endoscopic nasoenteric tube, nasogastric tube, and refeeding syndrome. The literature showed common routes of enteral access to include nasoenteral tube, gastrostomy and jejunostomy, while complications fall into four major categories: mechanical, e.g., tube blockage or removal; gastrointestinal, e.g., diarrhea; infectious e.g., aspiration pneumonia, tube site infection; and metabolic, e.g., refeeding syndrome, hyperglycemia. Although the type and frequency of complications arising from tube feeding vary considerably according to the chosen access route, gastrointestinal complications are without doubt the most common. Complications associated with enteral tube feeding can be reduced by careful observance of guidelines, including those related to food composition, administration rate, portion size, food temperature and patient supervision.

Prospective multicenter study evaluating fecal calprotectin in adult acute bacterial diarrhea.

BACKGROUND: Every year, about 2.2 million deaths occur worldwide due to diarrhea. Reliable diagnosis of patients with acute infectious diarrhea remains a formidable challenge to the clinicians. This is the first study reporting use of fecal calprotectin in diagnosing acute diarrhea. The aim was to compare the diagnostic accuracy of fecal calprotectin, fecal lactoferrin, and guaiac-based fecal occult blood test in a diverse group of consecutive patients with acute diarrhea in which routine bacterial stool cultures and cytotoxins for Clostridium difficile were performed. METHODS: This was a prospective case-control multicenter study from January 2004 until October 2007 in 2383 consecutive patients with acute diarrhea. They provided stool samples for performing cultures. Patients with positive cultures and an equal number of matched controls with negative cultures underwent fecal occult blood test and calprotectin and lactoferrin assays. RESULTS: Calprotectin, lactoferrin, and fecal occult blood tests demonstrated sensitivity and specificity of 83% and 87%, 78% and 54%, and 38% and 85%, respectively, for diagnosing acute bacterial diarrhea. CONCLUSIONS: Calprotectin showed high correlation with bacteriologically positive infectious diarrhea compared with lactoferrin and fecal occult blood test. It may potentially revolutionize management algorithm for patients with acute diarrhea. As a screening test, calprotectin can generate results within hours to support presumptive diagnosis of infectious diarrhea, which can decide suitability of stool samples for culture.

PPARgamma is involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells.

PURPOSE: Mesalazine has been identified as a candidate chemopreventive agent in colon cancer prophylaxis because of its pro-apoptotic and anti-proliferative effects. However, the precise mechanisms of action are not entirely understood. The aim of our study was to investigate the involvement of peroxisome proliferator-activated receptor gamma (PPARgamma) in mesalazine's anticarcinogenic actions in colorectal cancer cells. EXPERIMENTAL DESIGN: The effects of mesalazine on cell cycle distribution, cell count, proliferation and caspase-mediated apoptosis were examined in Caco-2, HT-29 and HCT-116 cells used as wild-type, dominant-negative PPARgamma mutant and empty vector cultures. We focused on caspase-3 activity, cleavage of poly(ADP-ribose) polymerase (PARP), caspase-8 and caspase-9, as well as on expression of survivin, X-linked inhibitor of apoptosis (Xiap), phosphatase and tensin homolog deleted from chromosome ten (PTEN) and c-Myc. Techniques employed included transfection assays, immunoblotting, flow cytometry analysis, colorimetric and fluorometric assays. RESULTS: Mesalazine caused a time- and dose-dependent decrease in both cell growth and proliferation. Growth inhibition was accompanied by a G1/G0 arrest, a significant increase in PTEN, caspase-3 activity, cleavage of PARP and caspase-8, whereas the expressions of Xiap, survivin and c-Myc were decreased simultaneously. Cleavage of caspase-9 was not observed. Moreover, PPARgamma expression and activity were elevated. The growth-inhibitory effect of mesalazine was partially reduced in dominant-negative PPARgamma mutant cells, whereas the expression of c-Myc was not affected. Mesalazine-mediated increased caspase-3 activity, the expression of PTEN, cleavage of PARP and caspase-8 as well as reduced levels of survivin and Xiap were completely abolished in the PPARgamma mutant cell lines. CONCLUSION: This study clearly demonstrates that mesalazine-mediated pro-apoptotic and anti-proliferative actions are regulated via PPARgamma-dependent and -independent pathways in colonocytes.

