Satoshi Moriya

Hepatocellular Carcinoma: Concomitant Sorafenib Promotes Necrosis after Radiofrequency Ablation—Propensity Score Matching Analysis

PURPOSE To retrospectively compare radiofrequency ablation (RFA) combined with the multikinase inhibitor sorafenib (hereafter, sorafenib-RFA) and RFA alone in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Between January 2007 and December 2011, 16 patients (mean age, 72.8 years; age range 52-84 years; 10 men, six women) with HCC tumors less than 3 cm in diameter were included in the sorafenib-RFA group, and 136 patients (mean age, 72.1 years; age range, 51-86 years; 92 men, 44 women) with HCC tumors less than 3 cm in diameter were included in the RFA alone (control) group. Mean diameters of the greatest long-axis dimensions of HCC were 22.8 mm ± 4.6 (standard deviation) in the sorafenib-RFA group and 18.1 mm ± 4.4 in the control group. RFA was performed immediately after the 7-day administration of sorafenib. Propensity score matching analysis was used to adjust for potential biases. RESULTS Fifteen of the 16 patients in the sorafenib-RFA group and 30 of the 136 patients in the control group were selected during propensity score matching. No significant differences between the sorafenib-RFA group (n = 15) and the control group (n = 30) were observed with regard to age, sex, etiology, Child-Pugh class, tumor size, puncture number, needle size, location at the liver margin, or location adjacent to a main vessel. The respective mean diameters of the greatest long- and short-axis dimensions of the RFA-induced ablated area were 46.3 mm ± 10.3 and 33.0 mm ± 6.9 in the sorafenib-RFA group and 32.9 mm ± 7.6 and 25.6 mm ± 5.7 in the control group; both of these dimensions were significantly larger in the sorafenib-RFA group (both P < .001). CONCLUSION Sorafenib-RFA may be superior to standard RFA alone in the treatment of HCC tumors smaller than 3 cm in diameter.

Contrast-enhanced ultrasonography findings using a perflubutane-based contrast agent in patients with early hepatocellular carcinoma

OBJECTIVE We evaluated the contrast-enhanced ultrasonography (US) imaging features of early hepatocellular carcinomas (HCCs) and compared these findings with those obtained using contrast-enhanced computed tomography (CT). SUBJECTS AND METHODS Forty-three patients with 52 early HCCs with a mean maximal diameter of 15.6mm were enrolled in this retrospective study. After confirming the location of the target lesion using fusion imaging combining conventional US and hepatobiliary phase of contrast-enhanced magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid, we evaluated findings of contrast-enhanced US using a perflubutane-based contrast agent. The contrast-enhanced US detection rates for hyper-vascularity in early HCCs were compared with those obtained for contrast-enhanced CT. RESULTS Transient hypo-vascularity subsequent to iso-vascularity during arterial phase and iso-vascularity during portal and post-vascular phases were the predominant contrast-enhanced US findings seen for 25 (48.1%) of the 52 early HCCs. Nine (17.3%) showed iso-vascularity during all three phases, while 1 (1.9%) showed hypo-vascularity during all three phases. The remaining 17 (32.7%) showed partial or whole hyper-vascularity during arterial phase, iso-vascularity during portal phase, and iso- or hypo-vascularity during post-vascular phase. The detection rate for the hyper-vascularity of early HCCs using contrast-enhanced US (32.7%, 17/52) was significantly higher than that obtained using contrast-enhanced CT (21.2%, 11/52) (P<0.05 by McNemar test). CONCLUSION Hypo-vascularity, iso-vascularity, and hyper-vascularity were observed during the arterial phase of contrast-enhanced US in 50.0%, 17.3%, and 32.7% of the early HCCs, respectively. Contrast-enhanced US was more sensitive than contrast-enhanced CT for the detection of hyper-vascularity in early HCCs. Of note, early HCCs might not exhibit the early arterial enhancement that is generally considered to be a typical finding for HCCs.

Use of contrast-enhanced ultrasonography with a perflubutane-based contrast agent performed one day after transarterial chemoembolization for the early assessment of residual viable hepatocellular carcinoma

