Percutaneous Radiofrequency Ablation with or without Chemolipiodolization for Hepatocellular Carcinoma: A Propensity-Score-Matched Analysis.

Chemolipiodolization (CL) is less invasive than transarterial chemoembolization (TACE) for managing hepatocellular carcinoma (HCC) because it helps avoid embolization. However, the treatment outcomes of percutaneous radiofrequency ablation (PRFA) with or without CL for HCC remain unclear. Herein, we compared the prognostic factors for overall survival (OS) following PRFA with or without CL for HCC using propensity-score-matched analysis. A total of 221 patients with HCC treated with PRFA at Saga Central Hospital between April 2004 and October 2020, with or without CL, were enrolled. No significant difference was observed in OS between PRFA with and without CL cohorts (median survival time (MST): 4.5 vs. 5.4 years; p = 0.0806). To reduce the confounding effects of 12 variables, we performed propensity-score-matched analysis to match patients treated with PRFA with or without CL. No significant difference was observed in OS between PRFA with and without CL cohorts (MST: 4.0 vs. 3.6 years; p = 0.5474). After stratification according to tumor size, no significant difference was observed in OS for patients with tumor size ≥20 mm between PRFA with and without CL cohorts (MST: 3.5 vs. 3.4 years; p = 0.8236). PRFA with CL was not a significant prognostic factor in both univariate and multivariate analyses (p = 0.5477 and 0.9600, respectively). Our findings suggest that PRFA with CL does not demonstrate more favorable prognosis than PRFA without CL for HCC, regardless of tumor size.

Hepatic Arterial Infusion Chemotherapy with Cisplatin versus Sorafenib for Intrahepatic Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled 331 patients with intrahepatic advanced HCC who received HAIC with cisplatin (n = 88) or sorafenib (n = 243) between June 2006 and March 2020. No significant difference was observed in OS between HAIC with cisplatin and sorafenib cohorts (median survival time [MST]: 14.0 vs. 12.3 months; p = 0.0721). To reduce confounding effects, 166 patients were selected using propensity score-matched analysis (n = 83 for each treatment). HAIC with cisplatin significantly prolonged OS compared with sorafenib (MST: 15.6 vs. 11.0 months; p = 0.0157). Following stratification according to the Child-Pugh classification, for patients with class A (MST: 24.0 vs. 15.0 months; p = 0.0145), HAIC with cisplatin rather than sorafenib significantly prolonged OS. Our findings suggest that HAIC with cisplatin demonstrates longer prognostic effects than sorafenib in intrahepatic advanced HCC.

Transarterial chemoembolization as salvage therapy after unsuccessful hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.

The prognosis for advanced hepatocellular carcinoma (HCC) remains unsatisfactory. Transarterial chemoembolization (TACE) and/or hepatic arterial infusion chemotherapy (HAIC) have been reported to be useful options. However, there are few reports of salvage therapies for patients without a curative response to initial chemotherapy. The aim of this study was to elucidate the efficacy of additional TACE as salvage therapy in cases of advanced HCC which failed to respond to HAIC. Of 43 patients with advanced HCC who did not show a complete response (CR) to HAIC, 12 were treated with additional TACE as salvage therapy (Group A). The rest were enrolled as disease control subjects (Group B). Response rates and prognosis were compared. For HAIC, cisplatin (10 mg/body on days 1-5) was administered. Subsequent treatment was the infusion of 5-fluorouracil (250 mg/body on days 1-5), which was scheduled for 4 serial courses. For TACE, carboplatin (150 mg/body) or epirubicin (30 mg/body) was administered mixed with 3 ml of ethiodized oil every 4 weeks. A CR or PR, ST and PD were observed in 6, 3, and 3 patients in Group A and 13, 18 and 0 patients in Group B, respectively. The difference in response between the two groups was significant (P=0.0074). The 1-, 2- and 3-year survival rates were 83.3, 75.0 and 44.4% in Group A and 83.9, 41.5 and 11.3% in Group B, respectively. Patients in Group A had a better prognosis than did those in Group B (P=0.018). Median survival was 31.9 months (5.8-41.1) in Group A and 16.2 months (3.3-53.2) in Group B. Consequently, TACE as salvage therapy after HAIC may improve the prognosis for patients with advanced HCC.

[A case of chronic hepatitis C virus-related advanced hepatocelluar carcinoma surviving more than 8 years].

