Hideyuki Matsushima

Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment

The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF-FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin-fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification.

Novel Liver Visualization and Surgical Simulation System

BackgroundSuccessful liver surgery requires an understanding of the patient’s particular liver characteristics, including shape and vessel distribution. In clinical medicine, there is a high demand for surgical assistance systems to assess individual patients. Our aims in this study were to segment the liver based on computed tomography volume data and to develop surgical plans for individual patients.MethodsThe hepatic vessels were semi-automatically extracted from the segmented liver images, and the 3D shape of the liver and extracted vessel distribution were visualized using a surgical simulation system.ResultsThe 3D visualization of the liver allowed easy recognition of vessel and tumor location and selection of these structures with the 3D pointing device. The surgeon’s prior knowledge and clinical experience were integrated into the visualization system to create a practical virtual surgery, leading to improved functionality and accuracy of information recognition in the surgical simulation system.ConclusionsThe 3D visualization demonstrated details of individual liver structure, resulting in better understanding and practical surgical simulation.

Objective and Quantitative Assessment of Postoperative Pain in Digestive Surgery

Background: Pain is associated with subjective factors, making it difficult to assess. The PainVision™ system has been developed to quantitatively assess pain and compare postoperative pain intensity. We investigated the utility of PainVision in assessing postoperative pain in digestive surgery patients.

Phase I Study of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma

ABSTRACT Objectives: We conducted a phase I study of sorafenib and intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable hepatocellular carcinoma. Methods: Sorafenib was administered continuously, whereas cisplatin was administered once every 3 weeks. We estimated the safety and efficacy. Results: Fifteen patients were enrolled into this study. The dose-limiting toxicities occurred at sorafenib 800 mg and cisplatin 20 mg/m2. The recommended dose was at sorafenib 400 mg and cisplatin 30 mg/m2. The disease control rate was 73.3%. Conclusions: This treatment is feasible for unresectable hepatocellular carcinoma. Further evaluation of the regimen in a randomized controlled trial is warranted.