Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer.

BACKGROUND: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. METHODS: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. RESULTS: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p < 0.001 for multiplex and p = 0.007 for ELISA). Further, while >5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. CONCLUSION: Circulating IL-6 levels do not correlate with cachexia (when defined by weight loss), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.

Hepatobiliary cancers, version 2.2014.

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma), gall bladder, and bile ducts (cholangiocarcinomas). Gallbladder cancer and cholangiocarcinomas are collectively known as biliary tract cancers. Gallbladder cancer is the most common and aggressive type of all the biliary tract cancers. Cholangiocarcinomas are diagnosed throughout the biliary tree and are typically classified as either intrahepatic or extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinomas are more common than intrahepatic cholangiocarcinomas. This manuscript focuses on the clinical management of patients with gallbladder cancer and cholangiocarcinomas (intrahepatic and extrahepatic).

Hepatic Stellate Cells and microRNAs in Pathogenesis of Liver Fibrosis.

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by either blocking translation or inducing degradation of target mRNA. miRNAs play essential roles in diverse biological and pathological processes, including development of hepatic fibrosis. Hepatic stellate cells (HSCs) play a central role in development of hepatic fibrosis and there are intricate regulatory effects of miRNAs on their activation, proliferation, collagen production, migration, and apoptosis. There are multiple differentially expressed miRNAs in activated HSCs, and in this review we aim to summarize current data on miRNAs that participate in the development of hepatic fibrosis. Based on this review, miRNAs may serve as biomarkers for diagnosis of liver disease, as well as markers of disease progression. Most importantly, dysregulated miRNAs may potentially be targeted by novel therapies to treat and reverse progression of hepatic fibrosis.

Pretransplant Locoregional Therapy for Hepatocellular Carcinoma: Evaluation of Explant Pathology and Overall Survival.

BACKGROUND AND OBJECTIVES: Liver transplant is an important treatment option for patients with hepatocellular carcinoma (HCC) within Milan criteria. We sought to determine the rate of complete tumor necrosis after bridging therapy. METHODS: The medical records of all 178 patients undergoing liver transplantation between January 1, 2008 and July 31, 2015 were reviewed. Response to therapy by imaging was based on mRECIST criteria (1). RESULTS: Sixty-three (35%) patients had HCC. Forty-three (68%) were treated with at least one bridging therapy and 14 (22%) were diagnosed incidentally. Eighteen (42%) underwent TACE and 25 (58%) underwent ablation. Twenty (80%) patients who underwent ablation and nine (60%) who underwent TACE had complete response based on imaging. Viable tumor was identified in explant pathology in 32 patients (74%). The presence or absence of viable tumor was not associated with overall survival. CONCLUSION: Rates of viable tumor based on pathologic analysis in the hepatic explant were high after bridging therapy, but not associated with worse outcome. We conclude that serial bridging to achieve complete pathologic tumor response is not needed prior to transplant for HCC, and presence of complete response by imaging is adequate. Further studies are needed to determine if cancer cells that appear viable are alive.

Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro.

BACKGROUND: The purpose of this study was to determine the effect of a novel epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, Erlotinib, on pancreatic cancer cell lines of varying differentiation in vitro. METHODS: Six pancreatic cancer cell lines (AsPc-1, CAPAN-1, HPAC, HPAF-II, Mia PaCa-2, PANC-1) were grown in the presence of 50 microM or 100 microM of Erlotinib or recombinant EGF. Cell proliferation was determined using the MTT assay over 72 hours. The EGF receptor gene and protein expression were determined by polymerase chain reaction and immunohistochemistry respectively. RESULTS: All cell lines demonstrated the presence of the EGF receptor gene and its gene product. Five of six cell lines showed significant growth inhibition at 72 hours compared with controls (P <0.05). The EGF augmentation increased proliferation of each cell line but this increase was only significant in AsPc-1. CONCLUSIONS: Inhibition of EGF receptor is a valid therapeutic strategy in pancreatic cancer.

Laparoscopic distal pancreatectomy with splenic conservation: an operation without increased morbidity.

OBJECTIVES: The advent of minimally invasive techniques was marked by a paradigm shift towards the use of laparoscopy for benign distal pancreatic masses. Herein we describe one center's experience with laparoscopic distal pancreatectomy. METHODS: A retrospective chart review was performed for all distal pancreatectomies completed laparoscopically from 1999 to 2009. Outcomes from those cases completed with a concurrent splenectomy were compared to the spleen-preserving procedures. RESULTS: Twenty-four patients underwent laparoscopic distal pancreatectomy. Seven had spleen-conserving operations. There was no difference in the mean estimated blood loss (316 versus 285 mL, P = .5) or operative time (179 versus 170 minutes, P = .9). The mean tumor size was not significantly different (3.1 versus 2.2 cm, P = .9). There was no difference in the average hospital stay (7.1 versus 7.0 days, P = .7). Complications in the spleen-preserving group included one iatrogenic colon injury, two pancreatic fistulas, and two cases of iatrogenic diabetes. In the splenectomy group, two developed respiratory failure, three acquired iatrogenic diabetes, and two suffered pancreatic fistulas (71% versus 41%, P = .4). CONCLUSIONS: The laparoscopic distal pancreatectomy is a safe operation with a low morbidity. Splenic conservation does not significantly increase the morbidity of the procedure.