2003 Fiscal Year Annual Research Report

肝細胞癌の発癌・進展における腫瘍血管構築の精密血流画像解析とその分子機構の解明

Research Project

Project/Area Number	14570524
Research Institution	Kinki University
Principal Investigator	工藤正俊近畿大学, 医学部, 教授 (10298953)
Co-Investigator(Kenkyū-buntansha)	川崎俊彦近畿大学, 医学部, 講師 (10330268) 地挽隆夫 GE横河メディカル超音波研究室, 室長宗像浩近畿大学, 医学部, 教授 (90111294)
Keywords	肝細胞癌 / dysplastic nodule / 腺腫様過形成 / 早期肝癌 / 血管新生 / 免疫組織染色 / クッパー細胞 / 造影ハーモニックイメージング
Research Abstract	肝細胞癌の発癌・進展においては、門脈血流の関与が極めて重要である。我々は、臨床材料を用いて肝細胞癌の初期病変ならびに前癌病変を門脈造影下CT(CTAP)と血管造影下CT(CTA)を用い、結節の血流動態を詳細に検討した。その結果、前癌病変である過形成結節は動脈血流は乏血性、門脈血流は保たれること、ならびに次のステップの段階では動脈血流も門脈血流も低下した状態に陥ること、さらにはその後、動脈血流が上昇し、多血性となり、通常型肝癌に進展することを本研究により証明した。また、一部の結節は乏血性の結節の中に動脈性血流の増加を認め、nodule in noduleの形をとって最終的に肝細胞癌へ進展することを証明した。また、精密血流画像解析であるCoded Harmonic Angioを用いて検討した結果、このような門脈血流は超音波造影剤Levovistを静注して造影ハーモニック法を行うことにより、明瞭に観察することが可能なことも報告してきた。さらにLevovistは静注後5分後のphaseではKuppfer細胞に貪食、もしくは血管内皮細胞に沈着にするために前癌病変、初期病変では周囲肝と同程度の集積を示し、古典的肝細胞癌では周辺肝に比べて集積が低下することも証明してきた。これは従来より我々がアシアロ糖タンパクレセプターシンチグラフィにより証明したこと、あるいはCTAPで観察してきたこととよく一致する結果である。さらにこのような前癌病変・初期病変のKuppfer細胞をCD68染色で免疫組織染色した結果、前癌病変・初期病変にはCD68陽性細胞が多数存在し、早期肝癌、もしくは中分化型肝癌はCD34陽性の血管新生がおこり始めていることも組織染色により証明した。また、肝細胞癌の初期病変、境界病変が門脈血流と極めて相関し、門脈血流が流入する結節は予後が良いこと、あるいはdoubling timeが長いこと、大型の高分化型肝癌結節はフォローしていても臨床的経過観察をしていても多部位に動脈血流優位の癌が現れやすいことなどを報告した。

Research Products

(36 results)

All Other

All Publications (36 results)

