Primary Liver Cancer In Japan Research Articles

Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015).

For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20889 newly registered patients and 42274 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.

Molecular characterization-based multi-omics analyses in primary liver cancer using the Japanese version of the genome atlas.

Primary liver cancer (PLC) is classified into hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular and intrahepatic cholangiocarcinoma (CHC). We investigated the genomic landscape of PLC according to the histological classification and established a cross-histological molecular subtyping for PLC by a multi-omics analysis. We analyzed 265 PLC cases with whole-exome sequencing and DNA copy number analyses and 251 cases with gene expression profiling. The cohort included HCC (n=223, 84%), ICC (n=34, 13%), and CHC (n=8, 3%). Mutation analyses identified histological type-specific driver genes, such as CTNNB1 in HCC and KRAS, IDH1, and PIK3CA in ICC, and ARID1A and KMT2C in CHC. The tumor suppressor gene TP53 mutation was detected in 21.1% of HCC, 16.1% of ICC, and 25.0% of CHC cases. Other well-characterized tumor suppressor genes included RB1, which was mutated in 2.8% of HCC and 3.2% of ICC; and PTEN, which was mutated in 1.4% of HCC, 3.2% of ICC, and 12.5% of CHC cases. DNA copy number analyses identified focal amplifications, with NUF2 (1q23.3) the most frequently detected as an amplified gene in all 3 types (HCC, 3.8%; CHC, 12.5%, ICC, 3.2%). Molecular subtyping for PLC based on the multi-omics analysis identified three subtypes, one of which was associated with recurrence after resection and amplified genes located at chromosome 8q. Our dataset serves as a fundamental resource for genomic medicine for PLC in Japan and identified amplified genes located at chromosome 8q as promising therapeutic targets for the subgroup with a poor prognosis.

Current status of primary liver cancer and decompensated cirrhosis in Japan: launch of a nationwide registry for advanced liver diseases (REAL).

We developed a nationwide database that stores data of patients with primary liver cancer (PLC) and decompensated cirrhosis (DC) on an admission basis. A database was constructed using the National Clinical Database, a nationwide registry platform for various diseases in Japan. Mutual data exchange was possible with the Nationwide Follow-up Survey of Primary Liver Cancer in Japan by the Liver Cancer Study Group of Japan. The stored data on the admission of patients with PLC, DC, or both, included treatment details as well as patient characteristics. A total of 37,705 admissions (29,489 PLC, 10,077 DC, and 1862 for both) in 21,376 patients from 224 hospitals were analyzed. The proportions of patients with hepatitis B, hepatitis C, and non-viral etiology were 11.9%, 36.2%, and 42.6%, respectively, in PLC, and 7.5%, 23.8%, and55.0%, respectively, in DC. The mean ages (± standard deviation) on admission with PLC and DC were 73 ± 10 and 68 ± 13years, respectively. The Barcelona Clinic Liver Cancer (BCLC) stage for PLC was 0, A, B, C, and D in 22.0%, 17.1%, 29.6%, 15.1%, and 5.1%, respectively. Treatment modalities for PLC were resection, ablation, transarterial chemoembolization, and systemic therapy in 18.4%, 22.8%, 33.7%, and 11.4%, respectively. A vasopressin receptor V2 antagonist was used in 38.2% in addition to conventionally used loop diuretics and aldosterone antagonists for DC. The distribution of treatment options for PLC on admission differed from that of the initial treatment. Newly introduced drugs are widely used in patients with DC.

Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013).

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.

Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011).

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.

Hepatic Resection for Hepatocellular Carcinoma in the Era of Molecular-targeted Agents and Immune Checkpoint Inhibitors in Japan.

Hepatic resection or liver transplantation for hepatocellular carcinoma (HCC) represents the only chance for achieving a cure. For the past several decades in Japan, aggressive hepatic resection has been performed for advanced HCC, with consequent good outcomes. According to the 21st Nationwide Follow-Up Survey of Primary Liver Cancer in Japan, 38.3% of patients were treated with hepatic resection or liver transplantation as the initial treatment. The median overall survival of patients who underwent surgery was 57.0 months, and the 5- and 10-year survival rates were 48.4% and 25.2%, respectively. Since 1964, a total of 10,038 liver transplants (595 deceased-donor and 9,443 living-donor transplants) have been performed in Japan. Neoplastic disease, including HCC, was reported to be the third-most common cause of liver transplantation, and the cumulative 1-, 3-, 5-, and 10-year survival rates of living-donor liver transplants for HCC were 85.0%, 76.2%, 70.9%, and 63.1%, respectively. However, molecular-targeted agents, including sorafenib and lenvatinib, have recently been developed. Furthermore, a significantly longer survival with atezolizumab, which is an immune checkpoint inhibitor, plus bevacizumab was observed compared with sorafenib for unresectable HCC patients. Herein, we review the current status of hepatic resection and liver transplantation for HCC in Japan and discuss the role of hepatic resection in the era of molecular-targeted agents and immune checkpoint inhibitors, as well as the need for a definition of borderline resectable-HCC.

Report of the 20th Nationwide follow-up survey of primary liver cancer in Japan.

