Purpose: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumor type. Experimental Design: Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted CDKN1B sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43). Results: Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of primary tumor (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%), and GIPR (74%). Conclusions: This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumors are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival. Clin Cancer Res; 22(1); 250–8. ©2015 AACR.

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BackgroundProstate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media.AimTo review the key evidence available for potential chemopreventive nutrients.MethodsThe methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”.ResultsRed meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer.ConclusionsFrom the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population.

Several pathogenic processes have been implicated in the development of abdominal ascites. Portal hypertension, most usually in the context of liver cirrhosis, can explain about 75% of the cases, whereas infective, inflammatory and infiltrative aetiologies can account for the rest. In this article, we discuss the consensus best practice as published by three professional bodies for the management of ascites, spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). The aim of this study was to compare available clinical guidelines and identify areas of agreement and conflict. We carried out a review of the guidance documentation published by three expert bodies including the British Society of Gastroenterology, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), as well as a wider literature search for ascites, SBP and HRS. Abdominal ultrasonography, diagnostic paracentesis and ascitic fluid cultures are recommended by all three guidelines, especially when there is strong clinical suspicion for infection. EASL and AASLD advocate the use of ascitic amylase and mycobacterial cultures/PCR when there is strong suspicion for tuberculosis and pancreatitis, respectively. Ascitic cytology can be useful when cancer is suspected and has a good diagnostic yield if performed correctly. EASL supports the use of urinary electrolytes for all patients; however, the British Society of Gastroenterology and AASLD only recommend their use for therapy monitoring. All three societies recommend cefotaxime as the antibiotic of choice for SBP and large-volume paracentesis for the management of ascites greater than 5 l in volume. For HRS, cautious diuresis, volume expansion with albumin and the use of vasoactive drugs are recommended. There appears to be good concordance between recommendations by the European, American and British guidelines for the management of ascites and the possible complications arising from it.

TAE/TACE are beneficial treatments for control of symptoms as well as tumor growth, with acceptable morbidity and mortality rates. No significant efficacy and survival differences were shown between TAE and TACE. Posttreatment CgA levels and the concurrent use of SSAs were independently associated with survival.

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Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence is increasing globally. NAFLD is a multifaceted disorder, and its spectrum includes steatosis to steatohepatitis, which may evolve to advanced fibrosis and cirrhosis. In addition, the presence of NAFLD is independently associated with a higher cardiometabolic risk and increased mortality rates. Considering that the vast majority of individuals with NAFLD are mainly asymptomatic, early diagnosis of non-alcoholic steatohepatitis (NASH) and accurate staging of fibrosis risk is crucial for better stratification, monitoring and targeted management of patients at risk. To date, liver biopsy remains the gold standard procedure for the diagnosis of NASH and staging of NAFLD. However, due to its invasive nature, research on non-invasive tests is rapidly increasing with significant advances having been achieved during the last decades in the diagnostic field. New promising non-invasive biomarkers and techniques have been developed, evaluated and assessed, including biochemical markers, imaging modalities and the most recent multi-omics approaches. Our article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, also highlighting the importance of accurate and validated diagnostic tools.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. There is growing evidence for a chemopreventive role of nutrition in the development of HCC in at risk populations. Bibliographical searches were performed in PubMed for the terms 'nutrition and hepatocellular carcinoma', 'nutrition and liver cancer', 'nutrition and hepatic cancer', 'diet and hepatocellular carcinoma', 'diet and liver cancer'. High dietary sugar intake should be discouraged in at risk populations. Coffee, polyphenols, vanadium, dietary fibre, fruits and vegetables show encouraging results in terms of chemoprevention. Red meat intake may be associated with increased risk of HCC. The evidence for fatty acids is inconclusive, but they might exert anti-cancer effects. Inconclusive results are available on vitamins, selenium probiotics and prebiotics. There is increasing evidence that diet may play an important role in the development of HCC, and may also have a chemopreventive role in at risk populations.