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Iijima H, Kudo M, Kubo S, Kurosaki M, Sakamoto M, Shiina S, Tateishi R, Osamu N, Fukumoto T, Matsuyama Y, Murakami T, Takahashi A, Miyata H, Kokudo N. Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015). Hepatol Res 2023; 53:895-959. [PMID: 37574758 DOI: 10.1111/hepr.13953] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/01/2023] [Indexed: 08/15/2023]
Abstract
For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20 889 newly registered patients and 42 274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child-Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.
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Affiliation(s)
- Hiroko Iijima
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Masatoshi Kudo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Shoji Kubo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Masayuki Kurosaki
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michiie Sakamoto
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- School of Medicine, International University of Health and Welfare, Tokyo, Japan
| | - Shuichiro Shiina
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nakashima Osamu
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Takamichi Murakami
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Arata Takahashi
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Clinical Database, Tokyo, Japan
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Clinical Database, Tokyo, Japan
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Center for Global Health and Medicine, Tokyo, Japan
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Kudo M, Izumi N, Kokudo N, Sakamoto M, Shiina S, Takayama T, Tateishi R, Nakashima O, Murakami T, Matsuyama Y, Takahashi A, Miyata H, Kubo S. Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013). Hepatol Res 2022; 52:5-66. [PMID: 34050584 DOI: 10.1111/hepr.13675] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/12/2021] [Accepted: 05/15/2021] [Indexed: 12/15/2022]
Abstract
In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.
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Affiliation(s)
- Masatoshi Kudo
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Namiki Izumi
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Norihiro Kokudo
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Nakashima
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takamichi Murakami
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Arata Takahashi
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shoji Kubo
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Kudo M, Izumi N, Kokudo N, Sakamoto M, Shiina S, Takayama T, Tateishi R, Nakashima O, Murakami T, Matsuyama Y, Takahashi A, Miyata H, Kubo S. Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011). Hepatol Res 2021; 51:355-405. [PMID: 33382910 DOI: 10.1111/hepr.13612] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/01/2020] [Accepted: 12/13/2020] [Indexed: 12/11/2022]
Abstract
In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.
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Affiliation(s)
- Masatoshi Kudo
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Namiki Izumi
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Norihiro Kokudo
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Nakashima
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takamichi Murakami
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Arata Takahashi
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shoji Kubo
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Zhou J, Yan T, Bi X, Zhao H, Huang Z, Zhang Y, Li Y, Feng L, Wang J, Cai J. Evaluation of seven different staging systems for alpha-fetoprotein expression in hepatocellular carcinoma after hepatectomy. Tumour Biol 2013; 34:1061-70. [PMID: 23322323 DOI: 10.1007/s13277-013-0646-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2012] [Accepted: 01/02/2013] [Indexed: 01/11/2023] Open
Abstract
Alpha-fetoprotein (AFP) represents the most important biomarker for hepatocellular carcinoma (HCC). The aim of this study was to identify the optimal staging system to predict the survival of AFP-negative and AFP-positive patients. This study analyzed the data of 431 AFP-negative HCC patients who had previously undergone surgery and 471 AFP-positive HCC candidates. Kaplan-Meier (K-M) survival estimates were plotted, and the P values were assessed using log-rank tests. The Akaike information criterion (AIC) was calculated using the results of a Cox's regression to compare the overall assessment of the seven different staging systems. The AFP-positive group displayed characteristics of poor tumor biological behavior (tumor multiplicity [P = 0.032], low grade differentiation [P = 0.000] and carcinoma cell embolus [P = 0.031]), poor liver function (Child-Pugh B classification [P = 0.003], abnormal prothrombin time activity [P = 0.037] and moderate/severe cirrhosis [P = 0.000]) and increased operative difficulties (transfusion; P = 0.001). TNM7th staging showed the lowest AIC value (1,279.528) for the AFP-negative group, while the Barcelona Clinic Liver Cancer (BCLC) staging system revealed the lowest AIC value (1,991.233) for the AFP-positive group. In conclusion, among the seven favorable staging systems, BCLC staging was superior for the AFP-positive group, while the TNM7th was a more appropriate staging model for the AFP-negative group.
