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Published in: Journal of Gastrointestinal Surgery 6/2017

01-06-2017 | Original Article

Double- and Triple-Positive Tumor Markers Predict Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh Class A

Authors: Tomoki Ryu, Yuko Takami, Yoshiyuki Wada, Masaki Tateishi, Hajime Matsushima, Kazuhiro Mikagi, Hideki Saitsu

Published in: Journal of Gastrointestinal Surgery | Issue 6/2017

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Abstract

The prognostic implications of the expression patterns of three tumor markers, alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxy prothrombin (DCP), have been evaluated in patients with hepatocellular carcinoma (HCC). From January 1994 to December 2014, 1182 consecutive patients underwent hepatic resection and surgical microwave ablation for HCC at our institution. This study analyzed 475 patients within the Milan criteria and Child–Pugh class A. Cumulative overall survival (OS) and disease-free survival (DFS) rates were analyzed relative to the number of positive tumor markers. OS and DFS at 5 years postoperatively were 85.3 and 44.2% in triple-negative patients, 79.4 and 48.0% in single-positive patients, 56.2 and 32.9% in double-positive patients, and 61.7 and 35.7% in triple-positive patients with statistical significance. OS in triple-negative or single-positive patients was 85.3%, and that in all double- or triple-positive patients was 58.0% (P < 0.0001); DFS at 5 years postoperatively in these two groups was 45.9 and 34.0%, respectively (P < 0.0013). Both double- and triple-positive tumor markers are associated with early recurrence and poor survival in HCC patients within the Milan criteria and Child–Pugh class A.
Literature
1.
go back to reference Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–2150.CrossRefPubMed Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–2150.CrossRefPubMed
2.
go back to reference Taura N, Fukushima N, Yastuhashi H, Takami Y, Seike M, Watanabe H, Mizuta T, Sasaki Y, Nagata K, Tabara A, Komorizono Y, Taketomi A, Matsumoto S, Tamai T, Muro T, Nakao K, Fukuizumi K, Maeshiro T, Inoue O, Sata M. The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area. Med Sci Monit. 2011;17:PH7–11.CrossRefPubMedPubMedCentral Taura N, Fukushima N, Yastuhashi H, Takami Y, Seike M, Watanabe H, Mizuta T, Sasaki Y, Nagata K, Tabara A, Komorizono Y, Taketomi A, Matsumoto S, Tamai T, Muro T, Nakao K, Fukuizumi K, Maeshiro T, Inoue O, Sata M. The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area. Med Sci Monit. 2011;17:PH7–11.CrossRefPubMedPubMedCentral
3.
go back to reference Mazzaferro V, Regalia E, Doci R, Andrela S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;344:693–700.CrossRef Mazzaferro V, Regalia E, Doci R, Andrela S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;344:693–700.CrossRef
4.
go back to reference Kamiyama T, Nakanishi K, Yokoo H, Kamachi H, Tahara M, Suzuki T, Shimamura T, Furukawa H, Matsushita M, Todo S. Recurrence patterns after hepatectomy of hepatocellular carcinoma: implication of Milan criteria utilization. Ann Surg Oncol. 2009;16:1560–1571.CrossRefPubMed Kamiyama T, Nakanishi K, Yokoo H, Kamachi H, Tahara M, Suzuki T, Shimamura T, Furukawa H, Matsushita M, Todo S. Recurrence patterns after hepatectomy of hepatocellular carcinoma: implication of Milan criteria utilization. Ann Surg Oncol. 2009;16:1560–1571.CrossRefPubMed
5.
go back to reference Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Nakamura S, Konno H. Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for hepatocellular carcinoma meeting the Milan criteria. Surg Today. 2010;40:638–645.CrossRefPubMed Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Nakamura S, Konno H. Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for hepatocellular carcinoma meeting the Milan criteria. Surg Today. 2010;40:638–645.CrossRefPubMed
6.
go back to reference Kumada T, Nakano S, Takeda I, Kiriyama S, Sone Y, Hayashi K, Katoh H, Endoh T, Sassa T, Satomura S. Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis. J Hepatol. 1999;30:125–130.CrossRefPubMed Kumada T, Nakano S, Takeda I, Kiriyama S, Sone Y, Hayashi K, Katoh H, Endoh T, Sassa T, Satomura S. Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis. J Hepatol. 1999;30:125–130.CrossRefPubMed
