- Email: [email protected]
in human hepatocellular carcinoma
HEPATOLOGYVol. 34, No. 4, Pt. 2, 2001
AASLD ABSTRACTS
677A
2019
2020
~THICH 1S CRITICAL PROBLEM, OCCULT HBV INFECTION OR MITOCHONDRIAL DNA MUTATION IN NON-B, NON-C HEPATOCELLULAR CARCINOMA IN JAPAN?. Akihiro Tamori, Shuhei Nishiguchi, Manabu
HEPATIC ARTERIAL INFUSION CHEMOTHERAPY FOR ADVANCED HEPATOCELLULAR CARCINOMA W I T H PORTAL VEIN TUMOR THROMBOSIS; ANALYSIS OF 39 CASES. Eiji Ando, Masatoshi Tanaka,
Nishikawa, Shoji Kubo, Takashi Narimatsu, Noritoshi Koh, Susumu Shiomi, Kazuhiro Hirohashi, Hiroaki Kinoshita, Masayasu Inoue, Shnzo Otani, Osaka City University Medical School, Osaka Japan
Kurume University School of Medicine, Kurume Japan; Fumihiko Yamashita, Saga Social Insurance Hospital, SagaJapan; Ryoko Kuromatsu, Naofumi Ono, Satoshi Itano, Riko Harada, Kazuta Fukumori, Shnji Sumie, Kurume University School of Medicine, Kurume Japan; Yoichi Yano, Saga Social Insurance Hospital, Saga Japan; Ryukichi Kumashiro, Michio Sara, Kurume University School of Medicine, Kurume Japan
In Japan, 80% of patients with hepatocellular carcinoma (HCC) were infected with HBV or HCV. It is elucidated that hepatitis virus protein has oncogenic effect to liver in transgenic mouse. But, there were a few reports about hepatocarcinogenesis of patients without HBV and HCV. Recently, mitochondrial DNA (mtDNA) mutations have been detected in human colorectal, neck, and thyroid cancers. Mutations of mtDNA are accumulated by stress of reactive o~ggen species, and are correlated to damage of nuclear DNA. By the way, HBV DNA was detected in liver tissue from patients without hepatitis B surface antigen (HBsAg) and it was suggested that so called occult HBV infection had some influences to HCV related HCC. To elucidate the effect of two factors in non-B, non-C HCC, we examined 18 HCC tissues without HBsAg and HCVAb. Surrounding fiver tissues showed fibrous change without one case. First, we amplified the entire mitochondrial genome by PCR and determined the sequence of the mitochondrial displacement (D)-loop with an Applied Biosysterns DNA sequencer. Next, we examined Transcripts of HBV-related RNA was amplified by reverse transcription and PCR. HBV-related RNA was detected in nine (50%) of 18 HCC tissues. In HBV-RNA positive group, there was no patient with alcohol abuse. On the other hand, there were four of 9 patients with alcohol abuse in HBV-RNA negative group. We detected muhi-mtDNA mutations in cancer (2-9 mutations in HCC). The average of detected mtDNA mutations was 4 in HBV-RNA positive group and 4.5 in negative group. Our results suggest that oxidative stress by chronic inflammation injured mtDNA and probably followed to nuclear DNA mutations in non-B, non-C HCC. In Japanese non-B, non-C patients with HCC, the etiology of chronic inflammation may be occult HBV infection (50%) and alcohol intake.
Back grounds and Aim: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for such advanced HCC. Methods: 39 patients with HCC with PVTT were treated with HAIC via an subcutaneously implanted injection port. Of these, 11 patients had PVTT in the second portal branch, and 28 patients had PVTT in the third portal branch or in the main portal trunk. One course consisted of daily administration of cisplatin (10 mg for 1 hour on Days 1-5) followed by the subsequent 5-f!uorouracil (250 mg for 5 hours on days 1-5). Patients were to receive four serial courses of FLMC. Responders were defined as complete response (CR) or partial response (PR). Factors related to survival was determinated by Kaplan-Meier method and Cox proportional hazard model Results: After HAIC, 9 and 9 patients had CR and PR, respectively (response rate=46 %). 1-year, 2-year, 3-year, and 5-year cumulative survival rate of 39 patients was, 44%, 31%, 28 %, and 19 %, respectively. Prognostic factors analyzed by univariate analysis, were therapeutic effect (responders vs non-responders) and hepatic reserve capacity- (Child A vs Child B or Child C), but the degree of PVTT was not a significant prognostic factor. Multivariate analysis showed that only" therapeutic effect was related to survival. Conclusions: HAIC using low dose cisplatin and 5-fluorouracil may be an usefull option for advanced HCC with PVTT. Patients with better hepatic reserve capacity are suitable candidates for HAIC.
