Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance

<p>Abstract</p> <p>Background</p> <p>Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>OCT1 (<it>SLC22A1</it>) and OCT3 (<it>SLC22A3</it>) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.</p> <p>Results</p> <p>Real time PCR showed a downregulation of <it>SLC22A1 </it>and <it>SLC22A3 </it>in HCC compared to TST (p ≤ 0.001). A low <it>SLC22A1 </it>expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, <it>SLC22A1 </it>was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low <it>SLC22A1 </it>expression (< median) showed a higher <it>SLC22A3 </it>expression compared to HCC with high <it>SLC22A1 </it>expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the <it>SLC22A3 </it>expression.</p> <p>In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.</p> <p>Conclusion</p> <p>The downregulation of OCT1 is associated with tumor progression and a worse patient survival.</p

Effect of bariatric surgery on fatty liver disease in obese patients: A prospective one year follow-up study

Background. Non-alcoholic fatty liver disease (NAFLD), often associated with obesity and metabolic syndrome, manifests itself as steatosis, hepatic fibrosis, cirrhosis, or even end-stage liver disease. NAFLD causes inflammation, insulin resistance and cardiovascular complications. The current study aimed to evaluate the beneficial effects of bariatric surgery on biochemical parameters of hepatic functions in obese patients by comparing them before and one-year after the surgery. Methods. A total of 72 morbidly obese patients underwent bariatric surgery between 2016 and 2018. The incidence of diabetes mellitus in this group was 29%, median body weight was 124.5 kg (109.0-140.0) and mean body mass index (BMI) was 44.38 +/- 6.770 kg/m(2). The used surgical procedures included gastric bypass, sleeve gastrectomy, laparoscopic gastric plication, and single anastomosis duodeno-ileal bypass-sleeve gastrectomy. Biochemical parameters including ALT/AST ratio (AAR), NAFLD fibrosis score (NFS), hepatic fibrosis index (FIB-4) and Fatty Liver Index (FLI) were evaluated in all patients at the time of surgery and one year after the intervention. Results. Significant improvement after the intervention was observed in 64 patients. A significant reduction in body weight (P<0.0001), waist circumference (P<0.0001), and body mass index (P<0.0001) were observed. NAFLD liver fibrosis index changed significantly (P<0.0001), suggesting a trend of improvement from advanced fibrosis towards stages 0-2. The FIB-4 fibrosis index indicated significant improvement (P=0.0136). Besides, a significant decline in hepatic steatosis (P<0.0001) was observed after bariatric surgery as compared to the pre-surgery fatty liver conditions. Conclusion. Among the strategies to overcome NAFLD-associated impediments, bariatric surgery can be considered effective in reducing obesity and metabolic co-morbidities.University of Ostrava in The Czech Republi

Achalasia with megaesophagus and tracheal compression in a young patient: A case report

Introduction: Achalasia is one of the most common causes of dysphagia. Typical symptoms include difficulties in controlling the swallowing process, regurgitation, weight loss, and chest pain. A megaesophagus rarely causes tracheal compression with consecutive acute dyspnea or similar respiratory symptoms. Presentation of case: A 23-year-old male patient presented with difficulties in swallowing, a consecutive massive weight loss over the past three years, and minor respiratory ailments. Further diagnostics revealed a megaesophagus caused by achalasia leading to a severe compression of the trachea. A laparoscopic Heller myotomy with anterior semi-fundoplication 180° according to Dor was performed. Discussion: Acute dyspnea and similar respiratory symptoms are rarely observed in patients with achalasia, especially in young patients. Early diagnosis and timely, proper treatment are the hallmarks of restoring esophageal and tracheobronchial function and of successful prevention of severe long-lasting complications of the disease. When not treated properly, the disease may have progressed rapidly, leading to distinct respiratory symptoms such as stridor and acute dyspnea Conclusion: This report emphasizes that physicians should be alert and consider airway obstruction and signs of dyspnea as severe and threatening symptoms in extensive cases of achalasia with megaesophagus. Early surgical treatment provides a therapeutic option to obviate the occurrence of acute respiratory distress and consecutive complications. In particular, difficulties in intubation prior to surgery must be considered