7.
go back to reference Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, Yoshida H, Shiina S, Omata M. Des-γ-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer. 2001;91:561–569.CrossRefPubMed Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, Yoshida H, Shiina S, Omata M. Des-γ-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer. 2001;91:561–569.CrossRefPubMed
8.
go back to reference Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Yamaguchi M, Kaneoka Y, Washizu J. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006;4:111–117.CrossRefPubMed Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Yamaguchi M, Kaneoka Y, Washizu J. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006;4:111–117.CrossRefPubMed
9.
go back to reference Kiriyama S, Uchiyama K, Ueno M, Ozawa S, Hayami S, Tani M, Yamaue H. Triple positive tumor markers for hepatocellular carcinoma are useful predictors of poor survival. Ann Surg. 2011;254:984–991.CrossRefPubMed Kiriyama S, Uchiyama K, Ueno M, Ozawa S, Hayami S, Tani M, Yamaue H. Triple positive tumor markers for hepatocellular carcinoma are useful predictors of poor survival. Ann Surg. 2011;254:984–991.CrossRefPubMed
10.
go back to reference Nakagawa S, Beppu T, Okabe H, Okabe H, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Hayashi H, Sakamoto Y, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Baba H. Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma. Hepatol Res. 2014;44:964–974.CrossRefPubMed Nakagawa S, Beppu T, Okabe H, Okabe H, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Hayashi H, Sakamoto Y, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Baba H. Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma. Hepatol Res. 2014;44:964–974.CrossRefPubMed
11.
go back to reference Takami Y, Ryu T, Wada Y, Saitsu H. Evaluation of intraoperative microwave coagulo-necrotic therapy (MCN) for hepatocellular carcinoma: a single center experience of 719 consecutive cases. J Hepatobiliary Pancreat Sci. 2013;20:332–341.CrossRefPubMed Takami Y, Ryu T, Wada Y, Saitsu H. Evaluation of intraoperative microwave coagulo-necrotic therapy (MCN) for hepatocellular carcinoma: a single center experience of 719 consecutive cases. J Hepatobiliary Pancreat Sci. 2013;20:332–341.CrossRefPubMed
12.
go back to reference Ryu T, Takami Y, Tsutsumi N, Tateishi M, Mikagi K, Wada Y, Saitsu H. Simultaneous microwave coagulo-necrotic therapy (MCN) and laparoscopic splenectomy for the treatment of hepatocellular carcinoma with cirrhotic hypersplenism. Surg Today. 2016; doi: 10.1007/s00595-016-1411-1418. Ryu T, Takami Y, Tsutsumi N, Tateishi M, Mikagi K, Wada Y, Saitsu H. Simultaneous microwave coagulo-necrotic therapy (MCN) and laparoscopic splenectomy for the treatment of hepatocellular carcinoma with cirrhotic hypersplenism. Surg Today. 2016; doi: 10.​1007/​s00595-016-1411-1418.
13.
go back to reference Wada Y, Takami Y, Tateishi M, Ryu T, Mikagi K, Saitsu H. Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases. OncoTargets Ther. 2016;9:937–943.CrossRef Wada Y, Takami Y, Tateishi M, Ryu T, Mikagi K, Saitsu H. Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases. OncoTargets Ther. 2016;9:937–943.CrossRef
14.
go back to reference Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649.CrossRefPubMed Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649.CrossRefPubMed
15.
go back to reference Liver Cancer Study Group of Japan. General rules for the clinical and pathological study of primary liver cancer, 3rd English edn. Tokyo: Kanehara Shuppan, 2010. Liver Cancer Study Group of Japan. General rules for the clinical and pathological study of primary liver cancer, 3rd English edn. Tokyo: Kanehara Shuppan, 2010.
16.
go back to reference Tateyama M, Yatsuhashi H, Taura N, Motoyoshi Y, Nagaoka S, Yanagi K, Abiru S, Yano K, Komori A, Migita K, Nakamura M, Nagahara H, Sasaki Y, Miyakawa Y, Ishibashi H. Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 2011;46:92–100.CrossRefPubMed Tateyama M, Yatsuhashi H, Taura N, Motoyoshi Y, Nagaoka S, Yanagi K, Abiru S, Yano K, Komori A, Migita K, Nakamura M, Nagahara H, Sasaki Y, Miyakawa Y, Ishibashi H. Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 2011;46:92–100.CrossRefPubMed