2021
2022
CHILD-PUGH SCOREAND NOT SIZEAND NUMBER OF TUMORS ARE PROGNOSTIC FACTORS FOR HEPATO-CELLULAR CARCINOMA. Fed-
REDUCED EXPRESSION OF THE ATP-B1NDING CASSETTE TRANSPORTER SUPERFAMILY G E N E / M R P 2 / I N HUMAN HEPATOCELLULAR CARCINOMA. Ken-Ichi Taguchi, Eiji Hinoshita, Mitsuo Shimada, Keizo Sugi-
erica Dondero, Pierre Rufat, Jean Marc Regimbeau, Elisabeth Kimmoun, Fleur Nguyenphukai, Valerie Vilgrain, Dominique Valla, Jacques Belghiti, Francoise Degos, Hopital Beaujon, AP-HP, Clichy France Background :The incidence of hepatoceflular carcinoma (HCC) is increasing in Europe. Early detection is proposed to improve the prognosis, and the medical care of these patients should take into account the present characteristics of the disease. Aimof the study: re-assess the prognostic factors of HCC on a series of 400 consecutive French patients, hospitalized in the same medico-surgical center. Methods: Between Jan 1996 and June 2000, we studied the epidemiological, clinical, radiological data of a series of 400 patients. The number and size of the tumors were determined by helical CT with iodine injection and/or MRI. The diagnosis of HCC was assessed either on histological examination (59%) or increased AFP>400ng:ml (36%) and/or portal thrombosis associated with hypervascular tumor in others. Survival was assessed with the Cox model, with a minimal one year follow-up. Results: The mean age was 59.6-+ 12 years, 78% of the patients were males, overall mean survival was 353 -+152 days. The mean size of nodules was 49 -+40 mm, (44% < 30mm, 33% > 50mm), 60% of patients had one single nodule (among which 53% with diameter< 30mm) at presentation and 18% had more than 3 nodules. The etiology of underlying liver disease was alcohol in 20.5%, hepatitis B virus infection in 15.5%, hepatitis C virus infection in 38.5% and others in 24%. Survival was related mainly with Child-Pugh score at presentation (HR 0.4, 95%CI 0.34-0.54) and alcoholic underlying liver disease ((HR:I.4, 95%CI 1.13-i.89), and not with the size, nor the number of nodules, or the type of trea,Lment. By multivariate analysis the Child score was the only independent factor associated with survival (HR: 0.45, 95%CI 0.3-0.57). Conclusion: The results of this study emphasize the major importance of liver function assessment and determination of underlying liver disease for evaluation of the prognosis of HCC. Therefore detection methods should be focused only on the group of cirrhotic patients with good liver function, and therapeutic decisions should rely not only on the characteristics of the tumor but also on the evaluation of liver function.
machi, Michihiko Kuwano, Masazumi Tsuneyoshi, Kyushu University, Fukuoka Japan Background & Aims: The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein (PGP)/muhidrug resistantance (MDR) 1 and MDR protein (MRP) 1, is often upregulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. PGP and MRP2, known as one of human MRP subfamily members with structural similarities to MRP1, are localized canaficular (apical) plasma membrane domains. To understand expression of MDR1 and MRP2 in hepatocellular carcinoma (HCC), determination of the liver-specific function at the molecular level is critical. Methods: We examined the protein and mRNA expression of MDR1 and MRP2, in non-cancerous and cancerous regions in the liver of 33 patients with HCCs using immunohistochemical staining and quantitative RT-PCR analysis. Results: Tumor tissues expressed PGP and MRP2 on the canalicular membrane. A significant difference in protein expression of PGP and MRP2 was observed between non-cancerous and cancerous regions, however, no significant difference of mRNA expression was recognized. Conclusions: A significant reduction in PGP and MRP2 expression existed in cancerous region of HCC. The reduced expression of PGP and MRP2 in HCC might be related to posttranseriptional regulation.
AASLD ABSTRACTS
677A
2019
2020
~THICH 1S CRITICAL PROBLEM, OCCULT HBV INFECTION OR MITOCHONDRIAL DNA MUTATION IN NON-B, NON-C HEPATOCELLULAR CARCINOMA IN JAPAN?. Akihiro Tamori, Shuhei Nishiguchi, Manabu
HEPATIC ARTERIAL INFUSION CHEMOTHERAPY FOR ADVANCED HEPATOCELLULAR CARCINOMA W I T H PORTAL VEIN TUMOR THROMBOSIS; ANALYSIS OF 39 CASES. Eiji Ando, Masatoshi Tanaka,
Nishikawa, Shoji Kubo, Takashi Narimatsu, Noritoshi Koh, Susumu Shiomi, Kazuhiro Hirohashi, Hiroaki Kinoshita, Masayasu Inoue, Shnzo Otani, Osaka City University Medical School, Osaka Japan
Kurume University School of Medicine, Kurume Japan; Fumihiko Yamashita, Saga Social Insurance Hospital, SagaJapan; Ryoko Kuromatsu, Naofumi Ono, Satoshi Itano, Riko Harada, Kazuta Fukumori, Shnji Sumie, Kurume University School of Medicine, Kurume Japan; Yoichi Yano, Saga Social Insurance Hospital, Saga Japan; Ryukichi Kumashiro, Michio Sara, Kurume University School of Medicine, Kurume Japan
In Japan, 80% of patients with hepatocellular carcinoma (HCC) were infected with HBV or HCV. It is elucidated that hepatitis virus protein has oncogenic effect to liver in transgenic mouse. But, there were a few reports about hepatocarcinogenesis of patients without HBV and HCV. Recently, mitochondrial DNA (mtDNA) mutations have been detected in human colorectal, neck, and thyroid cancers. Mutations of mtDNA are accumulated by stress of reactive o~ggen species, and are correlated to damage of nuclear DNA. By the way, HBV DNA was detected in liver tissue from patients without hepatitis B surface antigen (HBsAg) and it was suggested that so called occult HBV infection had some influences to HCV related HCC. To elucidate the effect of two factors in non-B, non-C HCC, we examined 18 HCC tissues without HBsAg and HCVAb. Surrounding fiver tissues showed fibrous change without one case. First, we amplified the entire mitochondrial genome by PCR and determined the sequence of the mitochondrial displacement (D)-loop with an Applied Biosysterns DNA sequencer. Next, we examined Transcripts of HBV-related RNA was amplified by reverse transcription and PCR. HBV-related RNA was detected in nine (50%) of 18 HCC tissues. In HBV-RNA positive group, there was no patient with alcohol abuse. On the other hand, there were four of 9 patients with alcohol abuse in HBV-RNA negative group. We detected muhi-mtDNA mutations in cancer (2-9 mutations in HCC). The average of detected mtDNA mutations was 4 in HBV-RNA positive group and 4.5 in negative group. Our results suggest that oxidative stress by chronic inflammation injured mtDNA and probably followed to nuclear DNA mutations in non-B, non-C HCC. In Japanese non-B, non-C patients with HCC, the etiology of chronic inflammation may be occult HBV infection (50%) and alcohol intake.
Back grounds and Aim: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for such advanced HCC. Methods: 39 patients with HCC with PVTT were treated with HAIC via an subcutaneously implanted injection port. Of these, 11 patients had PVTT in the second portal branch, and 28 patients had PVTT in the third portal branch or in the main portal trunk. One course consisted of daily administration of cisplatin (10 mg for 1 hour on Days 1-5) followed by the subsequent 5-f!uorouracil (250 mg for 5 hours on days 1-5). Patients were to receive four serial courses of FLMC. Responders were defined as complete response (CR) or partial response (PR). Factors related to survival was determinated by Kaplan-Meier method and Cox proportional hazard model Results: After HAIC, 9 and 9 patients had CR and PR, respectively (response rate=46 %). 1-year, 2-year, 3-year, and 5-year cumulative survival rate of 39 patients was, 44%, 31%, 28 %, and 19 %, respectively. Prognostic factors analyzed by univariate analysis, were therapeutic effect (responders vs non-responders) and hepatic reserve capacity- (Child A vs Child B or Child C), but the degree of PVTT was not a significant prognostic factor. Multivariate analysis showed that only" therapeutic effect was related to survival. Conclusions: HAIC using low dose cisplatin and 5-fluorouracil may be an usefull option for advanced HCC with PVTT. Patients with better hepatic reserve capacity are suitable candidates for HAIC.
