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The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.

Objectives: Toronto hepatocellular carcinoma risk index is developed to stratify cirrhotic patients according to 10-year hepatocellular carcinoma risk. We aimed to validate the performance of Toronto hepatocellular carcinoma risk index in a large Turkish cohort., Materials and Methods: We retrospectively reviewed the database of 1287 cirrhotic patients followed-up in a 10-year period (February 2008 to January 2018). All patients were stratified into three groups based on the Toronto hepatocellular carcinoma risk index score as follows: low-risk, < 120; intermediate risk, 120 to 240; and high risk, > 240. Area under the curve and optimal cutoff value of Toronto hepatocellular carcinoma risk index were obtained from receiver operator curve. To reveal the parameters related with hepatocellular carcinoma development, logistic regression analysis was conducted. The cumulative incidences of hepatocellular carcinoma were calculated using the Kaplan-Meier method, and the curves were compared using the log-rank test., Results: Out of 403 enrolled patients, 57 developed hepatocellular carcinoma. The median Toronto hepatocellular carcinoma risk index value was higher in hepatocellular carcinoma (+) group comparing to hepatocellular carcinoma (-) group [267 (70-366) vs. 224 (36-366), P < 0.001]. Out of 57 detected hepatocellular carcinomas, 45 (78.9%) were high risk, 11 (19.3%) were intermediate risk, and only one (1.8%) was low risk at the entry. The area under the curve of the Toronto hepatocellular carcinoma risk index to predict hepatocellular carcinoma was 0.750 (95% confidence interval, 0.683-0.817, P < 0.001). The optimal cutoff value of Toronto hepatocellular carcinoma risk index was 239.5, giving a sensitivity of 78.9% and specificity of 62.7%. As a result, Toronto hepatocellular carcinoma risk index remained to be the only significant parameter that has an affect on hepatocellular carcinoma development [adjusted-odds ratio: 1.016 (95% confidence interval, 1.007-1.024), P<0.001]., Conclusion: The present study validated the performance of Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients to predict hepatocellular carcinoma risk, which can be considered as a tool for personalized surveillance.

Background and Aims: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by tumors arising from endocrine glands with no specific genotype-phenotype correlation. Herein, we report the largest Turkish kindred with MEN1 inherited a scarce MEN1 mutation gene., Materials and Methods: Sixty-four year-old man, referred to our gastroenterology outpatient clinic for evaluation of pancreatic mass lesion, was diagnosed with MEN1-syndrome after endoscopic ultrasound guided sampling of the mass revealing pancreatic neuroendocrine tumor (pNET), and accompanying primary hyperparathyroidism (PHPT) and pituitary tumor. Genetic analysis by whole gene Sanger sequencing of MEN1 gene identified a frame-shift mutation in exon 10 (c.1680&#95;1683delTGAG). All the relatives of the index case were proposed for clinical and genetic evaluation for MEN1-syndrome., Results: Of the 25 relatives of the index case, 17 were diagnosed MEN1-syndrome. Eighteen members among all relatives consented to genetic analysis and 11 had the same mutation as the index case. All the mutation positive members had MEN1, while none of mutation negative subjects had any sign of MEN1-syndrome. The frequencies of PHPT, pNET and pituitary tumors in this kindred were 94.1% (16/17), 29.4% (5/17) and 29.4% (5/17) respectively., Conclusion: We report rare MEN1 gene mutation which was descibed in a single sporadic patient before. It inherited in at least three generations of a large family, which has proven strong dominant effect on MEN1 phenotype. Further researches may be conducted to clarify potential candidacy of this mutation, as a hotspot for MEN1 patients, especially in Turkish population.

Natural killer (NK) cells have antifibrotic effects. We have evaluated the influence of rat bone marrow-mesenchymal stem cell (BM-MSC) treatment on liver histology, biochemical liver function tests, systemic immunoregulatory state and NK cell distribution in liver and peripheral blood in rat model of common bile duct (CBD) ligation and compared the results with the control group. Rats were divided into three groups: (1) CBD ligated (CBDL) rats received phosphate-buffered saline (CBDL + PBS group) or (2) MSC (CBDL + MSC group) and sham-operated rats received MSC (healthy + MSC group). We found significantly decreased fibrosis scores with BM-MSC treatment in CBDL rats compared to the control (CBDL + PBS) group while no fibrosis developed in sham operated (healthy + MSC) group. BM-MSC treatment has decreased the inflammation as reflected by the significantly decreased T cell proliferation and inflammatory cytokine concentrations from splenocyte culture and liver tissue itself compared to CBDL + PBS. NK cells both in parenchyme and portal areas decreased significantly in liver and blood in CBDL + PBS compared to healthy + MSC while they were found to be increased in CBDL + MSC compared to CBDL + PBS rats. In conclusion, BM-MSCs may suppress hepatic fibrosis accompanied by expanded intrahepatic NK cells in CBDL rats. Thus, our animal study shows that MSC treatment holds great promise for treatment of patients with end-stage liver diseases through a possible mechanism by adopting the NK cell population and new studies investigating the role of NK cells and clinical fibrosis are warranted.Trial registration number: Marmara University Animal Care and Use Committee approval code: 73.2013.mar.

Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2016 American Federation for Medical Research.)

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors found in the gastrointestinal (GI) tract, with the stomach being the most common site. They represent a distinct group of GI tumors originating from the interstitial cells of Cajal and are characterized by gain-of-function mutations of KIT. KIT oncoprotein serves as both diagnostic and therapeutic targets. Prognosis is related to size, mitotic activity, and site of the tumor. Asymptomatic, small endoscopic ultrasonography (EUS)-suspected GISTs are increasingly encountered with the wide availability of endoscopic/endosonographic examination. The majority of small GISTs are biologically indolent, albeit possibly harboring c-KIT gene mutations. An ongoing controversy exists regarding the management and surveillance policy for small gastric GISTs. A number of reports on the management of GISTs have been published, not confidently addressing the issue of gastric GISTs of small size. This work provides an overview on the current state of management considerations, specifically focusing on small EUS-suspected gastric GISTs, which are increasingly encountered by clinicians.

Background & Aims: Preliminary evidence suggests that inhibition of dipeptidyl peptidase (DPP)-IV preserves pancreatic beta cell function in patients with type 2 diabetes (T2D). However, its effects on liver histology in nonalcoholic steatohepatitis (NASH), hepatic complication of diabetes, have not yet been adequately explored. The present open-label, single-arm observational pilot study investigated the effects of one year of treatment with a dipeptidyl peptidase-IV inhibitor, sitagliptin, on liver histology, body mass index (BMI), and laboratory parameters in NASH patients with T2D., Patients and Methods: Paired liver biopsies from 15 diabetic patients with NASH (7 males, 8 females; mean age: 49.7 +/- 8.1 years (range: 36-62)) before and after one year of therapy with sitagliptin 100 mg once daily were studied. Clinical and laboratory parameters were recorded., Results: Treatment with sitagliptin resulted in a significant decrease in ballooning (P = 0.014) and NASH scores (P = 0.04), while the reduction in the steatosis score was of borderline statistical significance (P = 0.054). These effects were accompanied by a significant reduction in body mass index, AST, and ALT levels., Conclusion: Our study suggests that sitagliptin ameliorates liver enzymes and hepatocyte ballooning in NASH patients with T2D and may have therapeutic implications.