Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival

<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage. In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin).</p> <p>Methods</p> <p>We evaluated the expression of IGF2BP3 by immunohistochemistry using a tissue microarray of 127 pancreatic ductal adenocarcinomas with tumor grade 1, 2 and 3 according to WHO criteria, and the prognostic value of IGF2BP3 expression.</p> <p>Results</p> <p>IGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues. Nine (38%) patient samples of tumor grade 1 (n = 24) and 27 (44%) of tumor grade 2 (n = 61) showed expression of IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (grade 3, n = 42) with 26 (62%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (P = 0.024; RR 2.3, 95% CI 1.2-4.8).</p> <p>Conclusions</p> <p>Our data suggest that IGF2BP3 overexpression identifies a subset of pancreatic ductal adenocarcinomas with an extremely poor outcome and supports the rationale for developing therapies to target the IGF pathway in this cancer.</p

Management of Polycystic Liver Disease

Polycystic liver disease (PCLD) is characterized by multiple cysts throughout the liver. Patients may develop chronic intractable symptoms that may be debilitating. Others may develop medical complications that necessitate intervention. There is a variety of nonsurgical and surgical treatment options for symptomatic or complicated PCLD, which range from cyst aspiration and fenestration to liver transplantation. Studies have described variable efficacy and morbidity. Currently, there are no guidelines for the management of PCLD patients and the optimal intervention is controversial. This article reviews the pathogenesis, classification and spectrum of treatment options for PCLD

Surgical Management of Dyslipidemia: Clinical and Experimental Evidence

Coronary artery disease (CAD) is still a major cause of mortality in developed countries, and dyslipidemia is one of its major causes. In an attempt to reduce both mortality and morbidity from CAD, several dietary, pharmacological, and surgical approaches have been used to reduce plasma cholesterol levels. In this brief review, we summarize the evidence for cholesterol-lowering effects and safety of partial ileal bypass (PIB) procedure in both human and animal studies. The results of the Program on the Surgical Control of the Hyperlipidemias (POSCH), which involved a total of 838 subjects with myocardial infarction, are promising. A 5-year follow-up of this study revealed significant reductions of up to 27% in total cholesterol (TC) and up to 42% in low-density lipoprotein (LDL) cholesterol levels along with an increase of up to 8% in high-density lipoprotein (HDL) cholesterol levels as compared to controls. These changes were associated with other benefits such as increased HDL/TC and HDL/LDL ratios, and a significant decrease in apolipoprotein (apo) B100 and increase in apo AI levels. Similar results were also demonstrated by other studies. PIB surgery is one of the most effective methods for reduction of plasma cholesterol levels, particularly in patients with heterozygous familial hypercholesterolemia. This procedure is also applicable to treatment of sitosterolemia, a rare genetic disorder in which the absorption of plant sterols is abnormally high. Although no major complications of this method have been reported, more extensive studies are required to evaluate its long-term effects on renal and hepatic function. Similarly, long-term impact of this procedure on progression/regression of atherosclerotic lesions must be documented. Finally, indications for this procedure should be carefully considered, particularly in view of availability of other treatments of dyslipidemia

The use of sildenafil to treat portopulmonary hypertension prior to liver transplantation

Portopulmonary hypertension (PPH) is an infrequent, but well-recognized complication of liver cirrhosis. PPH in those with end-stage liver disease has a significant impact on per-operative and intra-operative mortality, with liver transplantation being contraindicated in those individuals with mean pulmonary artery pressure exceeding 50 mmHg. Vasodilatory therapy is the mainstay of pharmacotherapy for PPH, although the evidence of benefit is largely extrapolated from the pulmonary hypertension literature. We report the use of the phosphodiesterase inhibitor, sildenafil, in a patient with end stage liver disease and PPH, with a pulmonary artery pressure before transplantation of 75 mmHg, to reduce pulmonary artery pressure prior to a successful liver transplant