In the 20th Nationwide Follow‐up Survey of Primary Liver Cancer in Japan, data from 21 075 new patients and 40 769 previously followed patients were compiled from 544 institutions over a 2‐year period from 1 January 2008 to 31 December 2009. Compared with the previous 19th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, included more female patients, included more patients with non‐B non‐C HCC, had smaller tumor diameters and more frequently received radiofrequency ablation as local ablation therapy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and by background characteristics for patients newly registered between 1998 and 2009 whose final outcome was survival or death. 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 types (hepatectomy, local ablation therapy, and transcatheter arterial chemoembolization). Cumulative survival rates and median overall survival in patients treated by resection, transcatheter arterial chemoembolization, and local ablation therapy were calculated. The same values were also calculated by the registration date by dividing patients newly registered between 1978 and 2009 into four time period groups . The results of the analysis show that the prognosis of HCC is improving dramatically. It is expected that the data obtained from this nationwide follow‐up survey will contribute to advancing clinical research, including the design of clinical trials, as well as the treatment strategy of primary liver cancer in the clinical practice setting.

Report of the 19th 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 2years (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.

P1-14-1 - The Clinicopathological Features of Postoperative Extrahepatic Metastasis of Hcc After Hepatectomy

Introduction: Postoperative extrahepatic metastasis (EHM) of HCC is still difficult to treat. In this study, patients who had EHM of HCC after hepatectomy was analyzed and compared to patients who had intrahepatic metastasis (IHM).We clarified independent risk factors for postoperative EHM.Methods: A total of 350 cases who underwent liver resection for HCC during the period of 1991 through 2011 were retrospectively analyzed and clarified the clinicopathological features of the patients and independent risk factors for postoperative EHM. In addition, patients were divided into two groups (IHM group: patients with only IHM, EHM group: patients with only EHM or EHM and IHM) and compared between two groups.Results: The overall 5 years-survival rate of 350 patients was 67.6%.The median disease-free survival time of 350patients was 740 days. Postoperative metastasis was detected in 238 patients. Postoperative IHM cases were detected in 211 patients, and postoperative EHM cases were detected 27 patients. Compared EHM group(N = 27) with IHM group(N = 211), the 5 years-survival rate of IHM group was 67.6 %. Median disease-free survival time of IHM group was 428 days. The 5 years-survival rate of EHM group was 47.3%.The median disease-free survival time of EHM group was 234 days. The 5 years-survival rate of EHM is significance low rate compared with that of IHM (p < 0.05) . Tumor diameter, AFP, growth type, vessel invasion (General rules for the clinical and pathological study of primary liver cancer in Japan) were the independent factors predictive for a high risk for EHM in uniivariate analysis (p < 0.05). AFP, growth type, vessel invasion were the independent factors predictive for a high risk for EHM in multivariate analysis (p < 0.05).Conclusions: Postoperative extrahepatic metastasis of HCC result in worse rate of overall survival than that of intrahepatic metastasis. Close follow-up care is prudent for those patients who have high risk for EHM.

Current status of hepatocellular carcinoma in Japan.

Approximately 32,000 patients die of primary liver cancer each year in Japan. The annual number of deaths from primary liver cancer in Japan ranks second only to that in China in the world. In recent years, there has been a gradual trend towards decrease in the number of liver cancer patients from its peak in Japan, and this trend is expected to also continue in the future. The main reason for this decreasing trend was the establishment of screening of transfusion products for hepatitis B and hepatitis C viruses, which prevents transfusion-related transmission of the viral infection. Most patients with hepatocellular carcinoma (HCC) in Japan have underlying viral hepatitis, with hepatitis C accounting for about two-third of all the patients and hepatitis B accounting for about 15%. Regular screening of patients with viral hepatitis infection makes it possible to diagnose HCC early, and also enables effective loco-regional treatment, such as surgical resection, local ablative therapy and transcatheter arterial chemoembolization (TACE). However, HCC recurrence is encountered frequently even after these potentially effective treatments. After numerous loco-regional treatments for recurrent HCC, chemotherapy is administered for patients with highly advanced HCC. Among the modalities of chemotherapy, hepatic arterial infusion chemotherapy (HAIC) is employed more commonly than systemic chemotherapy, although no survival advantage has ever been demonstrated. Randomized controlled studies are currently under way to clarify the survival benefit of HAIC. Also, various novel systemic chemotherapeutic agents are currently under development in Japan, and further improvements in the treatment outcomes are expected.

Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan.

Background:The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear.Methods:The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy.Results:A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41–0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001).Conclusion:For advanced HCC, HAIC is considered to be an effective treatment.

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

In the 18th Nationwide Follow-Up Survey of Primary Liver Cancer in Japan, 20 753 people were newly registered as patients with primary liver cancer at 544 medical institutions over a period of 2 years (from 1 January 2004 to 31 December 2005). Of these patients, 94.0% had hepatocellular carcinoma (HCC) and 4.4% had intrahepatic cholangiocarcinoma (ICC). In addition, 30 677 follow-up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients. Compared with the 17th follow-up survey, this follow-up survey in HCC indicated an increase in elder patients and women, a decrease in patients positive for hepatitis B surface antigen and hepatitis C virus antibody, and a decrease in tumor size at the clinical diagnosis. In the local ablation therapy, ratio of radio frequency ablation therapy was increasing. The cumulative survival rates of newly-registered patients between 1994 and 2005 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The cumulative survival rates of newly-registered patients between 1978 and 2005 divided into three groups (1978-1985, 1986-1995 and 1996-2005) were also calculated. The data obtained in this follow-up survey should contribute to future research and medical practice for primary liver cancer.

