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Purpose: To evaluate the efficacy and safety of radiofrequency ablation (RFA) and new-generation microwave ablation (MWA) for the treatment of hepatocellular carcinoma (HCC)., Methods: The propensity score matching method was applied to patients with HCC treated with MWA (93 patients) or RFA (156 patients) at a single institution from January 2014 to April 2020. The local tumor progression (LTP), intrahepatic distant recurrence (IDR), and recurrence-free survival (RFS) of the two matched therapies were analyzed using the Kaplan-Meier method. Cox proportional hazard models were used to identify risk factors for LTP and RFS. The therapeutic effects and complications of the two treatments were also compared., Results: The LTP, IDR, and RFS of MWA and RFA were equivalent (LTP: hazard ratio [HR] = 0.87; 95% confidence interval [95% CI] 0.36- 2.07; P = 0.746, IDR: HR = 1.03; 95% CI 0.61-1.73; P = 0.890, RFS: HR = 1.15; 95% CI 0.69-1.91; P = 0.566). Para-vessel lesions was the only risk factor for LTP, whereas age, previous treatment, Albumin-Bilirubin score, and tumor diameter were risk factors for RFS. On the other hand, the ablation time per nodule (6.79 ± 2.73 and 9.21 ± 4.90 min; P = 0.008) and number of sessions per nodule required to achieve technical success (1.16 ± 0.39 and 1.34 ± 0.57; P = 0.009) were significantly lower in MWA than in RFA. The major complication rate of MWA and RFA was also equivalent., Conclusion: MWA and RFA have similar therapeutic effects and safety, although MWA has advantages over RFA regarding efficacy, including shorter ablation time and fewer sessions required., (© 2021. The Author(s).)

Background: To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction., Materials and Methods: We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors' institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions., Results: There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10(th), 20(th), and 30(th) examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10(th) exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections., Conclusion: Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Objectives: The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT., Methods: In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence., Results: A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73-1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77-1.71)., Conclusions: CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.

Background: In Japan, sorafenib is now the first-line therapy for individuals with advanced hepatocellular carcinoma (HCC), but no other treatment is available for such patients. The aim of this study was to assess the efficacy and safety of combination therapy with systemic continuous intravenous infusion of 5-fluorouracil (5-FU) and subcutaneous peginterferon alfa-2a, which was used before sorafenib was introduced to Japan., Methods: Two hundred and twenty-three HCC patients, who were not amenable to curative surgery, percutaneous ablation, or transarterial chemoembolization (TACE), and for whom intraarterial chemotherapy was not indicated because of the presence of extrahepatic metastasis or stenosis of the common hepatic artery, received peginterferon alfa-2a (90 μg subcutaneously on days 1, 8, 15, and 22) and 5-FU (500 mg/day intravenously given continuously on days 1-5 and 8-12). We assessed their response to treatment and survival, and treatment safety., Results: The response rate was 9.4 % (including six patients with complete response) and the disease-control rate was 32.7 %. The median time to progression was 2.0 months. The overall median survival time was 6.5 months (Child-Pugh class A: 9.2 months vs. Child-Pugh class B: 2.8 months). In a multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status >0, Child-Pugh class B, and the presence of macroscopic vascular invasion were independent predictors of poor prognosis. The major grade 3-4 adverse events were leucopenia (13.9 %) and thrombocytopenia (5.8 %). No treatment-related deaths occurred., Conclusions: This combination therapy was well tolerated and showed promising efficacy. Further studies are needed to establish the usefulness of this treatment.