A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis.

Clinical features of hepatitis C virus-related hepatocellular carcinoma and their association with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II.

PURPOSE: We investigated the differences in clinical features between alpha-fetoprotein (AFP)-predominant hepatocellular carcinoma (HCC) and protein induced by vitamin K absence or antagonist-II (PIVKA-II)-predominant HCC, especially regarding host factors thought to contribute to hepatocarcinogenesis in chronic hepatitis C virus (HCV) infection. METHODS: HCV-related HCC patients (n=306) were divided into four groups according to median AFP (48.1 ng/ml) and PIVKA-II (60 mAU/ml). Host factors, tumor factors, survival, and risk factors affecting survival were compared. RESULTS: Aspartate aminotransferase (AST; IU/L), alanine aminotransferase (ALT; IU/L), and platelet count (x 10(4)/ml) were, respectively, 81, 67, and 8.2 in AFP-predominant HCC (group A; n=66) vs. 50, 42, and 11.4 in PIVKA-II-predominant HCC (group P; n=52). Tumor sizes (mm) in groups A and P were 20 and 37, respectively. Significant differences were evident. Survival was identical between the two groups. Factors affecting survival were total bilirubin, portal tumor thrombus and number of nodule in group A, and albumin and tumor distribution in group P. CONCLUSIONS: PIVKA-II-predominant HCC had a milder hepatitis and a better-preserved platelet count compared with AFP-predominant HCC. Considering the strong relation between hepatocarcinogenesis and hepatic inflammation with chronic HCV infection, these differences indicate that hepatocarcinogenic mechanisms in PIVKA-II-predominant HCC may differ from those in AFP-predominant HCC.

Atypical manifestations of pancreatitis with autoimmune phenomenon in an adolescent female.

We report a case of an adolescent girl with atypical manifestations of pancreatitis with autoimmune phenomenon presenting with epigastralgia and back pain. While no abnormalities were detected on computed tomography and magnetic resonance imaging, apart from the absence of peripancreatic spread, laboratory and serological findings, such as hypergammaglobulinemia, a high titer of immunoglobulin G, a high titer of immunoglobulin G4, slight positivity for antinuclear antibodies, and positivity for autoantibodies to lactoferrin, were suggestive of autoimmune pancreatitis (AIP). Magnetic resonance cholangiopancreatography imaging (MRCP) visualized only the main pancreatic duct (MPD) in the pancreas head region. Proteoclastic enzyme inhibitor treatment was ineffective but the patient responded well to oral prednisolone. The patient and her family did not consent to endoscopic retrograde pancreatography or biopsy/histopathological examination. The case could not be diagnosed as AIP due to lack of typical diagnostic criteria, and thus the final diagnosis was considered pancreatitis with autoimmune phenomenon. We considered that the MRCP finding of partly visible MPD was due to diffuse irregular narrowing of the MPD. This case suggests that while MRCP imaging of the MPD may be helpful in the diagnosis of pancreatitis with autoimmune phenomenon, a negative result does not preclude such diagnosis.

Partial spontaneous regression of hepatocellular carcinoma: a case with high concentrations of serum lens culinaris agglutinin-reactive alpha fetoprotein.

Spontaneous regression of hepatocellular carcinoma (HCC) is rare. There are few reports discussing spontaneous regression associated with serum lens culinaris agglutinin-reactive alpha fetoprotein (AFP-L3). We describe a case of HCC with a high level of AFP-L3, which showed a rapid increase in alpha fetoprotein (AFP) concentration after partial spontaneous regression, and which was then treated successfully. A 71-year-old woman suffering from chronic hepatitis C underwent surgical resection for HCC. Preoperative concentrations of AFP fluctuated; subsequent to a transient decrease, a rapid increase in AFP was observed. AFP-L3 concentration was extremely high. The resected tissue consisted of encapsulated moderately differentiated HCC, subcapsular coagulation necrosis, and chronic active hepatitis. The postoperative course was uneventful. At present, 24 months after diagnosis, no symptoms or signs of tumor recurrence or metastasis have been observed. Although the precise etiology of the spontaneous regression in this patient is not known, we speculate that spontaneous regression of tumor cells with high malignant potential may be related to arterial involvement and insufficient blood supply.

Interventional radiology for advanced hepatocellular carcinoma: comparison of hepatic artery infusion chemotherapy and transcatheter arterial lipiodol chemoembolization.