OBJECTIVE We evaluated the efficacy of contrast-enhanced ultrasonography (US), compared with contrast-enhanced computed tomography (CT), for early assessments after transarterial chemoembolization (TACE) for the treatment of hypervascular hepatocellular carcinoma (HCC) lesions. SUBJECTS AND METHODS Thirty-two patients with 59 HCC lesions who were scheduled to receive TACE were enrolled in this prospective study. TACE was performed by injecting a mixture of iodized oil and miriplatin hydrate, followed by a gelatin sponge. Digital subtraction angiography (DSA) and/or contrast-enhanced CT were performed 2-6 months after TACE and were used as the reference standard for residual HCC; the detection rates for residual viable HCC using contrast-enhanced US with a perflubutane-based contrast agent and a high mechanical index (MI) mode performed one day after TACE were also compared with those obtained using contrast-enhanced CT performed one month after TACE. The comparisons were made using the McNemar test. RESULTS Forty-seven (79.7%) of the 59 HCC lesions were diagnosed as having residual viability based on DSA and contrast-enhanced CT findings obtained 2-6 months after TACE. Eight (17.0%) of the 47 HCC lesions that were diagnosed as having residual viability using one-day contrast-enhanced US were not detected using one-month contrast-enhanced CT because of artifacts produced by the high attenuation of the iodized oil. The detection rate for residual HCC lesions using one-day contrast-enhanced US (95.7%, 45/47) was significantly higher than that using one-month contrast-enhanced CT (78.7%, 37/47) (P<0.05). CONCLUSION Contrast-enhanced US performed one day after TACE is more sensitive than contrast-enhanced CT performed one month after TACE for detecting residual viable HCC.

Radiofrequency ablation combined with transarterial chemoembolization for subcapsular hepatocellular carcinoma: a prospective cohort study.

OBJECTIVE This study evaluated the safety and efficacy of using radiofrequency ablation combined with transarterial chemoembolization to treat hepatocellular carcinoma in a subcapsular location, given the increased risk of complications when using radiofrequency ablation alone. MATERIALS AND METHODS From January 2000 to December 2011, 1213 patients with unresectable hepatocellular carcinoma (up to three nodules) were screened. Of these, 132 patients with 132 subcapsular nodules (mean size, 3.0 cm; range, 1.2-5.0 cm) were enrolled in the study. After transarterial chemoembolization, percutaneous radiofrequency ablation was performed under ultrasound or C-arm cone-beam computed tomography guidance, on the same day or within 3 days. Local recurrence and survival curves were obtained using the Kaplan-Meier method. RESULTS Technical success of treatment was achieved in 130 patients (98.5%). Major complications, including pleural effusion, secondary peritonitis, and liver abscess, occurred in 3 patients (2.3%); the incidence of complications was associated with the number of needle insertions (1-2 vs. 3-4, P=0.039, Fishers exact test). No patients developed permanent sequelae, tumor seeding, or tumor bleeding. The 3-year local recurrence rate was 9.7%. Local recurrence was associated with the pretreatment serum des-gamma-carboxy prothrombin level (≤200 mAU/mL vs. >200 mAU/mL, P=0.019, log-rank test). The 3-, 5-, and 7-year overall survival rates in treatment-naïve cases (n=82) were 79.3%, 60.6%, and 50.9%, respectively. CONCLUSION Combination therapy using radiofrequency ablation and transarterial chemoembolization was a safe and useful therapeutic option for patients with subcapsular hepatocellular carcinoma.

Duodenal stenting followed by systemic chemotherapy for patients with pancreatic cancer and gastric outlet obstruction

OBJECTIVES Endoscopic duodenal stenting has recently been proposed as a substitute for surgical gastrojejunostomy for the treatment of gastric outlet obstruction. We aimed to evaluate the efficacy and safety of duodenal stenting followed by systemic chemotherapy for patients with advanced pancreatic cancer with gastric outlet obstruction. METHODS This was a single-center, retrospective cohort study, conducted at an academic medical center, of 71 patients with advanced pancreatic cancer and gastric outlet obstruction (mean age: 67.6 years; range: 31-92 years) who underwent duodenal stenting with or without subsequent chemotherapy. Overall survival, duration of oral intake of foods, the rate of introduction of chemotherapy, progression-free survival, and adverse events were evaluated. RESULTS Stent placement was technically successful in 69 (97%) patients. Thirty-six (51%) patients were treated with chemotherapy: 17 with gemcitabine alone, 15 with S-1 alone, 3 with FOLFIRINOX, and 1 with paclitaxel. Median progression-free survival and overall survival after chemotherapy were 2.6 months (95% confidence interval: 1.3-3.9 months) and 4.7 months (95% confidence interval: 2.6-6.8 months), respectively. Cases of grade 3 anemia were frequently observed during chemotherapies following duodenal stenting (32%). Tumor stage, performance status, neutrophil-to-lymphocyte ratio, and introduction of chemotherapy were independent prognostic factors for survival (hazard ratios of 3.73, 2.21, 2.69, and 1.85 with p-values of <0.001, 0.010, <0.001, and 0.045, respectively). CONCLUSIONS The findings of this study suggest that endoscopic duodenal stenting is an advantageous treatment in advanced pancreatic cancer patients with gastric outlet obstruction regarding its safety and smooth conduction of subsequent chemotherapies.

Short-term efficacy of transarterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres for hepatocellular carcinoma: comparison with conventional transarterial chemoembolization.

