Kenichi Takayasu

Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey

Advances in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) have improved the prognosis for patients with HCC who undergo liver resection. The objective of this study was to evaluate prognostic predictors for patients with HCC who underwent liver resection in a Japanese nationwide data base.

Report of the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan.

In the 17th Nationwide Follow‐up Survey of Primary Liver Cancer in Japan, 18 213 individuals were newly registered as patients with primary liver cancer at 645 medical institutions over a period of 2 years (from 1 January 2002 to 31 December 2003). Of these patients, 94.2% had hepatocellular carcinoma (HCC) and 4.1% had intrahepatic cholangiocarcinoma (ICC). In addition, 24 705 follow‐up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients, and the cumulative survival rates of newly registered patients in the 12th to 17th follow‐up surveys conducted between 1992 and 2003 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The data obtained in this follow‐up survey should contribute to future research and medical practice for primary liver cancer.

Pathology of small hepatocellular carcinoma. A proposal for a new gross classification

Review of 61 surgically resected small hepatocellular carcinomas (HCC) less than or equal to 3 cm in diameter yielded a simple gross classification system of five types based on tumor shape, which is highly correlated with microscopic and clinical features, including prognosis. Type 1 (single nodular type) tumors (n = 13) are expansile, roughly spheric, and often encapsulated. In Type 2 tumors (single nodular type with extranodular growth) (n = 21), replacing growth is often seen in the area of extranodular growth. Type 3 tumors (contiguous multinodular type) (n = 19) consist of small nodules growing in contiguity, often with replacing growth at the periphery. Type 4 (poorly demarcated nodular type) is a rare tumor showing infiltrating growth at its border. The authors define early HCC (n = 5) as the presence of tumor without destruction of the underlying liver structure. The lesions experienced are tiny (≤1.2 cm) and well differentiated. Poorly differentiated histologic characteristics and elevated alpha fetoprotein are more common in Types 2 and 3 than in Type 1. Type 1 has the highest rates of positive serum hepatitis B surface antigen and liver cirrhosis; portal vein tumor thrombus (PT) and/or intrahepatic metastasis (IM) is rare (7.7%), and the effect of transcatheter arterial embolization (TAE) is remarkable. This contrasts with Type 2, which has a high rate of PT and/or IM (71.4%) and multiple local recurrences (40%), and with Type 3, which shows a poor response to TAE.

Comparison of the outcomes between an anatomical subsegmentectomy and a non-anatomical minor hepatectomy for single hepatocellular carcinomas based on a Japanese nationwide survey.

BACKGROUND Although a surgical resection is an important modality for the treatment of hepatocellular carcinoma (HCC), the impact of the operative method on both the patient survival and disease-free survival (DFS) still remains controversial. METHODS Using a nationwide Japanese database, 72,744 patients with HCC who underwent a curative liver resection between 1994 and 2001 were divided into two groups based on whether an anatomical subsegmentectomy (AS) or a non-anatomical minor hepatectomy (MH) was performed. A total of 5,781 patients with single HCCs were selected for the study and divided into 3 subgroups based on the size of the HCCs (less than 2 cm, 2 to 5 cm, and greater than 5 cm in diameter). An AS was performed for 2,267 patients while an MH was performed for 3,514 patients. RESULTS The overall DFS was significantly better after an AS (P = .0089). When the patients were stratified according to the size of the HCC, a better DFS was seen in the patients with HCC from 2 to 5 cm after an AS (P < .0005). Further stratification according to liver damage did not show any significant differences between an AS and an MH. CONCLUSION An AS is therefore recommended, especially when the size of HCC ranges from 2 to 5 cm.

Clinical Study of Eighty-six Cases of Idiopathic Portal Hypertension and Comparison With Cirrhosis With Splenomegaly

The clinical features of 86 cases of idiopathic portal hypertension, the equivalent of hepatoportal sclerosis in the United States and of noncirrhotic portal fibrosis in India, are presented. This disease is characterized by overt splenomegaly with pancytopenia, portal hypertension, and relatively mild abnormalities in liver function tests. Although differential diagnosis from liver cirrhosis is not always easy, liver histology, laparoscopy, portography, hepatic venography, and measurement of wedged hepatic vein pressure are useful in diagnosis. Prognosis is relatively benign if variceal bleeding is controlled or prevented, and the disease does not progress to cirrhosis. The etiology is still undetermined, but the liver pathology characterized by occlusive changes of the intrahepatic portal radicles, portal and periportal fibrosis, and irregularly distributed parenchymal atrophies suggests some sort of portal venopathy that causes decreased portal perfusion of peripheral liver parenchyma. These patients with idiopathic portal hypertension were compared with 63 cases of cirrhosis with splenomegaly and 80 cases of cirrhosis without splenomegaly. There was some similarity in hematologic findings between idiopathic portal hypertension and cirrhosis with splenomegaly, but the basic disease process seemed distinctly different. The cause of marked splenomegaly does not seem to be simply congestion, and remains an enigma.

Surgical resection vs. percutaneous ablation for hepatocellular carcinoma: a preliminary report of the Japanese nationwide survey.

BACKGROUND/AIMS The treatment of choice for HCC remains controversial. We evaluated the therapeutic impact of surgical resection, PEI, and RFA for HCC on outcomes. METHODS A database derived from a Japanese nationwide survey of 17,149 patients with HCC treated by resection, PEI, or RFA between 2000 and 2003 was used to identify 7185 patients with no more than 3 tumors (< or = 3 cm) and a liver function of Child-Pugh class A or B. The patients classified into either a resection (n=2857), RFA (n=3022), or PEI group (n=1306) and their long-term outcomes were compared. RESULTS The median follow-up period was 10.4 months. The 2-year time-to-recurrence rate was 35.5%, 55.4%, and 73.3% in the resection, RFA, and PEI groups, respectively, while the number of recurrences was 2410, 2368, and 862. Although the number of deaths was 55 (1.9%), 49 (1.6%), and 39 (3.0%), the overall survival rates were not different. In a multivariate analysis, surgical resection was a significant negative factor for recurrence as compared with RFA (relative risk, 0.62 [95% confidence interval, 0.54-0.71], P<0.0001) and PEI (0.45 [0.38-0.52], P<0.0001). CONCLUSIONS This preliminary report suggested that surgical resection may provide less time-to-recurrence rate than either RFA or PEI in patients with HCC.

Report of the 18th follow-up survey of primary liver cancer in Japan

The 19th Nationwide Follow‐up Survey of Primary Liver Cancer in Japan comprised 20 850 primary liver cancer patients newly registered at 482 medical institutions over a period of 2 years (from 1 January 2006 to 31 December 2007). Of these, 94.7% had hepatocellular carcinoma (HCC) and 4.4% had intrahepatic cholangiocarcinoma (ICC). In addition, follow‐up data were obtained regarding 34 752 patients who were registered in the previous survey. Epidemiological and clinicopathological factors, diagnosis, and treatment were examined in newly registered patients. Compared with the 18th follow‐up survey, the present follow‐up survey suggested an increase in the number of elderly and female patients, a reduction in the number of hepatitis B surface antigen‐ and anti‐hepatitis C virus antibody‐positive patients, and a reduction in tumor size at the time of clinical diagnosis. In terms of local ablation therapy, the number of patients receiving radiofrequency ablation therapy increased. The cumulative survival rates for newly registered patients between 1996 and 2007 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified according to background factors and treatments. The cumulative survival rates of newly registered patients between 1978 and 2007 were calculated after dividing individuals into groups according to registration date (1978–1987, 1988–1997, and 1998–2007). The data obtained from this follow‐up survey will contribute to the medical management of primary liver cancer and facilitate future research.

Evaluation of the prognosis for small hepatocellular carcinoma based on tumor volume doubling time. A preliminary report

The relationship of tumor volume doubling time to length of patient survival was investigated for 15 patients with small hepatocellular carcinoma smaller than 4.5 cm in diameter. The mean tumor volume doubling time of these 15 nodules was 102 ± 77 days (mean ± SD; range 41 to 305 days) before the initiation of a specific treatment for cancer. These doubling times tended to correlate with mitotic indexes of the tumors and the patients could be divided into two groups according to the therapeutic modalities used. Patients in Group A received systemic chemotherapy without response or nonspecific treatments for cancer. In this group, there was a positive correlation between tumor volume doubling time and survival length (r = 0.8812; P < 0.025). Patients in Group B either received hepatectomy after transarterial embolization or systemic chemotherapy or received hepatectomy alone. In this group, early death occurred in patients who had shorter tumor volume doubling times. Three surgically treated patients in Group B were evaluated as having survived for a significantly long period as assessed from their tumor volume doubling times. These results indicate that tumor volume doubling time is one of the determining factors of survival length in patients with hepatocellular carcinoma, and, therefore, can be used in the evaluation of therapeutic efficacy.

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma — a comparison of lipiodol-transcatheter arterial embolization with and without Adriamycin (first cooperative study)

SummaryA randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE+ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P<0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma.

Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version)

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha‐fetoprotein (AFP) and AFP‐L3 and des‐gamma‐carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally.