Radiofrequency ablation for management of malignant biliary obstruction: a single-center experience and review of the literature.

BACKGROUND: Radiofrequency ablation (RFA) causes coagulative necrosis of tissue and may be beneficial prior to biliary stenting. We report our experience using RFA for malignant biliary obstruction and review the literature. METHODS: Retrospective analysis of all patients undergoing RFA for malignant biliary obstruction over the last two years. Success, complications and re-intervention following RFA were assessed. Controls were age, sex and disease matched who had stenting alone. RESULTS: 31 patients were included and 15 patients underwent biliary RFA prior to stenting (median age 78 years, 8 females). 14 patients had pancreatic cancer, 13 cholangiocarcinoma (6 hilar lesions) and 4 malignant disease invading the bile duct. Adverse events included acute pancreatitis (n = 2) and bacteremia in (n = 1). Median duration of intervention free survival was 220 days in the RFA group compared to 106.5 days in controls (hazard ratio 2.4, 95% CI 1.1 - 5.3, p = 0.025). Multivariable Cox proportional hazard analysis showed survival was associated with RFA (hazard ratio 2.55, 95% CI 1.09-5.96, p = 0.026) but not age, site or type of malignancy. CONCLUSION: Biliary RFA is a technically feasible with a low adverse event rate and is associated with increased survival. Multi-centre randomized controlled trials are required.

Cytokine gene polymorphisms, cytokine levels and the risk of colorectal neoplasia in a screened population of Northeast Scotland.

Cytokine gene polymorphisms modify expression and their circulating protein levels reflect inflammatory response. Chronic inflammation plays a key role in the pathogenesis of colorectal neoplasia (CRN) associated with inflammatory bowel disease, but it is not clear whether inflammation is a cause or an effect of tumours in sporadic CRN. We therefore investigated the association of cytokine gene polymorphisms and circulating cytokine levels on the risk of CRN in Northeast Scotland, which has a high incidence of CRN. We recruited two groups of patients from a screening colonoscopy cohort, either preprocedure or 3-24 months postprocedure. Participants with CRN were compared with participants with no evidence of CRN (controls). Blood-derived DNA was used to genotype polymorphisms in IL1B, IL1-RN, IL6, IL8, IL10, PTGS2 and TNFA genes. Circulating levels of high-sensitivity C-reactive protein and six cytokines [interleukin-1ß (IL-1ß), IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-α (TNF-α)] were measured. To examine the effect of CRN resection on marker levels, we used propensity score matching. A total of 884 patients were eligible for analysis, including 388 CRN cases and 496 controls. Cases were older (mean age 64 vs. 62 years, P<0.01) and more likely to be men (67 vs. 55%, P<0.001). Controls were more likely to be regular users of NSAID (P<0.0001). Compared with homozygous carriage of respective common alleles, proinflammatory CC genotypes of IL1B-31C>T [odds ratio (OR) (95% confidence interval (CI) 1.68 (1.03-2.73)] and PTGS2-765 C>G [OR (95% CI) 2.97 (1.05-8.46)] were each associated with an increased risk of CRN. Conversely, carriage of the A allele of IL8-251A>T was associated with a lower risk of CRN compared with the TT genotype [ORs (95% CI) 0.60 (0.41-0.86) for heterozygous, 0.88 (0.57-1.37) for homozygous, and 0.68 (0.48-0.95) for heterozygous and homozygous combined]. Compared with postprocedure cases, IL8, TNF-α and C-reactive protein levels were significantly higher in preprocedure cases, but IL4 and IL10 protein levels were significantly lower. Proinflammatory cytokine gene polymorphisms in IL1B-31 and PTGS2-765 increase the risk of developing CRN. Levels of proinflammatory IL8, TNF-α and C-reactive protein markers are significantly higher while CRN is in situ. Along with the NSAID findings, these data point to inflammation as an underlying pathogenetic mechanism in CRN.

MicroRNAs in gastrointestinal malignancy: a tool in cancer prevention?

Gastrointestinal malignancies are a major cause of morbidity and mortality worldwide. Most cases are diagnosed at an advanced stage and, as such, 5-year survival rates are poor. MicroRNAs (miRNAs) are short, noncoding RNAs that negatively regulate gene expression at a post-transcriptional level. It is now evident that miRNAs are essential for normal physiological functioning, and aberrant miRNA expression is a hallmark of human cancers, including gastrointestinal cancers. Initially seen as a very promising source of breakthroughs in cancer management, there has been little translation of miRNA science from the bench to the bedside. This review will summarize the role of miRNAs in the pathogenesis of gastrointestinal malignancies. Further, it will serve to highlight the potential role of miRNAs in cancer prevention: namely their use as biomarkers and as targets for chemoprevention.

Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia: a case-control and immunohistochemical study.

BACKGROUND: Prostate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence. RESULTS: No genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence. CONCLUSION: From these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia.