RESUMO
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, representing the most common form of liver cancer. As HCC incidence and mortality continue to increase, there is a growing need for improved translational animal models to bridge the gap between basic HCC research and clinical practice to improve early detection and treatment strategies for this deadly disease. Recently the Oncopig cancer model-a novel transgenic swine model that recapitulates human cancer through Cre recombinase induced expression of KRAS G12D and TP53 R167H driver mutations-has been validated as a large animal translational model for human HCC. Due to the similar size, anatomy, physiology, immunology, genetics, and epigenetics between pigs and humans, the Oncopig has the potential to improve translation of novel diagnostic and therapeutic modalities into clinical practice. Recent studies have demonstrated the importance of tumor cells in shaping its surrounding microenvironment into one that is more proliferative, invasive, and metastatic; however, little is known about the impact of microenvironment signaling on HCC tumor biology and differential gene expression between HCC tumors and its tumor microenvironment (TME). In this study, transcriptional profiling was performed on Oncopig HCC xenograft tumors (n = 3) produced via subcutaneous injection of Oncopig HCC cells into severe combined immunodeficiency (SCID) mice. To differentiate between gene expression in the tumor and surrounding tumor microenvironment, RNA-seq reads originating from porcine (HCC tumor) and murine (microenvironment) cells were bioinformatically separated using Xenome. Principle component analysis (PCA) demonstrated clustering by group based on the expression of orthologous genes. Genes contributing to each principal component were extracted and subjected to functional analysis to identify alterations in pathway signaling between HCC cells and the microenvironment. Altered expression of genes associated with hepatic fibrosis deposition, immune response, and neo angiogenesis were observed. The results of this study provide insights into the interplay between HCC and microenvironment signaling in vivo, improving our understanding of the interplay between HCC tumor cells, the surrounding tumor microenvironment, and the impact on HCC development and progression.
RESUMO
PURPOSE: To quantify the pooled clinical outcomes of stent-graft transjugular intrahepatic portosystemic shunt (TIPS) creation for the management of gastric varices (GVs) through systematic review of the literature and meta-analysis. MATERIALS AND METHODS: A PubMed and Embase search was performed from 2003 to 2020. Search terms included: (transjugular intrahepatic portosystemic shunt OR TIPS) AND (gastric varices OR fundal varices OR gastroesophageal varices OR gastroesophageal varices) AND (hemorrhage OR rebleeding OR rebleeding OR survival). Inclusion criteria spanned: English language studies, publication in peer reviewed journals, sample size ≥ 10, reported clinical outcome data, exclusive treatment of GVs (no esophageal varices), exclusive use of stent-grafts for TIPS, no chemical obliteration of GVs. Outcomes included GV rebleeding rate, overall rebleeding rate, GV occlusion rate, hepatic encephalopathy (HE) incidence, and adverse event (AE) rate. RESULTS: Literature search yielded 936 articles. Of these, 5 (0.5%) retrospective observational cohort studies met inclusion criteria, spanning 209 patients (quinquagenarian men with viral or alcoholic liver disease) with GVs treated using TIPS with adjunctive coil embolization (47%). Clinical follow-up time ranged from 4.3 to 30.6 months. Outcomes included a pooled GV rebleeding rate of 15% (95% CI: 11%, 20%), total rebleeding rate of 21% (95% CI: 15%, 27%), GV occlusion rate of 33% (95% CI: 22%, 45%), HE incidence of 30% (95% CI: 24%, 36%), and AE incidence of 3% (95% CI: 1%, 8%). CONCLUSION: The incidence of GV rebleeding after stent-graft TIPS is high. The results suggest the need for additional measures to reduce recurrent hemorrhage incidence from GVs.