OBJECTIVE: The prognosis of advanced hepatocellular carcinoma remains poor. The aim of this study was to compare the efficacy of hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization for treatment of advanced tumor. SUBJECTS AND METHODS. Thirty-seven patients with hepatocellular carcinoma and unresectable tumors were enrolled. In the hepatic artery infusion chemotherapy group (n = 16), cisplatin (10 mg/person, on days 1-5) and subsequent 5-fluorouracil (250 mg/person, on days 1-5) were administered for four serial courses. In the transcatheter arterial Lipiodol chemoembolization group (n = 21), an emulsion of Epirubicin (20-30 mg/person) and Lipiodol was administered every 3-4 weeks. RESULTS: The tumor response rates (complete response plus partial response for all cases) of the hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization groups were 56.3% and 23.8%, respectively, showing the significantly higher rate in the former than in the latter group. The cumulative survival rates between the two groups were not significantly different; whereas in those patients whose tumors were classified as TNM stage IV or as having the maximal tumor size of greater than 5 cm, patients tended to have higher survival rates in the hepatic artery infusion chemotherapy group than in the transcatheter arterial Lipiodol chemoembolization group. Univariate analysis identified the serum aspartate aminotransferase value as solely significant. Patients' adverse reactions were successfully managed by treatment of symptoms. Adverse events, such as obstructions of the catheter or hepatic artery or infection around the catheter, rarely occurred. CONCLUSION: Hepatic artery infusion chemotherapy had a better antitumor effect than transcatheter arterial Lipiodol chemoembolization and may be a useful therapeutic option for more advanced hepatocellular carcinoma.

Diagnostic clues for recurrent hepatocellular carcinoma: comparison of tumour markers and imaging studies.

OBJECTIVE: To elucidate the usefulness of monitoring Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin detected with a revised kit (DCP-R) as clues to the diagnosis of recurrent hepatocellular carcinoma (HCC). METHODS: A total of 57 patients with HCC were enrolled in the study. They were classified into two groups: group A comprised 27 patients in whom the diagnostic clue to recurrent HCC appeared before November 1997; these patients were monitored by ultrasonography, computed tomography (CT), AFP and des-gamma-carboxy prothrombin detected with a conventional kit (DCP-C). Group B comprised 30 patients in whom the diagnostic clue to recurrent HCC was detected after November 1997; these patients were monitored by ultrasound, CT, AFP, AFP-L3 and DCP-R. RESULTS: In group A, 22 and five HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. In group B, 17 and 13 HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. The number of patients in whom tumour markers were the first clue to the diagnosis of recurrent HCC was significantly higher in group B than in group A. CONCLUSIONS: Periodic examination of AFP-L3 and DCP-R may be useful for the early detection of recurrent HCC.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with advanced HCCs. METHODS: Forty-eight HCC patients with PVTT were treated by HAIC via a subcutaneously implanted injection port. Of these, 14 had PVTT in the second portal branch and 34 patients had PVTT in the first portal branch or in the main portal trunk. One course of chemotherapy consisted of daily cisplatin (7 mg/m(2) for 1 hour on Days 1-5) followed by 5-fluorouracil (170 mg/m(2) for 5 hours on Days 1-5). Patients were scheduled to receive four serial courses of HAIC. Responders were defined as having either a complete response (CR) or partial response (PR) and nonresponders were defined as exhibiting stable disease or progressive disease. The prognosis after HAIC and factors related to survival were analyzed. RESULTS: Following HAIC, 4 and 19 patients exhibited a CR and PR, respectively (response rate = 48%). The 1, 2, 3, and 5-year cumulative survival rates of 48 patients treated with HAIC were 45%, 31%, 25%, and 11%, respectively. Median survival periods for 23 responders and 25 nonresponders were 31.6 (range, 8.3-76.9) months and 5.4 (1.9-29.0) months, respectively. Therapeutic effect (P < 0.001) and hepatic reserve capacity (P = 0.021) were identified as significant prognostic factors by univariate analysis. Multivariate analysis identified only therapeutic effect as being significantly related to survival. CONCLUSIONS: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful therapeutic option for patients with advanced HCC with PVTT. HCC patients with PVTT who respond to HAIC could certainly have survival benefits.

Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan.

OBJECTIVE: We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. METHODS: Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). RESULTS: There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.