Background & Aims: It is not fully elucidated whether obesity enhances hepatocarcinogenesis in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between body weight and risk of hepatocarcinogenesis in chronic hepatitis C patients., Methods: We enrolled 1431 patients with chronic hepatitis C who visited our liver clinic between 1994 and 2004, excluding those with hepatocellular carcinoma (HCC) at their visit or with a previous history of HCC. They were divided into 4 groups according to body mass index (BMI): underweight (< or =18.5 kg/m(2), N = 112); normal (18.5 to less than 25 kg/m(2), N = 1023); overweight (25 to less than 30 kg/m(2), N = 265); and obese (>30 kg/m(2), N = 31). We assessed the impact of obesity on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis., Results: During the follow-up period (mean, 6.1 y), HCC developed in 340 patients, showing cumulative incidence rates of 10.5%, 19.7%, and 36.8% at 3, 5, and 10 years, respectively. The incidence differed significantly among the BMI groups (P = .007). Adjusting for other significant factors, overweight and obesity were shown to be an independent risk factor of HCC, with a hazard ratio of 1.86 (95% confidence interval, 1.09-3.16; P = .022) and 3.10 (95% confidence interval, 1.41-6.81; P = .005) as compared with the underweight patients., Conclusions: The risk of HCC in patients with chronic hepatitis C increases in proportion to BMI in a wide range of its values, from underweight to obese.

Background and Aim: Local ablation therapy has been shown to be effective for small hepatocellular carcinoma (HCC); however, HCC recurrence is very frequent even after apparently curative treatment. In particular, recurrent HCC may be more prone to subsequent recurrence, although quantitative data are lacking. The aim of this study was to evaluate the difference in the risk for subsequent recurrence, if any, between primary and recurrent cases., Methods: A retrospective analysis was conducted of 376 patients with HCC (uninodular and 100 ng/mL, treatment other than radiofrequency ablation, HCV antibody positivity, and tumor multinodularity also remained as significant predictors., Conclusion: Hepatocellular carcinoma at second or later recurrence is three times as prone to subsequent recurrence as is primary HCC, when compared with adjustment for other tumor and hepatic factors.

Background and Aim: Impaired health-related quality of life has been reported in patients with cirrhosis and chronic hepatitis. However, only limited data are available concerning the influence of hepatocellular carcinoma., Methods: Health-related quality of life was assessed in 97 patients with hepatocellular carcinoma who had been treated successfully with percutaneous ablation therapy, and 97 patients with chronic liver disease without hepatocellular carcinoma matched for age and sex, using the Japanese version of Short-Form 36. Raw scores were transformed using norm-based scoring. The relations with objective variables including status of hepatocellular carcinoma and laboratory data were analyzed., Results: Health-related quality of life was lower in both groups than in the general population. Patients with hepatocellular carcinoma and patients in the control group showed similar scores. By multivariate analysis, liver function, especially serum albumin, strongly predicted health-related quality of life, but status of hepatocellular carcinoma did not., Conclusions: Impaired health-related quality of life was not associated with the presence of hepatocellular carcinoma but dependent on the level of liver function, indicating the importance of preserving liver function in following up patients. Serum albumin level was a useful objective variable to assess health-related quality of life of patients with chronic liver disease.

Three tumor markers for hepatocellular carcinoma (HCC) are available in daily practice in Japan: alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). To elucidate the predictability of these tumor markers on HCC recurrence after curative ablation, we enrolled 416 consecutive patients with naïve HCC who had been treated by percutaneous ablation at our department from July 1997 to December 2002. Tumor marker levels were determined immediately before and 2 months after the treatment. Complete ablation was defined on CT findings as nonenhancement in the entire lesion with a safety margin. Tumor recurrence was also defined as newly developed lesions on CT that showed hyperattenuation in the arterial phase with washout in the late phase. We assessed the predictability of recurrence via tumor markers in multivariate analysis, using proportional hazard regression after adjusting for other significant factors in univariate analysis. Until the end of follow-up, tumor recurrence was identified in 277 patients. Univariate analysis revealed the following factors to be significant for recurrence: platelet count; size and number of tumors; AFP, AFP-L3, and DCP preablation; and AFP and AFP-L3 postablation. Multivariate analysis indicated that AFP >100 ng/mL and AFP-L3 >15%, both pre- and postablation, were significant predictors. The positivity of AFP and AFP-L3 preablation that turned negative postablation was not significant. In conclusion, tumor markers pre- and post-ablation were significant predictors for HCC recurrence and can complement imaging modalities in the evaluation of treatment efficacy.