PurposeThis study aimed to compare the short-term efficacy of transarterial chemoembolization (TACE) with epirubicin-loaded superabsorbent polymer embolics (SAP) and conventional TACE in TACE-naïve patients with unresectable hepatocellular carcinoma (HCC).MethodsFifty consecutive patients (mean age, 72.8 years; hepatitis C, 46%; BCLC-A or B, 52% or 48%) treated with TACE with SAP during 2013–2015 and 55 consecutive patients (mean age, 71.8 years; hepatitis C, 40%; BCLC-A or B, 51% or 49%) treated with conventional TACE during 2011–2013 were evaluated. Safety evaluations were based on CTCAE ver. 4.0. Short-term efficacies, i.e., at 1 month after TACE, were assessed using the European Association for the Study of the Liver criteria. Overall survival rates were calculated using the Kaplan–Meier method. Short-term response markers were analyzed by univariate and multivariate analyses.ResultsThere was no significant difference in the incidence of any grade of adverse events. The objective response rates were 50% and 62% in patients treated with TACE with SAP and with conventional TACE, respectively (P = 0.358). The overall survival rates were not significantly different (P = 0.810); the 1-year survival rates and the median survival time of the patients treated with TACE with SAP and with conventional TACE were 76% and 74%, and 18 months and 21 months, respectively. Overall survival was related to the short-term response. An alpha-fetoprotein level <1,000 ng/mL was a significant short-term response marker on multivariate analysis.ConclusionsFor TACE-naïve patients, TACE with SAP and conventional TACE had comparable safety and short-term efficacies.

Switch to miriplatin for multinodular hepatocellular carcinoma unresponsive to transarterial chemoembolization with epirubicin: a prospective study

Objective The aim of this prospective study was to evaluate the efficacy of transarterial chemoembolization using miriplatin, a platinum-based anticancer drug, as a retreatment regimen for hepatocellular carcinoma (HCC) unresponsive to chemoembolization using epirubicin. Methods Between April 2013 and December 2014, we enrolled 57 consecutive chamoembolization-naïve patients with unresectable HCC, and performed chemoembolization with epirubicin. Treatment effect, necrotizing rate of the target nodules, was evaluated at 1-3 months after treatment using contrast-enhanced CT or MRI. We subsequently included retreatment chemoembolization with miriplatin for patients whose treatment effect was <50% after chemoembolization with epirubicin. The treatment effect after chemoembolization with miriplatin and the liver function before and after chemoembolization were evaluated. Results Eighteen patients of the 57 showed a treatment effect <50% after chemoembolization with epirubicin, and were switched to chemoembolization with miriplatin. The treatment effect after chemoembolization with miriplatin was ≥50% in four (22%) patients. Four of the remaining 14 (78%) patients who had <50% necrosis exhibited deterioration of the liver function after chemoembolization with miriplatin. Univariate analysis indicated that an alpha-fetprotein-L3 level <10% and a serum albumin level ≥3.6 g/dl were predictive factors of therapeutic response after chemoembolization with miriplatin (P < 0.05). However, there was no predictive factor regarding the deterioration of liver function after chemoembolization with miriplatin. Conclusions In unresectable HCC patients who were unresponsive to chemoembolization with epirubicin, switching the chemotherapeutic regimen to a platinum-based anticancer drug in retreatment chemoembolization should be considered as a treatment option. Trial registration: UMIN 000015887.

Unexpected Side Effects of a High S-1 Dose: Subanalysis of a Phase III Trial Comparing Gemcitabine, S-1 and Combinatorial Treatments for Advanced Pancreatic Cancer

Objective: In this subanalysis of a phase III trial using three categorized doses of S-1, the influence of the actual doses on safety and efficacy was evaluated. Methods: We compared the efficacy and safety of the S-1 or gemcitabine plus S-1 combination (GS) arm between the top 10% group and the bottom 10% group according to the initial doses of S-1: ≥77.6 versus ≤65.9 mg/m2/day (n = 28 vs. 28) in the S-1 arm, and ≥65.1 versus ≤53.8 mg/m2/day (n = 27 vs. 28) in the GS arm. Results: Overall and progression-free survival were not significantly different between these two groups: hazard ratios of 0.818 and 0.761 with p values of 0.498 and 0.330 in the S-1 arm, and hazard ratios of 0.836 and 0.759 with p values of 0.557 and 0.323 in the GS arm, respectively. Incidences of grade 3-4 hematological toxicities were significantly higher in the top 10% group than in the bottom 10% group: 42.9 versus 14.3 and 85.2 versus 57.1%, with p values of 0.037 and 0.037 in the S-1 and the GS combination arm, respectively. Conclusions: Higher actual doses of S-1 were associated with a higher incidence of hematological toxicity even in the same dose setting.

Effects of IL-28B gene polymorphism on response to peginterferon plus ribavirin combination therapy for genotype 2 chronic hepatitis C

Interleukin (IL)‐28B gene polymorphism is closely linked with treatment response to peginterferon plus ribavirin combination therapy for hepatitis C virus genotype 1. However, few studies have reported its effects on therapy for genotype 2. We aimed to examine the effects of IL‐28B gene polymorphism on treatment response in hepatitis C virus genotype 2 patients.