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Published in: Journal of Cancer Research and Clinical Oncology 4/2011

01-04-2011 | Original Paper

Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior

Authors: Xin-Yuan Lu, Tao Xi, Wan-Yee Lau, Hui Dong, Zhi-Hong Xian, Hua Yu, Zhen Zhu, Feng Shen, Meng-Chao Wu, Wen-Ming Cong

Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2011

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Abstract

Purpose

Increasing evidence has suggested that tumor size is one of the independent prognostic factors of patients with hepatocellular carcinoma (HCC). However, the criteria used to determine when HCC should be classified as small remain controversial. Our objective was to evaluate the relationship between the size of HCC and its clinicopathological features.

Methods

A retrospective study on 618 patients who underwent partial hepatectomy for solitary HCC was performed. These patients were divided into Groups 1–5 according to the tumor diameter: ≤1, 1.1–2, 2.1–3, 3.1–5 and >5 cm, respectively. The clinicopathological variables of the patients in each group were compared statistically.

Results

Except for the microHCC (≤1 cm) which differed significantly from the other four groups in the clinicopathological variables, almost no differences existed among HCC ranging from 1 to 3 cm, or HCCs > 3 cm. If ≤3 cm was used as the cut-off point for small HCC (SHCC), and >3 cm for large HCC (LHCC), significant differences (P < 0.05–0.01) were observed between SHCC and LHCC in: histological grades I–II (48.0 vs. 19.4 %), capsular invasion (15.4 vs. 36.3%), tumor thrombi (6.9 vs. 23.5%), satellite nodules (12.3 vs. 35.5%), noninvasive growth patterns (69.6 vs. 25.4%), the overall survival (OS, 119.6 ± 34.7 vs. 68.5 ± 6.6 months), and the recurrence-free survival (RFS, 67.0 ± 16.7 vs. 29.5 ± 3.2 months). Multivariate Cox regression analyses show that tumor size >3 cm was one of the independent prognostic factors for both OS and RFS.