[Publications] Wen YL, Kudo M, Maekawa K, et al.: "Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging : preliminary results in hepatic tumors."J Medical Ultrasonics. 29. 195-204 (2003)
[Publications] Zheng RQ, Kudo M, Inui K, et al.: "Transient portal vein thrombosis caused by radiofrequency ablation for hepatocellular carcinoma."J Gastroenterol. 28. 101-103 (2003)
[Publications] Minami Y, Kudo M, Kawasaki T, et al.: "Transcatheter arterial chemoembolization of hepatocellular carcinoma : usefulness of coded phase-inversion harmonic sonography."AJR. 180. 703-708 (2003)
[Publications] Wen YL, Kudo M, Minami Y, et al.: "Assessment of image quality of contrast-enhanced power Doppler imaging in hepatocellular carcinoma with a personal ultrasound imager : comparison with conventional machine."J Medical Ultrasonics. 30. 31-38 (2003)
[Publications] Kudo M, Chung H, Osaki Y: "Prognostic staging system for hepatocellular carcinoma(CLIP score): value, limitation and a proposal o new prognostic system, Japan Integrated Staging Score(JIS Score)"J Gastroenterol. 38. 207-215 (2003)
[Publications] Kudo M: "Hepatic nodular lesions caused by abnormal hepatic circulation : etiological and clinical aspects."J Gastroenterol. 38. 308-309 (2003)
[Publications] Wen YL, Kudo M, Zheng RQ, et al.: "Spontaneous regurgitation of portal blood flow normalized by meal intake in a patient with alcoholic liver cirrhosis."Hepatol Res. 25. 143-148 (2003)
[Publications] Kawasaki T, Kudo M, Inui K, et al.: "Hepagocellular carcinoma mimicking cavernous hemangioma on angiography and contrast enhanced harmonic ultrasonography. A case report."Hepatol Res. 25. 202-212 (2003)
[Publications] Zheng RQ, Kudo M, Minami Y, et al.: "Stage IV hepatocellular carcinoma with portal venous tumor thrombus : complete response after combined therapy of repeated arterial chemoembolization and radiofreqnency ablation."J Gastroenterol. 38. 406-409 (2003)
[Publications] Kudo M, Minami Y: "Radiofrequency ablation therapy under harmonic imaging guidance for the recurring cancer after local herapy for HCC : a randomized controlled study with RFA under B-mode guidance."Ultrasound Med Biol. 29. 145 (2003)
[Publications] Wen YL, Kudo M, Minami Y, et al.: "Radiofrequency ablation of hepatocellular carcinoma : therapeutic response using contrast-enhanced coded phase-inversion harmonic sonography."AJR. 181. 57-63 (2003)
[Publications] Kudo M: "Contrast harmonic imaging in the diagnosis and treatment of hepatic tumors."Springer Verlag. 1-253 (2003)
[Publications] Wen YL, Kudo M, Minami Y, et al.: "Contrast-enhnaced Agent Detection Imaging : early experience in hepatocellular carcinoma."J Med Ultrasonics. 30. 77-84 (2003)
[Publications] Wen YL, Kudo M, Minami Y, et al.: "Value of new contrast harmonic technique for detecting tumor vascularity in hepatocellular carcinoma : preliminary results."J Medical Ultrasonics. 30. 85-92 (2003)
[Publications] Watanabe T, Kondo M, Kudo M, et al.: "Scintigraphic study of regenerative nodules due to fulminant hepatic failure."J Gastroenterol. 38. 659-699 (2003)
[Publications] Zheng RQ, Chung H, Kudo M: "Hepatobiliary and pancreatic : arterioportal fistula causing portal hypertension."J Gastroenterol Hepatol. 18. 873 (2003)
[Publications] Chung H, Kudo M, Ding H, et al.: "Hepatocellular carcinoma associated with secondary hemochromatosis in non-cirrhotic liver."Hepatol Res. 26. 254-258 (2003)
[Publications] Wen YL, Kudo M, Minami Y, et al.: "Detection of tumor vascularity in hepatocellular carcinoma with contrast enhanced Dynamic Flow imaging : comparison with contrast enhanced power Doppler imaging."J Medical Ultrasonics. 30. 141-151 (2003)
[Publications] Chung H, Kudo M, Kumada T, et al.: "Risk of HCV transmission after needlestick accident and the efficacy of short duration interferon treatment to prevent HCV transmission to medical personnel."J Gastroenterol. 38. 877-879 (2003)
[Publications] Minami Y, Kudo M, Kawasaki T, et al.: "Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome."J Gastroenterol. 38. 1066-1070 (2003)
[Publications] Zheng RQ, Kudo M: "Hepatobiliary and pancreatic : fatty liver, spared areas and aberrant gastric venous drainage."J Gastroenterol Hepatol. 18. 1423 (2003)
[Publications] Zheng RQ, Kudo M: "Characterization of hepatic tumors : value of contrast-enhanced coded phase inversion harmonic US."AJR. (in press). (2004)
[Publications] Zheng RQ, Kudo M: "Hyperplastic nodules in cirrhosis."J Gastroenterol Hepatol. (in press). (2004)
[Publications] Kitano M, Kudo M, Maekawa K, et al.: "Dynamic imaging of pancreatic diseases by contrast-enhanced coded phase-inversion harmonic US."Gut. (in press). (2004)
[Publications] Kawasaki T, Kudo M, Chung H, et al.: "Hepatocellular carcinoma ruptured during radiofrequency ablation therapy."J Gastroenterol. (in press). (2004)
[Publications] Kudo M: "Local ablation therapy for hepatocellular carcinoma : current status and future perspective."J Gastroenterol. (in press). (2004)
[Publications] Kudo M: "Hepatocellular carcinoma and NASH."J Gastroenterol. (in press). (2004)
[Publications] Wen YL, Kudo M: "Detection of the intratumoral vascularity in small hepatocellular carcinoma by coded phase inversion harmonic US."Intervirology. (in press). (2004)
[Publications] Kudo M: "Large atypical benign-nature hepatocellular carcinoma : a new clinical entity."Intervirology. (in press). (2004)
[Publications] Kudo M, Tochio H: "Differentiation of hepatic tumors by color Doppler imaging : role of the maximum velocity and the pulsatility index of intratumoral blood flow signal."Intervirology. (in press). (2004)
[Publications] Zheng RQ, Kudo M: "Hepatocellular carcinoma with nodule in nodule appearance : imaging by contrast-enhanced coded phase-inversion harmonic US."Intervirology. (in press). (2004)
[Publications] Tochio H, Kudo M: "Afferent and efferent vessel of premalignant and overt HCC : Observation by color Doppler imaging."Intervirology. (in press). (2004)
[Publications] Matsui S, Kudo M, Nakaoka R, et al.: "Comparison of argon plasma coagulation and paravariceal injection sclerotherapy of 1% polidocanol in the mucosa-fibrosing therapy for esophageal varices."J Gastroenterol 2003. (in press). (2004)
[Publications] Kim SR, Maekawa Y, Kudo M, et al.: "Hypervascular liver nodules in heavy drinkers of alcohol."Alcoholism : Clinical and Experimental Research 2004. (in press). (2004)
[Publications] Minami Y, Kudo M, Kawasaki T, et al.: "Radiofrequency ablation for sonography undetectable hepatocellular carcinoma in the hepatic dome : value of cntrast-enhanced harmonic sonography associated with artificial pleural effusion."AJR. (in press). (2004)
[Publications] Kudo M: "A new prognostic staging system for hepatocellular carcinoma, the Japan Integrated Staging Score(JIS Score)."Intervirology review article. (in press). (2004)