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Affiliation(s)
- Jianguo Zhou
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China
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Kawamura Y, Ikeda K, Hirakawa M, Yatsuji H, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma. Hepatol Res 2010; 40:1006-14. [PMID: 20887336 DOI: 10.1111/j.1872-034x.2010.00703.x] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM The aim of this study was to elucidate whether the histopathological characteristics of hepatocellular carcinoma (HCC) can be predicted from baseline dynamic computed tomography (CT) images. METHODS This retrospective study included 86 consecutive patients with HCC who underwent surgical resection between January 2000 and September 2008. The arterial- and portal-phase dynamic CT images obtained preoperatively were classified into four enhancement patterns: Type-1 and Type-2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively; Type-3, heterogeneous enhancement pattern with septum-like structure; and Type-4, heterogeneous enhancement pattern with irregular ring-like structures. We also evaluated the predictive factors for poorly-differentiated HCC, specific macroscopic type of HCC (simple nodular type with extranodular growth [SNEG] and confluent multinodular [CMN]) by univariate and multivariate analyses. RESULTS The percentages of poorly-differentiated HCC according to the enhancement pattern were three of 51 nodules (6%) of Type-1 and -2, three of 24 (13%) of Type-3, and eight of 11 (73%) of Type-4. The percentages of SNEG/CMN according to the enhancement pattern were 12 of 51 nodules (24%) of Type-1 and -2, 13 of 24 (54%) of Type-3, and five of 11 (45%) of Type-4. Multivariate analysis identified Type-4 pattern as a significant and independent predictor of poorly-differentiated HCC (P < 0.001) while Type-3 pattern was a significant predictor of SNEG/CMN (P = 0.017). CONCLUSION Heterogeneity of dynamic CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment.
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Umemura T, Ichijo T, Yoshizawa K, Tanaka E, Kiyosawa K. Epidemiology of hepatocellular carcinoma in Japan. J Gastroenterol 2009; 44 Suppl 19:102-7. [PMID: 19148802 DOI: 10.1007/s00535-008-2251-0] [Citation(s) in RCA: 151] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2008] [Accepted: 07/03/2008] [Indexed: 02/06/2023]
Abstract
Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), is ranked third in men and fifth in women as a cause of death from malignant neoplasms in Japan. The number of deaths and death rate of HCC began to increase sharply in 1975. These numbers peaked at 34,510 and 27.4/100,000, respectively, in 2004, but decreased to 33,662 annual deaths and a 26.7/100,000 death rate in 2006. Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are both major causes of HCC, HCV-related HCC represents 70% of all cases. The incidence of HCC without hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV) accounts for 8%-15% of HCC patients nationwide. Geographically, HCC is more frequent in western than eastern Japan, and death rates of HCC in each prefecture correlate with anti-HCV, but not HBsAg, prevalence. Interferon therapy for chronic hepatitis C reduces the risk of development of HCC, especially among patients with sustained virological response. Further research should focus on the mechanisms of carcinogenesis by HCV and HBV, development of more effective treatments, and establishment of early detection and preventative approaches. Better understanding of HCC unrelated to HCV and HBV, possibly caused by steatohepatitis and diabetes, should also be a major concern in future studies.
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Affiliation(s)
- Takeji Umemura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
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Hong CK, Yang JM, Kang BK, Kim JD, Kim YC, Chang UI, Yoo JY. A case of combined hepatocellular-cholangiocarcinoma with underlying schistosomiasis. Korean J Intern Med 2007; 22:283-6. [PMID: 18309689 PMCID: PMC2687661 DOI: 10.3904/kjim.2007.22.4.283] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. We report here on a case with collision tumor, which apparently was the coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma underlying schistosomiasis. A 39-year-old-Philippine female was transferred to our hospital for evaluation of a liver mass that was found on ultrasonography at a local hospital. HBsAg and Anti-HCV were negative and serum alpha-fetoprotein (AFP) level was normal. The tumor mass was histologically diagnosed as adenocarcinoma by sono-guided biopsy before the operation. Partial lobectomy was performed and we histologically identified the concurrent occurrence of hepatocellular carcinoma and cholangiocarcinoma, (a "collision type carcinoma").