17.
go back to reference Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, Rapaccini G, Del Poggio P, Di Nolfo MA, Benvegnu L, Zoli M, Borzio F, Bernardi M, Trevisani F. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither. Am J Gastroenterol 2006;101:524–532.CrossRefPubMed Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, Rapaccini G, Del Poggio P, Di Nolfo MA, Benvegnu L, Zoli M, Borzio F, Bernardi M, Trevisani F. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither. Am J Gastroenterol 2006;101:524–532.CrossRefPubMed
18.
go back to reference Kobayashi M, Hosaka T, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Saitoh S, Arase Y, Kumada H. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre- and postoperatively. Hepatol Res 2011;41:1036–1045.CrossRefPubMed Kobayashi M, Hosaka T, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Saitoh S, Arase Y, Kumada H. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre- and postoperatively. Hepatol Res 2011;41:1036–1045.CrossRefPubMed
19.
go back to reference Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S. Early hepatocellular carcinoma as an entity with a high cure rate of surgical cure. Hepatology. 1998;28:1241–1246.CrossRefPubMed Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S. Early hepatocellular carcinoma as an entity with a high cure rate of surgical cure. Hepatology. 1998;28:1241–1246.CrossRefPubMed
20.
go back to reference Belghiti J, Hiramatsu K, Benoist S, Massault PP, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 2000;191:38–46.CrossRefPubMed Belghiti J, Hiramatsu K, Benoist S, Massault PP, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 2000;191:38–46.CrossRefPubMed
21.
22.
go back to reference Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;103:1201–1209.CrossRefPubMed Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;103:1201–1209.CrossRefPubMed
23.
go back to reference Saitsu H, Yoshida M, Taniwaki S, Sato H, Okami N, Matsumoto A, Shigetomi K, Sugiyama T, Okuda Y, Nakayama K. Laparoscopic coagulo-necrotic therapy using microtase for small hepatocellular carcinoma. Jpn J Gastroenterol. 1991;88:2727. Saitsu H, Yoshida M, Taniwaki S, Sato H, Okami N, Matsumoto A, Shigetomi K, Sugiyama T, Okuda Y, Nakayama K. Laparoscopic coagulo-necrotic therapy using microtase for small hepatocellular carcinoma. Jpn J Gastroenterol. 1991;88:2727.
24.
go back to reference Takenaka K, Kawahara N, Yamamoto K, Kajiyama K, Maeda T, Itasaka H, Shirabe K, Nishizaki T, Yanaga K, Sugimachi K. Results of 280 liver resections for hepatocellular carcinoma. Arch Surg 1996;131:71–76.CrossRefPubMed Takenaka K, Kawahara N, Yamamoto K, Kajiyama K, Maeda T, Itasaka H, Shirabe K, Nishizaki T, Yanaga K, Sugimachi K. Results of 280 liver resections for hepatocellular carcinoma. Arch Surg 1996;131:71–76.CrossRefPubMed
25.
go back to reference Kobayashi A, Miyagawa S, Miwa S, Nakata T. Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2008;15:515–1521.CrossRefPubMed Kobayashi A, Miyagawa S, Miwa S, Nakata T. Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2008;15:515–1521.CrossRefPubMed
26.
go back to reference Yamamoto J, Kosuge T, Takayama T, Shimada K, Yamasaki S, Ozaki H, Yamaguchi N, Makuuchi M. Recurrence of hepatocellular carcinoma after surgery. Br J Surg 1996;83:1219–1222.CrossRefPubMed Yamamoto J, Kosuge T, Takayama T, Shimada K, Yamasaki S, Ozaki H, Yamaguchi N, Makuuchi M. Recurrence of hepatocellular carcinoma after surgery. Br J Surg 1996;83:1219–1222.CrossRefPubMed
Metadata
Title
Double- and Triple-Positive Tumor Markers Predict Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh Class A
Authors
Tomoki Ryu
Yuko Takami
Yoshiyuki Wada
Masaki Tateishi
Hajime Matsushima
Kazuhiro Mikagi
Hideki Saitsu
Publication date
01-06-2017
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 6/2017
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-017-3394-1

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