Conclusions

The 3 cm cutoff seems to best determine the biological behavior and clinical prognosis of patients undergoing partial hepatectomy for early stage HCC. Overall, HCC smaller than 3 cm in diameter was closely related with a better prognosis which reflected the relatively benign pathobiological features at an early developmental stage. As HCC > 3 cm exhibited a tendency towards more aggressive behavior, we suggest that HCC ≤ 3 cm in diameter should be used as a critical size of SHCC at which curative treatment achieves better long-term survivals.
Literature
go back to reference Aishima S, Nishihara Y, Kuroda Y, Taguchi K, Iguchi T, Taketomi A et al (2007) Histologic characteristics and prognostic significance in small hepatocellular carcinoma with biliary differentiation: subdivision and comparison with ordinary hepatocellular carcinoma. Am J Surg Pathol 31:783–791PubMedCrossRef Aishima S, Nishihara Y, Kuroda Y, Taguchi K, Iguchi T, Taketomi A et al (2007) Histologic characteristics and prognostic significance in small hepatocellular carcinoma with biliary differentiation: subdivision and comparison with ordinary hepatocellular carcinoma. Am J Surg Pathol 31:783–791PubMedCrossRef
go back to reference Arii S, Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M et al (2000) Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 32:1224–1229PubMedCrossRef Arii S, Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M et al (2000) Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 32:1224–1229PubMedCrossRef
go back to reference Chung H, Kudo M, Takahashi S, Hagiwara S, Sakaguchi Y, Inoue T et al (2008) Comparison of three current staging systems for hepatocellular carcinoma: Japan integrated staging score, new Barcelona Clinic Liver Cancer staging classification, and Tokyo score. J Gastroenterol Hepatol 23:445–452PubMedCrossRef Chung H, Kudo M, Takahashi S, Hagiwara S, Sakaguchi Y, Inoue T et al (2008) Comparison of three current staging systems for hepatocellular carcinoma: Japan integrated staging score, new Barcelona Clinic Liver Cancer staging classification, and Tokyo score. J Gastroenterol Hepatol 23:445–452PubMedCrossRef
go back to reference Cong WM, Wu MC (1990) The biopathologic characteristics of DNA content of hepatocellular carcinomas. Cancer 66:498–501PubMedCrossRef Cong WM, Wu MC (1990) The biopathologic characteristics of DNA content of hepatocellular carcinomas. Cancer 66:498–501PubMedCrossRef
go back to reference Cong WM, Wu MC, Zhang XZ (1992) Characteristic changes of DNA stemlines during hepatocarcinogenesis in rats. Chin Med J 105:535–538PubMed Cong WM, Wu MC, Zhang XZ (1992) Characteristic changes of DNA stemlines during hepatocarcinogenesis in rats. Chin Med J 105:535–538PubMed
go back to reference Cong WM, Wu MC, Wang Y, Zhang XZ, Chen H (1997) Primary liver tumors in China: a surgicopathological study of 3, 160 cases. Oncol Rep 4:649–652 Cong WM, Wu MC, Wang Y, Zhang XZ, Chen H (1997) Primary liver tumors in China: a surgicopathological study of 3, 160 cases. Oncol Rep 4:649–652
go back to reference Farinati F, Sergio A, Baldan A, Giacomin A, Di Nolfo MA, Del Poggio P et al (2009) Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study. BMC Cancer 9:33PubMedCrossRef Farinati F, Sergio A, Baldan A, Giacomin A, Di Nolfo MA, Del Poggio P et al (2009) Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study. BMC Cancer 9:33PubMedCrossRef
go back to reference Forner A, Vilana R, Ayuso C, Bianchi L, Sole M, Ayuso JR et al (2008) Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 47:97–104PubMedCrossRef Forner A, Vilana R, Ayuso C, Bianchi L, Sole M, Ayuso JR et al (2008) Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 47:97–104PubMedCrossRef
go back to reference Gospodarowicz MK, Cazap E, Jadad AR (2009) Cancer in the world—a call for international collaboration. Salud pública Méx 51:305–308CrossRef Gospodarowicz MK, Cazap E, Jadad AR (2009) Cancer in the world—a call for international collaboration. Salud pública Méx 51:305–308CrossRef
go back to reference Hamilton SR, Aaltonen LA (2000) World Health Organization Classification of tumours: pathology and genetics of tumours of the digestive system. IARC, Lyon Hamilton SR, Aaltonen LA (2000) World Health Organization Classification of tumours: pathology and genetics of tumours of the digestive system. IARC, Lyon
go back to reference International Consensus Group for Hepatocellular Neoplasia (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 49:658–664CrossRef International Consensus Group for Hepatocellular Neoplasia (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 49:658–664CrossRef
go back to reference Kanematsu T, Sonoda T, Takenaka K, Matsumata T, Sugimachi K, Inokuchi K (1985) The value of ultrasound in the diagnosis and treatment of small hepatocellular carcinoma. Br J Surg 72:23–25PubMedCrossRef Kanematsu T, Sonoda T, Takenaka K, Matsumata T, Sugimachi K, Inokuchi K (1985) The value of ultrasound in the diagnosis and treatment of small hepatocellular carcinoma. Br J Surg 72:23–25PubMedCrossRef
