Cisplatin or Doxorubicin Reduces Cell Viability via the PTPIVA3-JAK2-STAT3 Cascade in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) accounts for 80% of all liver cancers and is the 2nd leading cause of cancer-related death in Taiwan. Various factors, including rapid cell growth, a high recurrence rate and drug resistance, make HCC difficult to cure. Moreover, the survival rate of advanced HCC patients treated with systemic chemotherapy remains unsatisfactory. Hence, the identification of novel molecular targets and the underlying mechanisms of chemoresistance in HCC and the development more effective therapeutic regimens are desperately needed. Methods: An MTT assay was used to determine the cell viability after cisplatin or doxorubicin treatment. Western blotting, qRT‒PCR and immunohistochemistry were utilized to examine the protein tyrosine phosphatase IVA3 (PTP4A3) level and associated signaling pathways. ELISA was utilized to analyze the levels of the inflammatory cytokine IL-6 influenced by cisplatin, doxorubicin and PTP4A3 silencing. Results: In this study, we found that PTP4A3 in the cisplatin/doxorubicin-resistant microarray was closely associated with the overall and recurrence-free survival rates of HCC patients. Cisplatin or doxorubicin significantly reduced cell viability and decreased PTP4A3 expression in hepatoma cells. IL-6 secretion increased with cisplatin or doxorubicin treatment and after PTP4A3 silencing. Furthermore, PTP4A3 was highly expressed in tumor tissues versus adjacent normal tissues from HCC patients. In addition, we evaluated the IL-6-associated signaling pathway involving STAT3 and JAK2, and the levels of p-STAT3, p-JAK2, STAT3 and JAK2 were obviously reduced with cisplatin or doxorubicin treatment in HCC cells using Western blotting and were also decreased after silencing PTP4A3. Collectively, we suggest that cisplatin or doxorubicin decreases HCC cell viability via downregulation of PTP4A3 expression through the IL-6R-JAK2-STAT3 cascade. Discussion: Therefore, emerging evidence provides a deep understanding of the roles of PTP4A3 in HCC cisplatin/doxorubicin chemoresistance, which can be applied to develop early diagnosis strategies and reveal prognostic factors to establish novel targeted therapeutics to specifically treat HCC.

Parenchymal Sparing Anatomical Liver Resections With Full Laparoscopic Approach: Description of Technique and Short-term Results.

OBJECTIVE: The aim of this study was to describe laparoscopic anatomical parenchymal sparing liver resections for hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) and report the short-term outcomes. BACKGROUND: Anatomical resections (ARs) have better oncological outcomes compared to partial resections in patients with HCC, and some suggest should be performed also for CRLM as micrometastasis occurs through the intrahepatic structures. Furthermore, remnant liver ischemia after partial resections has been associated with worse oncological outcomes. Few experiences on laparoscopic anatomical resections have been reported and no data on limited AR exist. METHODS: We performed a retrospective analysis of 86 patients undergoing full laparoscopic anatomical parenchymal sparing resections with preoperative surgical simulation and standardized procedures. RESULTS: A total of 55 patients had HCC, whereas 31 had CRLM with a median of 1 lesion and a size of 30 mm. During preoperative three-dimensional (3D) simulation, a median resection volume of 120 mL was planned. Sixteen anatomical subsegmentectomies, 56 segmentectomies, and 14 sectionectomies were performed. Concordance between preoperative 3D simulation and intraoperative resection was 98.7%. Two patients were converted, and 7 patients experienced complications. Subsegmentectomies had comparable blood loss (166 mL, P = 0.59), but longer operative time (426 min, P = 0.01) than segmentectomies (blood loss 222 mL; operative time 355 min) and sectionectomies (blood loss 120 mL; operative time 295 min). R0 resection and margin width remained comparable among groups. CONCLUSIONS: A precise preoperative planning and a standardized surgical technique allow to pursue the oncological quality of AR enhancing the safety of the parenchyma sparing principle, reducing surgical stress through a laparoscopic approach.

A series of laparoscopic liver resections with or without HALS in patients with hepatic tumors.

BACKGROUND: Differences were compared between laparoscopic surgery with and without hand-assisted laparoscopic technique (HALS) in order to assess whether HALS is a safe and feasible alternative to laparotomy and to determine what factors contributed to successful laparoscopic liver surgery. METHOD: From a total of 416 liver resections, 45 patients with 46 hepatic tumors were chosen for laparoscopic liver resection with or without a hand-assisted technique. For each patient, her/his surgical duration, intraoperative blood loss, tumor size and location, hospital stay after surgery, mortality, and morbidity were recorded for analysis. RESULTS: The 45 surgical laparoscopic liver resections included 19 left lateral lobectomies, three hemihepatectomies, three segmentectomies, and 21 partial hepatectomies. A HALS was used more frequently in the right posterior group (14/16) than in the anterior group (6/29). There was no notable difference between these two groups in terms of tumor size, mean surgical time, blood loss during surgical procedure, hospital stay after surgery, and occurrence of complication. CONCLUSION: Surgical results between HALS and non-HALS usage were similar except for higher blood loss with HALS, higher use of HALS when liver cirrhosis was present, and less likelihood of using HALS when there was a superficial location of the tumor or lesion.

Application of laparoscopic techniques for resection of individual gastric submucosal tumors.

Large gastric submucosal tumors should be excised to prevent ischemic mucosal ulceration of the overlying surface and central necrosis of the neoplasm, which may in turn lead to massive hemorrhage. Large tumors near the esophagocardiac junction or on the posterior wall are usually resected by an open procedure. We describe 2 cases of upper gastrointestinal tract bleeding owing to huge submucosal tumors in the posterior gastric high body treated by laparoscopic resection of the gastric tumors. These 2 patients recovered smoothly without major or minor complications. We emphasize that design of specific strategies for individual tumors is essential for the successful laparoscopic resection of tumors adjacent to the esophagocardiac junction and large tumors on the posterior wall.