Efficacy Of A Combination Of Transarterial Chemoembolization And Radiation Therapty For Patients With Hepatochellular Carcinoma Ineligible For Resection Or Radiofrequency Ablation.

Purpose: The local control rate of trans-arterial chemoembolization (TACE) for the patients with hepatocellular carcinoma (HCC) was unsatisfactory compared to resection or radiofrequency ablation (RFA). To increase the local control rate for tumors, we performed radiation therapy followed by TACE in our institution. The purpose of this study was to evaluate the efficacy and toxicity of the TACE and radiotherapy combination in HCC patients ineligible for resection or RFA. Material and Methods: Between January 2017 and April 2020, 33 patients with HCC ineligible for resection or RFA were treated with a combination of TACE and radiation therapy. Eight patients were initial cases, and 25 were recurrent or residual cases. A total dose of 40-60 Gy in 5-20 fractions was delivered to the 50-90% isodose line. Results: The median follow-up period was 16 months (range, 6-47 months); the objective response rate was 66.7%; and the 1- and 2-year overall survival rates, 72.7% and 62.5%, respectively. The objective response rate for HCCs <5 em was 79.2%; the 1- and 2-year overall survival rates, 91.7% and 62.5%, respectively; median progression-free survival, 13.5 months (range, 3-47 months), and the 1- and 2-year local progression-free survival rates, 95.8% and 85.7%, respectively. There was one case each of grade 2 radiation esophagitis and ascites after three months of irradiation. Conclusion: The combination of TACE and radiation therapy shows good local control and acceptable toxicity, particularly in HCCs <5 cm and may be a good treatment option

切除およびラジオ波凝固療法が適応外と判断された肝細胞癌症例に対する経動脈的化学塞栓療法と放射線療法の併用療法の効果

Purpose: The local control rate of trans-arterial chemoembolization (TACE) for the patients with hepatocellular carcinoma (HCC) was unsatisfactory compared to resection or radiofrequency ablation (RFA). We performed radiation therapy after TACE to increase the control rate in our institution. The purpose of this study was to evaluate the efficacy and toxicity of the TACE and radiotherapy combination in HCC patients ineligible for resection or RFA. Material and Methods: Between January 2017 and April 2020, 33 patients with HCC ineligible for resection or RFA were treated with a combination of TACE and radiation therapy. Eight patients were initial cases, and 25 were recurrent or residual cases. A total dose of 40-60 Gy in 5-20 fractions was delivered to the 50-90% isodose line. Results: The median follow-up period was 16 months (range, 6-47 months); objective response rate, 66.7%; and the 1- and 2-year overall survival rates, 72.7% and 62.5%, respectively. The objective response rate of HCCs <5 cm was 79.2%; the 1- and 2-year overall survival rates, 91.7% and 62.5%, respectively; median progression-free survival, 13.5 months (range, 3-47 months), and the 1- and 2-year local progression-free survival rates, 95.8% and 85.7%, respectively. There was one case each of grade 2 radiation esophagitis and ascites after three months of irradiation. Conclusion: The combination of TACE and radiation therapy shows good local control and acceptable toxicity, particularly in HCCs <5 cm and may be a good treatment option.博士（医学）・甲第837号・令和4年3月15

Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing

Numerical model-based simulations provide important insights into ion channel gating when experimental limitations exist. Here, a novel strategy combining numerical simulations with patch clamp experiments was used to investigate the net positive charges in the putative transmembrane segment 4 (S4) of the atypical, positively-shifted voltage-dependence of polycystic kidney disease 2-like 1 (PKD2L1) channel. Charge-neutralising mutations (K452Q, K455Q and K461Q) in S4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (Popen)-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor. Numerical reconstruction of wild-type (WT) and mutant PKD2L1-mediated currents necessitated, besides their voltage-dependent gating parameters, a scaling factor that describes the voltage-dependence of maximal conductance, Gmax. Subsequent single-channel conductance (γ) measurements revealed that voltage-dependence of Gmax in WT can be explained by the inward-rectifying property of γ, which is greatly changed in PKD2L1 mutants. Homology modelling based on PKD2 and NaVAb structures suggest that such voltage dependence of Popen and γ in PKD2L1 could both reflect the charged state of the S4 domain. The present conjunctive experimental and theoretical approaches provide a framework to explore the undetermined mechanism(s) regulating TRP channels that possess non-classical voltage-dependent properties

Predictive Factors of Complete Response to Transarterial Chemoembolization in Intermediate Stage Hepatocellular Carcinoma beyond Up-To-7 Criteria

Aim: To clarify the prognosis and identify predictors for obtaining a complete response (CR) by transarterial chemoembolization (TACE) in intermediate stage HCC beyond up-to-7 criteria. Methods: Of the 120 patients with intermediate stage HCC who were treated by TACE as the initial treatment from February 2007 to January 2016, 72 finally matched the following inclusion criteria: beyond up-to-7 criteria; Child–Pugh score under 7; and no combined therapy within 4 weeks after the initial TACE. The CR rate and overall survival (OS) were evaluated. Logistic regression analysis was performed to identify predictors of CR. The deterioration of liver function after TACE was also evaluated. Results: The CR rate was 56.9%, and the overall median survival time (MST) was 37.7 months. The MST was 38.7 months in the CR group and 28.0 months in the non-CR group (p = 0.018). HCC within up-to-11 criteria was the only predictor of CR. The CR rate and MST were 70.7% and 37.7 months, respectively, in patients with HCC within up-to-11 criteria and 38.7% and 32.7 months, respectively, in the patients beyond up-to-11 criteria. Deterioration of the Child–Pugh score after the initial TACE and the 2nd TACE occurred in 24.2% and 12.0%, respectively, and deterioration of the modified albumin-bilirubin (mALBI) grade occurred in 17.6% and 7.4%, respectively. Conclusion: TACE can achieve high CR rates with prolonged overall survival for intermediate stage HCC beyond up-to-7 criteria. The predictor of CR was within up-to-11 criteria. Deterioration of liver function was not severe, but requires caution. Multidisciplinary approach as additional treatment after TACE is important

Quantitative Analysis of Signal Heterogeneity in the Hepatobiliary Phase of Pretreatment Gadoxetic Acid-Enhanced MRI as a Prognostic Imaging Biomarker in Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma

Background: In the era of local and systemic therapies for intermediate-stage hepatocellular carcinoma (HCC), personalized therapy has become available. The aim of our study was to evaluate the usefulness of quantitative analysis of pretreatment gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis following transarterial chemoembolization (TACE). Methods: This retrospective study included patients with treatment-naïve intermediate-stage HCC who underwent EOB-MRI before the initial TACE and were treated by initial TACE between February 2007 and January 2016. Signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantitatively evaluated by the coefficient of variation (CV). The cutoff CV value was determined using the Classification and Regression Tree algorithm. Results: A total of 64 patients were enrolled. In multivariate analysis, High CV (≥0.16) was significantly associated with poor prognosis (p = 0.038). In a subgroup analysis of patients within up-to-7 criteria, MST was significantly shorter in the High CV group than in the Low CV group (37.7 vs. 82.9 months, p = 0.024). In patients beyond up-to-7 criteria, MST was 18.0 and 38.3 months in the High CV and Low CV groups, respectively (p = 0.182). In both groups scanned at 1.5 T or 3.0 T, High CV was significantly associated with poor prognosis (p = 0.001 and 0.003, respectively). Conclusion: CV of the tumor in the HBP of EOB-MRI is a valuable prognostic factor of TACE