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Affiliation(s)
- Chang Kyun Hong
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Mo Yang
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Bong Koo Kang
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Dong Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Young Chul Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - U-Im Chang
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Young Yoo
- Department of Pathology, The Catholic University of Korea College of Medicine, Seoul, Korea
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Abstract
Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. Although the number of deaths and death rates from HCC increased until 2002 in Japan, annual deaths (34 089) and the death rate (27.0/100 000) from liver cancer decreased in 2003. Hepatitis C virus (HCV)-related HCC represents 75% of all HCC in Japan. The incidence of HCC without hepatitis B surface antigen (HBsAg) or anti-HCV accounted for 7-12% of HCC in Japan andhalf of non-B non-C-HCC was of unknown origin. Geographically, HCC is more frequent in western than eastern Japan, and the death rates from HCC in each prefecture correlate with the prevalence of anti-HCV, but not with HBsAg prevalence. Interferon therapy for chronic hepatitis C has reduced the risk factors for development of HCC, especially among patients with sustained response.
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Affiliation(s)
- Takeji Umemura
- Department of Internal Medicine, Gastroenterology, and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
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Abstract
Retinoic acid (RA) appears to play an important role in the pathophysiology of liver disease. However, this role remains to be clarified in detail. To explore the role of RA in the liver, transgenic mice that express RA receptor (RAR) alpha-dominant negative form in hepatocytes under the control of albumin promoter and enhancer, were developed. At 4 months of age the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. The enzymes that are involved in mitochondrial beta-oxidation of fatty acids, including very-long-acyl-CoA dehydrogenase, long-acyl-CoA dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase, were downregulated; in contrast, the enzymes that are involved in peroxisomal beta-oxidation, including acyl-CoA oxidase and bifunctional enzyme, were upregulated. Expression of cytochrome p4,504a10, cytochrome p4,504a12, and cytochrome p4,504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H(2)O(2) and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinomaand adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RARalpha/beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.
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Affiliation(s)
- Goshi Shiota
- Division of Molecular and Genetic Medicine, Department of Genetic Medicine and, Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
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10
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The Liver Cancer Study Group of Jap. The 16th national follow-up survey report on primary hepatic cancer (2000-2001). ACTA ACUST UNITED AC 2005. [DOI: 10.2957/kanzo.46.234] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Yanagitani A, Yamada S, Yasui S, Shimomura T, Murai R, Murawaki Y, Hashiguchi K, Kanbe T, Saeki T, Ichiba M, Tanabe Y, Yoshida Y, Morino SI, Kurimasa A, Usuda N, Yamazaki H, Kunisada T, Ito H, Murawaki Y, Shiota G. Retinoic acid receptor alpha dominant negative form causes steatohepatitis and liver tumors in transgenic mice. Hepatology 2004; 40:366-75. [PMID: 15368441 DOI: 10.1002/hep.20335] [Citation(s) in RCA: 114] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Although attention has focused on the chemopreventive action of retinoic acid (RA) in hepatocarcinogenesis, the functional role of RA in the liver has yet to be clarified. To explore the role of RA in the liver, we developed transgenic mice expressing RA receptor (RAR) alpha- dominant negative form in hepatocytes using albumin promoter and enhancer. At 4 months of age, the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes, including VLCAD, LCAD, and HCD, were down-regulated; on the other hand, peroxisomal beta-oxidation and its related enzymes, including AOX and BFE, were up-regulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinoma and adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RAR alpha/ beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.
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Affiliation(s)
- Atsushi Yanagitani
- Department of Genetic Medicine and Regenerative Therapeutics, Tottori University, Yonago, Japan
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12
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Zhao WH, Ma ZM, Zhou XR, Feng YZ, Fang BS. Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score. World J Gastroenterol 2002; 8:237-42. [PMID: 11925599 PMCID: PMC4658358 DOI: 10.3748/wjg.v8.i2.237] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection.
METHODS: A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 mo after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (≤ 3 year) and late (> 3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the χ² test, the Kaplan-Meier estimation and the COX proportional hazards model respectively.
RESULTS: The 1-, 3-, 5-, 7-, and 10-year disease-free survival rates after curative resection of HCC were 57.2%、28.3%、23.5%、18.8% and 17.8%, respectively. Median survival time was 28, 16, 10, 4, and 5 mo for CLIP score 0, 1, 2, 3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the χ² test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (≤ or > 50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages.
CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.
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Affiliation(s)
- Wen-He Zhao
- Department of Oncosurgery, the First Affiliated Hospital, Zhejiang University, Medical College, 79 Qingchun, Hangzhou 310003, Zhejiang Province, China.