go back to reference Kojiro M, Nakashima O (1999) Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumors. Semin Liver Dis 19:287–296PubMedCrossRef Kojiro M, Nakashima O (1999) Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumors. Semin Liver Dis 19:287–296PubMedCrossRef
go back to reference Kondo Y, Niwa Y, Akikusa B, Takazawa H, Okabayashi A (1983) A histopathologic study of early hepatocellular carcinoma. Cancer 52:687–692PubMedCrossRef Kondo Y, Niwa Y, Akikusa B, Takazawa H, Okabayashi A (1983) A histopathologic study of early hepatocellular carcinoma. Cancer 52:687–692PubMedCrossRef
go back to reference Kudo M (2004) Atypical large well-differentiated hepatocellular carcinoma with benign nature: a new clinical entity. Intervirology 47:227–237PubMedCrossRef Kudo M (2004) Atypical large well-differentiated hepatocellular carcinoma with benign nature: a new clinical entity. Intervirology 47:227–237PubMedCrossRef
go back to reference Kunisaki C, Makino H, Takagawa R, Oshima T, Nagano Y, Kosaka T et al (2008) Tumor diameter as a prognostic factor in patients with gastric cancer. Ann Surg Oncol 15:1959–1967PubMedCrossRef Kunisaki C, Makino H, Takagawa R, Oshima T, Nagano Y, Kosaka T et al (2008) Tumor diameter as a prognostic factor in patients with gastric cancer. Ann Surg Oncol 15:1959–1967PubMedCrossRef
go back to reference Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, Nevens F et al (2006) Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 30:1405–1411PubMedCrossRef Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, Nevens F et al (2006) Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 30:1405–1411PubMedCrossRef
go back to reference Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338PubMedCrossRef Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338PubMedCrossRef
go back to reference Llovet JM, Fuster J, Bruix J (2004) The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 10:S115–S120PubMedCrossRef Llovet JM, Fuster J, Bruix J (2004) The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 10:S115–S120PubMedCrossRef
go back to reference Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M (2007) Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg 245:909–922PubMedCrossRef Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M (2007) Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg 245:909–922PubMedCrossRef
go back to reference Moribe T, Iizuka N, Miura T, Kimura N, Tamatsukuri S, Ishitsuka H et al (2009) Methylation of multiple genes as molecular markers for diagnosis of a small, well-differentiated hepatocellular carcinoma. Int J Cancer 125:388–397PubMedCrossRef Moribe T, Iizuka N, Miura T, Kimura N, Tamatsukuri S, Ishitsuka H et al (2009) Methylation of multiple genes as molecular markers for diagnosis of a small, well-differentiated hepatocellular carcinoma. Int J Cancer 125:388–397PubMedCrossRef
go back to reference Nagao T, Nagashima I, Inoue S, Omori Y, Kawano N, Morioka Y (1992) Hepatic resection for minute hepatocellular carcinoma. Surg Today 22:110–114PubMedCrossRef Nagao T, Nagashima I, Inoue S, Omori Y, Kawano N, Morioka Y (1992) Hepatic resection for minute hepatocellular carcinoma. Surg Today 22:110–114PubMedCrossRef
go back to reference Okuda K, Nakashima T, Obata H, Kubo Y (1977) Clinicopathological studies of minute hepatocellular carcinoma. Analysis of 20 cases, including 4 with hepatic resection. Gastroenterology 73:109–115PubMed Okuda K, Nakashima T, Obata H, Kubo Y (1977) Clinicopathological studies of minute hepatocellular carcinoma. Analysis of 20 cases, including 4 with hepatic resection. Gastroenterology 73:109–115PubMed
go back to reference Okuwaki Y, Nakazawa T, Shibuya A, Ono K, Hidaka H, Watanabe M et al (2008) Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: risk factors and patterns. J Gastroenterol 43:71–78PubMedCrossRef Okuwaki Y, Nakazawa T, Shibuya A, Ono K, Hidaka H, Watanabe M et al (2008) Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: risk factors and patterns. J Gastroenterol 43:71–78PubMedCrossRef
go back to reference Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I et al (2005) Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 11:1086–1092PubMedCrossRef Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I et al (2005) Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 11:1086–1092PubMedCrossRef
go back to reference Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH et al (2006) Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol 132:458–465PubMedCrossRef Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH et al (2006) Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol 132:458–465PubMedCrossRef
go back to reference Tang Z, Yeqin Y, Zhiying L, Xinda Z, Binghui Y, Yunzhen C et al (1979) Small hepatocellular carcinoma: clinical analysis of 30 cases. