A patient with pancreas divisum, recurrent acute pancreatitis, and homozygosity for the cystic fibrosis transmembrane regulator-associated protein 5T allele.

Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) have been reported to increase the risk of recurrent acute pancreatitis in patients with pancreas divisum. We assessed the CFTR gene in a young male patient with pancreas divisum and recurrent acute pancreatitis. Magnetic resonance cholangiopancreatography and computed tomography revealed that the patient had pancreas divisum, with an enlarged and tortuous pancreatic duct; he also had positive results from the cystic fibrosis sweat test. Genetic analysis did not identify any common CFTR mutations, but did show that he was homozygous for the 5T allele in intron 8 IVS8 5T-12TG (which affects splicing at intron 8). Endoscopic sphincterotomy and stenting of papilla minor was performed. The IVS8 5T-12TG variant has been associated with abnormal organ development, therefore it is possible that CFTR has an important role in the development of the pancreatic duct. We propose this patient has recurrent acute pancreatitis resulting from a developmental defect associated with a suboptimal CFTR function.

Effect of colic vein ligature in rats with loperamide-induced constipation.

INTRODUCTION: Medical treatment in chronic constipation is not always successful. Surgery is indicated in unresponsive selected severe cases. This study presents the distal venous colic ligation in rat as a novel surgical approach. MATERIALS AND METHODS: 16 rats (study group) were evaluated in 3 phases of 6 days each: A (normal conditions), B (loperamide-induced constipation), and C (colic vein legation) and compared with rats treated in phase C with PEG 4,000 (control group). Blood biochemical and physiological parameters, daily fecal water content (FWC), and histological analysis were performed in all study phases. RESULTS: No biochemical and physiological parameters changes were observed. FWC decreased in phase B and increased in phase C in both groups with a grow up to 2.3-fold in study group compared to control (P < 0.0001). Moreover, in study group, a high number of colonic goblet cells were detected (phase C versus phase B: P < 0.001) while no differences were registered in control. CONCLUSION: By ligature of the colic vein in constipated rats, an increase in FWC and goblet cells higher than in PEG treated rats was detected. The described surgical procedure appeared effective, simple, and safe; further studies in animal models, however, are necessary to assess its clinical applicability.

Long term effects of gluten-free diet in non-celiac wheat sensitivity.

BACKGROUND & AIMS: Information about the clinical outcome of patients with non-celiac wheat sensitivity (NCWS) treated with gluten-free diet (GFD) derive from studies assessing the symptom response in the first few weeks of treatment. We aimed to evaluate the clinical response to the GFD and the quality of life (QoL) of NCWS patients in the long term. METHODS: Forty-four NCWS (diagnosed according to the Salerno criteria) participated in the study. Participants rated their symptoms according to a 0-10 scale patients and filled in a QoL questionnaire (CDQ) before the beginning of the GFD and during a follow-up evaluation performed after at least one year. To assess the reliability of the questionnaire we also included a control group of 43 matched patients with celiac disease (CD). RESULTS: Upon diagnosis, NCWS patients had a high prevalence of intestinal and extraintestinal symptoms. Also, most symptoms were described as severe and the QoL questionnaire showed high scores. On follow-up, both prevalence and severity of the most common symptoms were significantly reduced. However, persistent intestinal and extraintestinal symptoms of mild severity were found in 65.9 and 72.7% of NCWS patients. In comparison, in the CD group, the prevalence was lower (32.6 and 23.2% respectively) and consistent with previous studies. The analyses of the determinant of QoL showed that, upon diagnosis, NCWS patients had higher scores in the CDQ "gastrointestinal symptoms" (p < 0.001), "emotional aspects" (p < 0.001) and "social problems" (p < 0.001) subclasses compared to CD patients. After the GFD, NCWS and CD patients shared similar scores in all of the subclasses. CONCLUSIONS: A significant proportion of NCWS patients still complains of intestinal and extraintestinal symptoms, even if significantly attenuated by the GFD, even years after the diagnosis. A comprehensive nutritional evaluation of these patients is required to further improve their symptoms and their QoL.

c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

Clinical and diagnostic aspects of gluten related disorders.

Gluten is one of the most abundant and widely distributed components of food in many areas. It can be included in wheat, barley, rye, and grains such as oats, barley, spelt, kamut, and triticale. Gluten-containing grains are widely consumed; in particular, wheat is one of the world's primary sources of food, providing up to 50% of the caloric intake in both industrialized and developing countries. Until two decades ago, celiac disease (CD) and other gluten-related disorders were believed to be exceedingly rare outside of Europe and were relatively ignored by health professionals and the global media. In recent years, however, the discovery of important diagnostic and pathogenic milestones led CD from obscurity to global prominence. In addition, interestingly, people feeding themselves with gluten-free products greatly outnumber patients affected by CD, fuelling a global consumption of gluten-free foods with approximately $2.5 billion in United States sales each year. The acknowledgment of other medical conditions related to gluten that has arisen as health problems, providing a wide spectrum of gluten-related disorders. In February 2011, a new nomenclature for gluten-related disorders was created at a consensus conference in London. In this review, we analyse innovations in the field of research that emerged after the creation of the new classification, with particular attention to the new European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for CD and the most recent research about non-celiac gluten sensitivity.

Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a mouse experimental colitis model, independent of the anti-inflammatory effect.

BACKGROUND: Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. METHODS: The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. RESULTS: Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. CONCLUSIONS: Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.