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Amemiya T, Hayashida H, Dake Y. Metastatic orbital tumors in Japan: a review of the literature. Ophthalmic Epidemiol 2002; 9:35-47. [PMID: 11815894 DOI: 10.1076/opep.9.1.35.1718] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
A review of reports on metastatic orbital tumors published from 1903 to 1998 in Japan revealed 128 patients, 74 males, 52 females and 2 whose sex was not recorded. The average age was 44.8 years, but varied depending on the primary tumor. Since 1980, metastatic orbital tumors have increased in Japan, especially those from the lung, liver and adrenal gland, while metastasis from the stomach has decreased slightly. Metastasis from the breast is still common. Most metastatic orbital tumors were from the lung, followed, in order, by breast, liver, adrenal gland and stomach. Males had four times as many metastatic orbital tumors from lung cancer than did females; only females had metastases from breast cancer; almost 90% of metastases from hepatoma were in males; metastasis from renal carcinoma was 2-3 times more common in males than in females. Metastasis from the liver and stomach is seen more frequently in Japan than in the United States and Europe. Ocular signs due to orbital metastases from hepatoma, neuroblastoma and gastric cancer were apt to appear earlier than the signs of the primary lesion. Metastases to the orbit were frequently bilateral in patients with neuroblastoma and malignant lymphoma. Specific ocular signs such as ecchymosis and conjunctival hemorrhages were seen in orbital metastasis from neuroblastoma and seminoma, while ocular pain was characteristic of malignant lymphoma. Orbital metastasis was very rare in patients with carcinoma of the uterus, ovaries, bladder, pancreas, colon or rectum in both Japan, the United States and Europe.
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Affiliation(s)
- Tsugio Amemiya
- Department of Ophthalmology, Nagasaki University School of Medicine, Nagasaki-shi, Japan.
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Tsutusmi A, Shiota G, Yamazaki H, Kunisada T, Terada T, Kawasaki H. Accelerated growth of hepatocytes in association with Up-regulation of cyclin E in transgenic mice expressing the dominant negative form of retinoic acid receptor. Biochem Biophys Res Commun 2000; 278:229-35. [PMID: 11071877 DOI: 10.1006/bbrc.2000.3786] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Retinoids play an important role in pathogenesis of liver diseases. To clarify the functional role of retinoic acid (RA) in liver, we developed transgenic mice (Tg) which express the dominant negative form of retinoic acid receptor (RARE) in liver. Here, we report that proliferation of hepatocytes in RARE Tg is greatly enhanced and that cyclin E is up-regulated in RARE Tg. Liver weight, liver/body weight, and proliferating cell nuclear antigen (PCNA) labeling index in RARE Tg were significantly increased, compared to those in wild-type mice (P < 0.01, each). Cell cycle analysis showed that 2N DNA content cells and aneuploid area between 2N and 4N DNA, reflecting S phase cells, were significantly increased in RARE Tg, compared to wild-type mice (P < 0.01, each). Of G1 phase-related proteins including cyclins, cyclin-dependent protein kinases (CDKs) and cyclin-dependent protein kinase inhibitors (CKIs), cyclin E mRNA and protein was up-regulated in liver from RARE Tg by reverse transcription polymerase chain reaction and Western blot analysis. Furthermore, the immunoprecipitation with anti-cdk2 antibody, followed by Western blot analysis with anti-cyclin E antibody indicated that cyclin E/cdk2 complex is increased in liver of RARE Tg. The results of the present study suggest that cyclin E in association with cdk2 governs cell cycle progression through G1 in hepatocytes where function of RA is inhibited.