2003 Fiscal Year Annual Research Report

肝細胞癌の発癌・進展における腫瘍血管構築の精密血流画像解析とその分子機構の解明

Principal Investigator

工藤 正俊 近畿大学, 医学部, 教授 (10298953)

Research Products

[Publications] Wen YL, Kudo M, Maekawa K, et al.: "Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging : preliminary results in hepatic tumors."J Medical Ultrasonics. 29. 195-204 (2003)

[Publications] Zheng RQ, Kudo M, Inui K, et al.: "Transient portal vein thrombosis caused by radiofrequency ablation for hepatocellular carcinoma."J Gastroenterol. 28. 101-103 (2003)

[Publications] Minami Y, Kudo M, Kawasaki T, et al.: "Transcatheter arterial chemoembolization of hepatocellular carcinoma : usefulness of coded phase-inversion harmonic sonography."AJR. 180. 703-708 (2003)

[Publications] Wen YL, Kudo M, Minami Y, et al.: "Assessment of image quality of contrast-enhanced power Doppler imaging in hepatocellular carcinoma with a personal ultrasound imager : comparison with conventional machine."J Medical Ultrasonics. 30. 31-38 (2003)

[Publications] Kudo M, Chung H, Osaki Y: "Prognostic staging system for hepatocellular carcinoma(CLIP score): value, limitation and a proposal o new prognostic system, Japan Integrated Staging Score(JIS Score)"J Gastroenterol. 38. 207-215 (2003)

[Publications] Kudo M: "Hepatic nodular lesions caused by abnormal hepatic circulation : etiological and clinical aspects."J Gastroenterol. 38. 308-309 (2003)

[Publications] Wen YL, Kudo M, Zheng RQ, et al.: "Spontaneous regurgitation of portal blood flow normalized by meal intake in a patient with alcoholic liver cirrhosis."Hepatol Res. 25. 143-148 (2003)

[Publications] Kawasaki T, Kudo M, Inui K, et al.: "Hepagocellular carcinoma mimicking cavernous hemangioma on angiography and contrast enhanced harmonic ultrasonography. A case report."Hepatol Res. 25. 202-212 (2003)

[Publications] Zheng RQ, Kudo M, Minami Y, et al.: "Stage IV hepatocellular carcinoma with portal venous tumor thrombus : complete response after combined therapy of repeated arterial chemoembolization and radiofreqnency ablation."J Gastroenterol. 38. 406-409 (2003)

[Publications] Kudo M, Minami Y: "Radiofrequency ablation therapy under harmonic imaging guidance for the recurring cancer after local herapy for HCC : a randomized controlled study with RFA under B-mode guidance."Ultrasound Med Biol. 29. 145 (2003)

[Publications] Wen YL, Kudo M, Minami Y, et al.: "Radiofrequency ablation of hepatocellular carcinoma : therapeutic response using contrast-enhanced coded phase-inversion harmonic sonography."AJR. 181. 57-63 (2003)

[Publications] Kudo M: "Contrast harmonic imaging in the diagnosis and treatment of hepatic tumors."Springer Verlag. 1-253 (2003)

[Publications] Wen YL, Kudo M, Minami Y, et al.: "Contrast-enhnaced Agent Detection Imaging : early experience in hepatocellular carcinoma."J Med Ultrasonics. 30. 77-84 (2003)

[Publications] Wen YL, Kudo M, Minami Y, et al.: "Value of new contrast harmonic technique for detecting tumor vascularity in hepatocellular carcinoma : preliminary results."J Medical Ultrasonics. 30. 85-92 (2003)

[Publications] Watanabe T, Kondo M, Kudo M, et al.: "Scintigraphic study of regenerative nodules due to fulminant hepatic failure."J Gastroenterol. 38. 659-699 (2003)

[Publications] Zheng RQ, Chung H, Kudo M: "Hepatobiliary and pancreatic : arterioportal fistula causing portal hypertension."J Gastroenterol Hepatol. 18. 873 (2003)

[Publications] Chung H, Kudo M, Ding H, et al.: "Hepatocellular carcinoma associated with secondary hemochromatosis in non-cirrhotic liver."Hepatol Res. 26. 254-258 (2003)

[Publications] Wen YL, Kudo M, Minami Y, et al.: "Detection of tumor vascularity in hepatocellular carcinoma with contrast enhanced Dynamic Flow imaging : comparison with contrast enhanced power Doppler imaging."J Medical Ultrasonics. 30. 141-151 (2003)

[Publications] Chung H, Kudo M, Kumada T, et al.: "Risk of HCV transmission after needlestick accident and the efficacy of short duration interferon treatment to prevent HCV transmission to medical personnel."J Gastroenterol. 38. 877-879 (2003)

[Publications] Minami Y, Kudo M, Kawasaki T, et al.: "Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome."J Gastroenterol. 38. 1066-1070 (2003)

[Publications] Zheng RQ, Kudo M: "Hepatobiliary and pancreatic : fatty liver, spared areas and aberrant gastric venous drainage."J Gastroenterol Hepatol. 18. 1423 (2003)

[Publications] Zheng RQ, Kudo M: "Characterization of hepatic tumors : value of contrast-enhanced coded phase inversion harmonic US."AJR. (in press). (2004)

[Publications] Zheng RQ, Kudo M: "Hyperplastic nodules in cirrhosis."J Gastroenterol Hepatol. (in press). (2004)

[Publications] Kitano M, Kudo M, Maekawa K, et al.: "Dynamic imaging of pancreatic diseases by contrast-enhanced coded phase-inversion harmonic US."Gut. (in press). (2004)

[Publications] Kawasaki T, Kudo M, Chung H, et al.: "Hepatocellular carcinoma ruptured during radiofrequency ablation therapy."J Gastroenterol. (in press). (2004)

[Publications] Kudo M: "Local ablation therapy for hepatocellular carcinoma : current status and future perspective."J Gastroenterol. (in press). (2004)

[Publications] Kudo M: "Hepatocellular carcinoma and NASH."J Gastroenterol. (in press). (2004)

[Publications] Wen YL, Kudo M: "Detection of the intratumoral vascularity in small hepatocellular carcinoma by coded phase inversion harmonic US."Intervirology. (in press). (2004)

[Publications] Kudo M: "Large atypical benign-nature hepatocellular carcinoma : a new clinical entity."Intervirology. (in press). (2004)

[Publications] Kudo M, Tochio H: "Differentiation of hepatic tumors by color Doppler imaging : role of the maximum velocity and the pulsatility index of intratumoral blood flow signal."Intervirology. (in press). (2004)

[Publications] Zheng RQ, Kudo M: "Hepatocellular carcinoma with nodule in nodule appearance : imaging by contrast-enhanced coded phase-inversion harmonic US."Intervirology. (in press). (2004)

[Publications] Tochio H, Kudo M: "Afferent and efferent vessel of premalignant and overt HCC : Observation by color Doppler imaging."Intervirology. (in press). (2004)

[Publications] Matsui S, Kudo M, Nakaoka R, et al.: "Comparison of argon plasma coagulation and paravariceal injection sclerotherapy of 1% polidocanol in the mucosa-fibrosing therapy for esophageal varices."J Gastroenterol 2003. (in press). (2004)

[Publications] Kim SR, Maekawa Y, Kudo M, et al.: "Hypervascular liver nodules in heavy drinkers of alcohol."Alcoholism : Clinical and Experimental Research 2004. (in press). (2004)

[Publications] Minami Y, Kudo M, Kawasaki T, et al.: "Radiofrequency ablation for sonography undetectable hepatocellular carcinoma in the hepatic dome : value of cntrast-enhanced harmonic sonography associated with artificial pleural effusion."AJR. (in press). (2004)

[Publications] Kudo M: "A new prognostic staging system for hepatocellular carcinoma, the Japan Integrated Staging Score(JIS Score)."Intervirology review article. (in press). (2004)

工藤正俊近畿大学, 医学部, 教授 (10298953)