Chapter 2: Diagnosis and surveillance

Chapter 2: Diagnosis and surveillance

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.

Clinicopathologic spectrum of resected extraductal mass-forming intrahepatic cholangiocarcinoma.

The mode of tumor growth of intrahepatic cholangiocarcinoma (CC) varies considerably from patient to patient. This study describes the clinicopathologic variety of the extraductal mass-forming type of CC. Patients with CC characterized by an extraductal mass (n = 26) who underwent hepatectomy from 1976 through 1992 were clinicopathologically classified into three types: Type I (n = 7), no biliary stricture; Type II (n = 13), biliary stricture without jaundice; and Type III (n = 6), biliary stricture with jaundice. Type I included three patients with microductular-trabecular arrangement and behavior reminiscent of hepatocellular carcinoma (high association with chronic liver disease, mild positivity for alpha-fetoprotein [AFP], no lymph node metastasis, but frequent intrahepatic metastasis), in contrast to the other typical cholangiocarcinoma. Hepatolithiasis was associated only with Type II CC: The serum positivity for AFP and carcinoembryonic antigen was much higher in Type I CC, whereas positivity of CA 19-9 was highest in Type III. Involvement of the portal vein, hepatic artery, or hepatic duct was most frequent in Type III CC, which necessitated resection of the extrahepatic bile duct and hepatectomy. The clinicopathologic behavior of intrahepatic CC differs considerably according to the presence or absence of stricture of the biliary tree. Thus, CC without biliary stricture behaves more like hepatocellular carcinoma, whereas CC with biliary stricture is more like hilar or extrahepatic bile duct carcinoma.

原発性肝癌に関する追跡調査 第１１報

全国536施設の協力により,1990年1月1日より1991年12月31日までの2年間に本邦における原発性肝癌11,916例が日本肝癌研究会に登録された.臨床診断による組織型内訳は,肝細胞癌11,379例,胆管細胞癌322例,嚢胞腺癌24例,混合型30例,肝芽腫8例,肉腫7例であった.本報告においては,これら症例を170項目におよぶ診断,治療,臨床病理学的事項等について解析し,その主たる点について述べた.さらに第5回(1978～1979年)以降の肝細胞癌の切除療法,肝動脈塞栓療法,そして経皮的エタノール注入療法を受けた症例の累積生存率を算出した.肝切除では,3年,5年累積生存率は各々,57.5%, 40.8%,肝動脈塞栓療法では各々,19.5%, 8.0%であった.エタノール注入療法の3年生存率は53.2%であった.また,今回の特別解析項目として,第5～第10調査のデータを基に肝切除の予後を予知する因子をCoxの比例ハザードモデルによる多変量解析とStepwise methodにより検討した.

Primary liver cancer in Japan. Edited by T. Tobe, H. Kameda, M. Okudaira, M. Ohto, Y. Endo, M. Mito, E. Okamoto, K. Tanikawa and M. Kojiro, 453 pp. Tokyo: Springer-Verlag, 1992. $278

HepatologyVolume 17, Issue 4 p. 753-753 Book ReviewFree Access Primary liver cancer in Japan. Edited by T. Tobe, H. Kameda, M. Okudaira, M. Ohto, Y. Endo, M. Mito, E. Okamoto, K. Tanikawa and M. Kojiro, 453 pp. Tokyo: Springer-Verlag, 1992. $278 Elliot Alpert M.D., Elliot Alpert M.D. Sir Mortimer B. Davis–Jewish General Hospital McGill University Montreal, Canada H3T 1E2Search for more papers by this author Elliot Alpert M.D., Elliot Alpert M.D. Sir Mortimer B. Davis–Jewish General Hospital McGill University Montreal, Canada H3T 1E2Search for more papers by this author First published: April 1993 https://doi.org/10.1002/hep.1840170436AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume17, Issue4April 1993Pages 753-753 RelatedInformation

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Primary Liver Cancer in Japan: Edited by T. TobeGastrointestinal Pathology and its Clinical Implications By Klaus J. Lewin, Robert H. Riddell and Wilfred M. WeinsteinIntroduction to Gastro‐intestional Endoscopy—Basic Principles and Practice. By John BaillieOxford Textbook of Clinical Hepatology. Edited by N. Mclntyre et al.Atlas of Gastrointestinal Endoscopy, 2nd edn. By F.E. Silverstein and G.N.J. Tytgat

原発性肝癌に関する追跡調査 第９報

原発性肝癌に関する追跡調査 第９報

原発性肝癌に関する追跡調査 ＶＩＩＩ

原発性肝癌に関する追跡調査 ＶＩＩＩ