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Affiliation(s)
- A Tsutusmi
- Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
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15
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Guo WJ, Yu EX. Evaluation of combined therapy with chemoembolization and irradiation for large hepatocellular carcinoma. Br J Radiol 2000; 73:1091-7. [PMID: 11271902 DOI: 10.1259/bjr.73.874.11271902] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The effects of combined transcatheter arterial chemoembolization (TACE) and radiotherapy in patients with large hepatocellular carcinoma (HCC) were analysed retrospectively. A total of 107 patients with large unresectable HCC was treated with TACE followed by external beam irradiation. The largest dimension of the tumours ranged from 5 cm to 18 cm. Acute effects, survival rates, toxicity and prognostic factors were analysed. Follow-up ranged from 4 months to 98 months (median 24 months). An objective response, i.e. reduction of tumour area greater than 50%, was achieved in 48.6% of cases. In 64.9% of the cases with increased alpha-feto protein (AFP) values, AFP level underwent a reduction of more than 25%. The cumulative survival rates at 1, 3 and 5 years were 59.4%, 28.4% and 15.8%, respectively (median survival 18 months). The combination therapy was generally well tolerated. Only two patients died from liver failure or variceal bleeding associated with therapy. The Cox proportional hazards model showed that the number of tumours and the irradiation dose were independent prognostic factors. The results indicate that combined TACE with radiotherapy is a promising therapeutic approach for large unresectable HCC. Prospective controlled trials to ascertain the real potential benefit of this approach are required.
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Affiliation(s)
- W J Guo
- Department of Radiotherapy, Xinhua Hospital of Shanghai Second Medical University, 1665 Kongjiang Road, Shanghai, China 200092
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16
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Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H. Incidence of primary cholangiocellular carcinoma of the liver in japanese patients with hepatitis C virus-related cirrhosis. Cancer 2000; 88:2471-7. [PMID: 10861422 DOI: 10.1002/1097-0142(20000601)88:11<2471::aid-cncr7>3.0.co;2-t] [Citation(s) in RCA: 197] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma. However, the risk factors for primary cholangiocellular carcinoma of the liver (PCC-L) have not been fully investigated. The authors determined the incidence of PCC-L in patients with HCV-related cirrhosis. METHODS Between 1980 and 1997, the authors prospectively studied 600 consecutive patients for the appearance of PCC-L; these patients were positive for HCV and later developed cirrhosis. The follow-up period ranged from 0 to 18.5 years (median, 7.2 years). RESULTS During the observation period, PCC-L developed in 14 patients (2.3%). Among these, 11 (1.8%) had cholangiocellular carcinomas and the other 3 (0.5%) had a combined type of hepatocellular and cholangiocellular carcinoma. Within the same period, hepatocellular carcinoma (HCC) developed in 206 patients (34.3%). The cumulative rates of newly diagnosed PCC-L were 1.6% at 5 years and 3.5% at 10 years, which was about 1000 times higher than the estimated incidence of PCC-L in the general population of Japan. PCC-L was treated by surgical resection in 3 patients who survived for > 3 years. However, the other 11 patients received palliative therapy or chemotherapy. The survival rates among PCC-L patients were 39.3%, 23. 6%, and 16.5% at the end of 1, 3, and 5 years, respectively, and were significantly lower than those of HCC (P = 0.0001). CONCLUSIONS The results of this study show a relatively high incidence of PCC-L in patients with HCV-related cirrhosis, and also show that this type of liver cancer is associated with a relatively poor prognosis. These results indicate that HCV-related cirrhosis is a major risk factor for PCC-L in Japanese patients.
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Affiliation(s)
- M Kobayashi
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
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17
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Kawamoto C, Ido K, Isoda N, Nagamine N, Hozumi M, Ono K, Nakazawa Y, Sato Y, Kimura K. Prognosis of small hepatocellular carcinoma after laparoscopic ethanol injection. Gastrointest Endosc 1999; 50:214-20. [PMID: 10425415 DOI: 10.1016/s0016-5107(99)70227-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Most patients with hepatocellular carcinoma have underlying cirrhosis, and this impairment of liver function makes hepatectomy difficult, prompting the use of other modalities such as transcatheter arterial embolization and percutaneous ethanol injection. METHODS Laparoscopic ethanol injection was performed in 48 previously untreated patients with hepatocellular carcinoma smaller than 2 cm in diameter. Long-term survival was evaluated. RESULTS In 12 patients, hepatocellular carcinoma was not detected by trans-cutaneous ultrasonography but could be demonstrated by laparoscopic ultrasonography. Laparoscopic ethanol injection did not cause serious complications in any patient. The mean hospital stay after ethanol injection was 8.6 days (4 to 15 days). The cumulative survival rate was 86.7% at 3 years and 60.0% at 5 years. According to the Child-Pugh classification, the cumulative survival rate at 5 years was 87.9% for class A, 65.7% for class B, and 28.6% for class C. CONCLUSIONS The long-term prognosis for patients with small hepatocellular carcinoma treated solely by laparoscopic ethanol injection is satisfactory but still dependent on underlying liver function.
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Affiliation(s)
- C Kawamoto
- Department of Gastroenterology, Jichi Medical School, Tochigi, Japan
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18
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Tang ZY, Zhou XDA, Ma ZC, Wu ZQ, Fan J, Lin ZY, Lu JZ, Liu KDA, Ye SL, Yang BH. Multimodality treatment of hepatocellular carcinoma. J Gastroenterol Hepatol 1998; 13:S315-S319. [PMID: 28976647 DOI: 10.1111/j.1440-1746.1998.tb01901.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
By 1996, 2898 patients with pathologically proven hepatocellular carcinoma (HCC) had been treated at the Liver Cancer Institute of Shanghai Medical University. The 5 year survival in the entire series was 36.2%, being increased from 4.8% in 1958-70, 12.2% in 1971-83, to 50.5% in 1984-96 and 274 patients had survived more than 5 years. The increase in the survival rate could be attributed to the decreasing mean tumour diameter (11.7, 10.5 and 9.5 cm, respectively) and multimodality treatment. In addition to small HCC resection (5 year survival 64.9%, n = 735) and large HCC resection (5 year survival 37.4%, n = 1050), the following deserves to be mentioned. First, the 5 year survival of unresectable HCC treated by palliative surgery increased from 0% to 7.2% to 20.0%, which was related to the increase in use of multimodality treatment, particularly in those followed by second-stage resection. Second, cytoreduction and sequential resection is a new field with a significant potential in the treatment of localized unresectable HCC in a cirrhotic liver. Cytoreduction can be achieved by surgery, such as hepatic artery ligation, cannulation, cryosurgery and their combination, and followed by intrahepatic arterial chemoembolization, targeting therapy or regional radiotherapy. Ninety of 647 patients with unresectable HCC so treated had marked shrinkage of tumour and received second-stage resection; the 5 year survival was 71.4%. Third, non-surgical cytoreduction was mainly achieved by transcatheter arterial chemoembolization (TACE); for 70 patients with second-stage resection following TACE, the 5 year survival was 56.0%. Finally, re-resection of subclinical recurrence of tumour after curative HCC resection was performed in 155 patients; the 5 year survival calculated from the first resection was 50.9%, which played an important role in increasing the 5 year survival in the resection group (from 13.0% to 29.5% to 56.2%). It is concluded that multimodality treatment with combined and sequential use of different modalities and repeated use of some modalities is of substantial benefit for localized unresectable HCC.
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Affiliation(s)
- Zhao-You Tang
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Xin-DA Zhou
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Zeng-Chen Ma
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Zhi-Quan Wu
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Jia Fan
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Zhi-Ying Lin
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Ji-Zhen Lu
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Kang-DA Liu
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Sheng-Long Ye
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
| | - Bing-Hui Yang
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China
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Saito H, Ebinuma H, Takahashi M, Kaneko F, Wakabayashi K, Nakamura M, Ishii H. Loss of butyrate-induced apoptosis in human hepatoma cell lines HCC-M and HCC-T having substantial Bcl-2 expression. Hepatology 1998; 27:1233-40. [PMID: 9581676 DOI: 10.1002/hep.510270508] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
We have demonstrated that sodium butyrate induces differentiation in human hepatoma cells; however, recent studies have shown that this agent causes apoptosis in some types of cancer cells. In this study, we examined whether sodium butyrate causes apoptosis in the human hepatoma cell lines, HCC-M and HCC-T. The growth of human hepatoma cells was dose-dependently reduced by sodium butyrate. Flow cytometric analysis showed cell-cycle arrest at the G1 phase in the sodium butyrate-treated cells. Apoptotic change was never found in treated cells at concentration levels of less than 5 mmol/L. Sodium butyrate decreased p53 expression and increased p21WAF-1 expression in HCC-T and HCC-M cells having the wild-type p53 gene. Western blot analysis showed that Bcl-2 was expressed in the HCC-T and HCC-M cells, and its expression was increased after exposure to sodium butyrate. Antisense oligodeoxynucleotide against bcl-2 easily caused apoptosis. These results indicate that sodium butyrate hardly induces apoptotic change in the human hepatoma cell lines, HCC-T and HCC-M, with the increase of Bcl-2 expression. Cell-cycle arrest in the G1 phase caused by sodium butyrate was suggested to be induced by the increase in p21WAF-1 expression, but this change did not link with the p53 increase.