Comparison of an established simple office-based immunological FOBT with fecal tumor pyruvate kinase type M2 (M2-PK) for colorectal cancer screening: prospective multicenter study.

OBJECTIVES: The immunological fecal occult blood test (IFOBT) has established itself as a more precise marker for colorectal cancer (CRC) screening than traditional guaiac-based FOBT. The simpler, cheaper, and more convenient newer office-based IFOBTs have been validated for diagnosing CRC. Dimeric isoenzyme of pyruvate kinase, M2-PK, expressed by tumor cells, has as well been proposed as a screening tool for CRC. This is the first study comparing fecal M2-PK as a screening biomarker for CRC against previously evaluated office-based IFOBT and colonoscopy. METHODS: Six hundred forty consecutive subjects (symptomatic, as well as for CRC screening) referred for colonoscopy for various indications across five centers in Germany provided the stool samples for performing M2-PK and an immunochemical FOB strip test. The IFOBT used was a rapid immunochromatographic assay for detection of fecal hemoglobin. For M2-PK, a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) was used. The M2-PK test needs 6 h, while the office-based test can be read in just 10 min and is five times cheaper. RESULTS: Office-based IFOBT had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR) of 64.5, 96.3, 72.0, 94.9, 17.5, and 0.4 for diagnosing colorectal neoplasia (CRN), while the above performance characteristics for M2-PK at a cutoff value of 4 U/mL were 72.4, 73.8, 29.0, 94.8, 2.8, and 0.8 respectively. CONCLUSIONS: This office-based IFOBT was found to have significantly higher specificity, PPV, and positive LR as compared with M2-PK. IFOBT proved to be a convenient, noncumbersome, quick, and cheap tool in patients with above-average risk for detection of CRN.

New introducer PEG gastropexy does not require prophylactic antibiotics: multicenter prospective randomized double-blind placebo-controlled study.

BACKGROUND: Peristomal infections are the most common complications of PEG, despite prophylactic antibiotics. The "introducer" PEG-placement technique avoids the sojourn of a PEG catheter through the oropharynx, and hence minimizes the chances of infectious complications. Despite the obvious potential advantage, this technique failed to gain popularity, mainly as a result of other associated risks and complications. Recently, a modified introducer endoscopic PEG-gastropexy technique was shown to be quite safe. The present study is the first study that evaluated the need of prophylactic antibiotics for "introducer" PEG. OBJECTIVE: To determine the incidence of peristomal wound infections during the immediate 7-day postprocedure follow-up. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTINGS: Multicenter; a university tertiary-care hospital and a private practice endoscopy clinic. PATIENTS: A total of 633 patients undergoing PEG were assessed for inclusion. Ninety-seven patients who had malignant stenotic oropharyngeal stricture were randomized: group I (49 patients) received prophylactic ceftriaxone, and group II (48 patients) received a placebo. Both groups were similar in patient characteristics. INTERVENTIONS: Introducer PEG was performed by using the Freka Pexact-15 CH/FR, with the gastric wall nonsurgically sutured to the anterior abdominal wall by use of an endoscope. MAIN OUTCOME MEASUREMENTS: The peristomal area was assessed daily for 7 days by using 2 different types of infection scores. RESULTS: Clinically significant wound reaction was observed in 1 patient in each group. Wound infection scores were marginally higher in the placebo group, but the differences in the values of infection scores between both the groups were not statistically significant during the 7-day post-PEG follow-up. LIMITATIONS: The introducer gastropexy kit is 5 times more expensive than the "pull" PEG. CONCLUSIONS: The new introducer PEG-gastropexy technique can be performed safely, without prophylactic antibiotics in patients potentially at high risk of peristomal infectious complications (those with advanced oropharyngeal malignancy) (ClinicalTrials.gov identifier NCT00375414).

Autologous blood as a submucosal fluid cushion for endoscopic mucosal therapies: results of an ex vivo study.

OBJECTIVE: Submucosal injection of fluid is used to elevate lesions in order to prevent perforation, which is the most calamitous complication during endoscopic resection therapies. There are several injection options when performing mucosal elevation (normal saline (NS), sodium hyaluronate (SH), etc.). Submucosal injection of fresh, autologous blood offers some advantages because of its specific properties: corpuscular components ensure prolonged elevation and procoagulatory constituents prevent post-interventional bleeding. The purpose of this study was to compare the ex vivo performance of autologous blood as a submucosal fluid cushion (SFC) with that of NS, SH and DW (dextrose water). MATERIAL AND METHODS: The proximal third of a resected porcine stomach was cut into squares. One millilitre NS, DW, SH and fresh porcine blood was injected into the submucosa. The height and duration of the submucosal injections were objectively measured during 1 h. Mucosal elevations were resected using an electro snare. RESULTS: The initial height and width of the mucosal elevations were comparable for SH and blood, and significantly higher compared with NS and DW. Mucosal elevation after injecting autologous blood persisted significantly longer compared with NS (p <0.05), but did not differ from hyaluronate. Histopathological examination of the resected specimen confirmed the appropriate submucosal injection of these substances. CONCLUSIONS: Submucosal injection of autologous blood with a standard endoscopic injection needle is possible and generates adequate mucosal elevation for the resection of high-quality specimens. This procedure could offer a "gratis" option for SFC as opposed to the expensive SH. Further clinical studies are needed to substantiate its use.

Liver biochemistry profile, significance and endoscopic management of biliary tract complications post orthotopic liver transplantation.

AIM: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy. METHODS: Patients who developed biliary complications were analysed in detail for the clinical information, laboratory tests, treatment offered, response to it, follow up and outcomes. The profile of liver enzymes was determined. The safety, efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed. RESULTS: 40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1 +/- 70.9 U/mL vs 168.5 +/- 34.2 U/L, P=0.007) and SAP > 2 times (345.1 +/- 59.1 U/L vs 152.7 +/- 21.4 U/L, P=0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%). Sustained success was achieved in 26 (81%) patients. CONCLUSION: Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early, non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.

Prospective multicenter evaluation of fecal tumor pyruvate kinase type M2 (M2-PK) as a screening biomarker for colorectal neoplasia.

Proliferating cells, particularly the tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed M2-PK. It's a direct target of several oncoproteins; the determination of fecal tumor pyruvate kinase type M2 (M2-PK) might be another promising tool for colorectal cancer (CRC) screening. In this study, we have evaluated fecal M2-PK as a screening biomarker for colorectal neoplasia. It was compared against fecal occult blood (FOB) and colonoscopy. Three hundred and seventeen consecutive subjects from 4 different centers were included. Stool specimens were collected before purgation, processed appropriately and were tested for FOB and quantitatively analyzed for M2-PK. Colonoscopies were performed by experienced endoscopists who were unaware of fecal assay results. At cutoff value of 4 U/ml, fecal M2-PK assay had a sensitivity, specificity, PPV and NPV of 81.1, 86.7, 71.1 and 61.9% respectively for diagnosing CRC whereas FOBT showed a sensitivity of 36.5%, specificity of 92.2%, PPV of 72.9% and NPV of 71.5% for CRC. Such low specificity of fecal M2-PK will lead to unacceptably high number of false positives if it is used for mass CRC screening, leading to unindicated colonoscopies with its associated inconveniences, risks and costs. CRC screening test must have high specificity; a high sensitivity is not as vital. To conclude, M2-PK was found to be a poor screening biomarker for CR neoplasia in a subject population at above average risk based on its prospective comparison with colonoscopy. These marginal performance characteristics do not permit its use as a screening tool for CR neoplasia in present clinical settings.