The dropout from the waiting list for liver transplantation among patients with hepatocellular carcinoma (HCC) is reportedly as high as 12% to 40% per year, mostly due to tumor progression. Considering the scarcity of donor organs, it would be beneficial if we could retain them within the Milan criteria with a bridging therapy. We retrospectively analyzed the prognosis of 288 HCC patients with relatively preserved liver function we treated with ablation therapy between 1997 and 2001, concentrating on whether they subsequently remained in the criteria, and analyzed the risk factors of dropout with Cox proportional hazards model. During a median follow-up period of 39 months (range, 1-86 months), 33 (11%) died without tumor progression, while 85 (30%) dropped out due to tumor progression. The overall dropout rate was 9.0% and 32.8% at 1 and 3 years, respectively, and that due to tumor progression was 6.2% and 23.0%. Cox regression analysis indicated that a high serum level of alpha-fetoprotein or des-gamma-carboxy prothrombin, and a tumor size exceeding 3 cm in diameter affected the dropout due to tumor progression, while low albumin concentration was a risk factor of death independently of tumor progression. In conclusion, local ablation therapy for HCC was effective in containing the tumor progression within the Milan criteria in selected patients.

Orthotopic liver transplantation (OLT) is potentially curative for patients with early stage hepatocellular carcinoma (HCC). However, tumor progression before OLT remains a problem. Ninety-three patients were listed for transplantation with HCC or diagnosed with HCC following listing between March, 1997 and September, 2001. Modified TNM Stage was I/II in 82 patients and III in 11 patients. Seventy-one patients (76%) were transplanted with a median waiting time of 3.4 months, and 22 (24%) patients were delisted owing to tumor progression (14), noncompliance (5), and death from liver failure (3). Using a cox model competing risks approach, higher baseline alpha-fetoprotein (AFP) >or= 100 ng/mL was the only factor independently associated with a higher hazard rate of delisting owing to tumor progression (p = 0.00003), whereas four separate factors were independently associated with a lower hazard rate of transplantation: more recent listing year (1999-2001, p = 0.010), blood type O (p = 0.013), Stage I HCC (p = 0.029), and serum bilirubin < 4 mg/dL (p = 0.032). By logistic regression, AFP >/= 100 ng/mL was the only factor that significantly influenced the probability of delisting owing to tumor progression (p = 0.001). In conclusion, the initial AFP level may be useful along with tumor stage in defining an urgency score for liver transplant candidates with HCC.

Objectives: Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT observed in explanted livers in relation to CT findings., Methods: A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Explanted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections., Results: Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. Histologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas., Conclusions: Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body-like inflammatory reaction and fibrosis. Pathologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed.

Background: The benefits of hepatic transplantation (HT) compared with hepatic resection (HR) in treating hepatocellular carcinoma (HCC) in patients with cirrhosis are controversial. The aim of this study was to compare the results of these therapeutic options., Methods: The charts of all patients with cirrhosis who underwent HR or HT for HCC between 1997 and 2000 were analyzed., Results: The cohort included 44 patients who underwent HR compared with 65 with HT. All patients in the HR group had Child's A disease, in contrast to the HT group, which included 23% Child's A and 77% Child's B and C patients. Whereas all HT patients spent at least three nights in the intensive care unit, 41% of the HR group never required critical care. Perioperative mortality was 7% in both groups. Pathologic analysis revealed T1/T2 disease in 43% of the HR group compared with 75% of the HT group. After 36 months of follow-up, there was no significant difference in overall survival (57% vs. 66%) or disease-free survival (36% vs. 66%) between the two groups., Conclusions: With overall survival and disease-free survival as the main outcomes, the results of HR versus HT are comparable in Child's A patients with HCC. In this patient subset, HR not only is an effective form of therapy, but is also associated with quicker recovery.