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Affiliation(s)
- H Saito
- Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
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20
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Une Y, Haneda T, Ogasawara K, Shimamura T, Matsushita M, Nakanishi K, Nakajima Y. Preoperative percutaneous transhepatic portal embolization with absolute ethanol in patients with hepatocellular carcinoma. ACTA ACUST UNITED AC 1997. [DOI: 10.1007/bf02488971] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Ido K, Isoda N, Kawamoto C, Hozumi M, Suzuki T, Nagamine N, Nakazawa Y, Ono K, Hirota N, Hyodoh H, Kimura K. Laparoscopic microwave coagulation therapy for solitary hepatocellular carcinoma performed under laparoscopic ultrasonography. Gastrointest Endosc 1997; 45:415-20. [PMID: 9165326 DOI: 10.1016/s0016-5107(97)70155-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- K Ido
- Department of Gastroenterology, Jichi Medical School, Tochigi, Japan
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22
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Kuwana K, Ichida T, Kamimura T, Ohkoshi S, Ogata N, Harada T, Endoh K, Asakura H. Risk factors and the effect of interferon therapy in the development of hepatocellular carcinoma: a multivariate analysis in 343 patients. J Gastroenterol Hepatol 1997; 12:149-155. [PMID: 9083916 DOI: 10.1111/j.1440-1746.1997.tb00398.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The aims of the present study were to clarify the risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection and to investigate the effectiveness of interferon (IFN) therapy. We retrospectively studied 343 patients who had been admitted to our hospital; 161 with chronic hepatitis, 49 with liver cirrhosis, 42 with chronic hepatitis bearing HCC and 91 with liver cirrhosis bearing HCC. The mean (+/- SD) observation period was 41.6 +/- 31.1 months. The mean age of HCC and non-HCC patients was 63.5 +/- 7.6 and 56.9 +/- 12.5 years, respectively (P < 0.001). The HCV genotype II (1b) was the most prevalent genotype (92.5%) in HCC patients and the mean age was higher among patients with this genotype (63.6 +/- 7.7 years). Multivariate analysis identified age (P < 0.001), the male gender (P < 0.01), HCV genotype II (1b) (P < 0.05) and excessive alcohol intake (P < 0.05) as independent factors associated with the development of HCC. There was no relationship between the development of HCC and serum HCV levels as quantified by branched DNA assay or competitive reverse transcription polymerase chain reaction. The incidence of HCC in patients who had not received IFN therapy was 10.4/100 person-year, while that of patients who had received IFN therapy was 1.2/100 person-year (P < 0.01) by the person-year method. The low incidence of HCC in patients treated with IFN suggests that IFN may prevent the development of HCC.
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Affiliation(s)
- K Kuwana
- Department of Internal Medicine III, Niigata University School of Medicine, Japan
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23
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Onodera H, Ukai K, Suzuki M, Minami Y. Incidence of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C. TOHOKU J EXP MED 1997; 181:275-83. [PMID: 9163844 DOI: 10.1620/tjem.181.275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We examined the effect of interferon (IFN) therapy for chronic active hepatitis (CAH) C in 207 patients by estimating the incidence of hepatocellular carcinoma (HCC) after IFN therapy using the person-years method. Statistical analysis was performed using the Mantel-Haenszel chi-square test. No HCC was detected in patients with normal serum alanine aminotransferase (ALT) levels after IFN therapy (response-effect group), and in patients with both normal serum ALT levels and hepatitis C virus (HCV)-RNA clearance after IFN therapy (complete-responder group). The incidence per 100,000 person-years in the patients with elevated serum ALT level after IFN therapy (other-effects group) were 1968 and 1624, respectively. The incidence in control patients who did not achieve IFN therapy was 901. No statistically significant differences were observed between the other-effects group, non-responder group, and the control group. Our results so far suggest that normalization of the serum ALT levels and/or HCV clearance might reduce the incidence of HCC.