2021
2022
CHILD-PUGH SCOREAND NOT SIZEAND NUMBER OF TUMORS ARE PROGNOSTIC FACTORS FOR HEPATO-CELLULAR CARCINOMA. Fed-
REDUCED EXPRESSION OF THE ATP-B1NDING CASSETTE TRANSPORTER SUPERFAMILY G E N E / M R P 2 / I N HUMAN HEPATOCELLULAR CARCINOMA. Ken-Ichi Taguchi, Eiji Hinoshita, Mitsuo Shimada, Keizo Sugi-
erica Dondero, Pierre Rufat, Jean Marc Regimbeau, Elisabeth Kimmoun, Fleur Nguyenphukai, Valerie Vilgrain, Dominique Valla, Jacques Belghiti, Francoise Degos, Hopital Beaujon, AP-HP, Clichy France Background :The incidence of hepatoceflular carcinoma (HCC) is increasing in Europe. Early detection is proposed to improve the prognosis, and the medical care of these patients should take into account the present characteristics of the disease. Aimof the study: re-assess the prognostic factors of HCC on a series of 400 consecutive French patients, hospitalized in the same medico-surgical center. Methods: Between Jan 1996 and June 2000, we studied the epidemiological, clinical, radiological data of a series of 400 patients. The number and size of the tumors were determined by helical CT with iodine injection and/or MRI. The diagnosis of HCC was assessed either on histological examination (59%) or increased AFP>400ng:ml (36%) and/or portal thrombosis associated with hypervascular tumor in others. Survival was assessed with the Cox model, with a minimal one year follow-up. Results: The mean age was 59.6-+ 12 years, 78% of the patients were males, overall mean survival was 353 -+152 days. The mean size of nodules was 49 -+40 mm, (44% < 30mm, 33% > 50mm), 60% of patients had one single nodule (among which 53% with diameter< 30mm) at presentation and 18% had more than 3 nodules. The etiology of underlying liver disease was alcohol in 20.5%, hepatitis B virus infection in 15.5%, hepatitis C virus infection in 38.5% and others in 24%. Survival was related mainly with Child-Pugh score at presentation (HR 0.4, 95%CI 0.34-0.54) and alcoholic underlying liver disease ((HR:I.4, 95%CI 1.13-i.89), and not with the size, nor the number of nodules, or the type of trea,Lment. By multivariate analysis the Child score was the only independent factor associated with survival (HR: 0.45, 95%CI 0.3-0.57). Conclusion: The results of this study emphasize the major importance of liver function assessment and determination of underlying liver disease for evaluation of the prognosis of HCC. Therefore detection methods should be focused only on the group of cirrhotic patients with good liver function, and therapeutic decisions should rely not only on the characteristics of the tumor but also on the evaluation of liver function.
machi, Michihiko Kuwano, Masazumi Tsuneyoshi, Kyushu University, Fukuoka Japan Background & Aims: The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein (PGP)/muhidrug resistantance (MDR) 1 and MDR protein (MRP) 1, is often upregulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. PGP and MRP2, known as one of human MRP subfamily members with structural similarities to MRP1, are localized canaficular (apical) plasma membrane domains. To understand expression of MDR1 and MRP2 in hepatocellular carcinoma (HCC), determination of the liver-specific function at the molecular level is critical. Methods: We examined the protein and mRNA expression of MDR1 and MRP2, in non-cancerous and cancerous regions in the liver of 33 patients with HCCs using immunohistochemical staining and quantitative RT-PCR analysis. Results: Tumor tissues expressed PGP and MRP2 on the canalicular membrane. A significant difference in protein expression of PGP and MRP2 was observed between non-cancerous and cancerous regions, however, no significant difference of mRNA expression was recognized. Conclusions: A significant reduction in PGP and MRP2 expression existed in cancerous region of HCC. The reduced expression of PGP and MRP2 in HCC might be related to posttranseriptional regulation.