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Affiliation(s)
- H Onodera
- Department of Internal Medicine, Miyagi Cancer Center, Japan
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Shimamura T, Nakajima Y, Une Y, Namieno T, Ogasawara K, Yamashita K, Haneda T, Nakanishi K, Kimura J, Matsushita M, Sato N, Uchino J. Efficacy and safety of preoperative percutaneous transhepatic portal embolization with absolute ethanol: a clinical study. Surgery 1997; 121:135-41. [PMID: 9037224 DOI: 10.1016/s0039-6060(97)90282-8] [Citation(s) in RCA: 110] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Preoperative portal embolization has been performed by using various thrombogenic substances to increase the safety and resectability of liver surgery. We evaluated the clinical safety and efficacy of using absolute ethanol in preoperative portal embolization. METHODS Our study included 19 patients who had undergone right hepatic lobectomy. According to our criteria for right lobectomy of the liver, seven patients were not appropriate for the operation because of a high risk in each of postoperative liver failure. Those patients received preoperative right portal embolization with 11 to 32 ml absolute ethanol. The remaining 12 patients satisfied our criteria and received no preoperative embolization. RESULTS Although alanine aminotransferase concentrations increased dramatically after the embolization, all serologic changes reverted within 3 weeks. The mean volume of the nonembolized lobe increased from 320 cm3 to 619 cm3 and 667 cm3 2 and 4 weeks, respectively, after embolization. The mean regeneration rate of this lobe was 21.3 cm3 per day for the first 2 weeks and 11.4 cm3 per day for the first 4 weeks after embolization. All patients underwent right lobectomy of the liver and survived; none of the patients had severe complications associated with embolization or surgery. The postoperative survival periods were not statistically significant between the patients with and without preoperative portal embolization. CONCLUSIONS According to our criteria for liver surgery, the seven patients should not have undergone major surgery, but each underwent right lobectomy of the liver and all survived, showing that portal embolization with absolute ethanol brings about compensatory hepatic hypertrophy for major surgery and that its extreme effect on liver regeneration could widen the range of patients appropriate for liver surgery.
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Affiliation(s)
- T Shimamura
- First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan
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Fukukura Y, Taguchi J, Nakashima O, Wada Y, Kojiro M. Combined hepatocellular and cholangiocarcinoma: correlation between CT findings and clinicopathological features. J Comput Assist Tomogr 1997; 21:52-8. [PMID: 9022770 DOI: 10.1097/00004728-199701000-00011] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE The purpose of this study was to clarify characteristics of combined hepatocellular and cholangiocarcinoma (HCC-CC) on CT and clinicopathological examinations. METHODS Dynamic incremental CT was performed on 15 combined HCC-CC patients. CT of the early phase was started at 30 s and of the late phase at 120-140 s, after the start of contrast medium injection at a rate of 3 ml/s. The images and clinicopathological findings were retrospectively compared. RESULTS Lesions grossly resembling HCC (HCC type, n = 6) were well enhanced in the early phase and changed to low attenuation areas in the late phase. In lesions grossly resembling CC (CC type, n = 9), 8 of 9 lesions were enhanced only at the peripheral portions in the early phase and changed to low attenuation areas or had only central portions enhanced in the late phase. The other CC-type lesion was not enhanced in either the early or the late phase. In all 15 cases, there was no dilatation of the intrahepatic bile ducts. Hepatitis B virus surface antigen was positive in five cases. Hepatitis C virus antibody was positive in 10 cases. Serum alpha-fetoprotein (AFP) levels were > or = 200 ng/ml in seven cases. CONCLUSION In the CC type, enhanced CT images were compatible with CC, but positivities for virus markers and serum AFP levels were almost equivalent to those in HCC. Therefore, the CC type can be diagnosed as combined HCC-CC by evaluating virus markers and serum AFP levels with CT. In addition, no association of intrahepatic bile duct dilatation was considered to be a characteristic feature of combined HCC-CC.
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Affiliation(s)
- Y Fukukura
- First Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan
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Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki KT, Tanaka T, Tsurumi K, Okuno M, Tomita E, Nakamura T, Kojima T. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 1996; 334:1561-7. [PMID: 8628336 DOI: 10.1056/nejm199606133342402] [Citation(s) in RCA: 472] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. METHODS We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. RESULTS Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78). CONCLUSIONS Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.
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Affiliation(s)
- Y Muto
- First Department of Internal Medicine, Gifu University School of Medicine, Japan
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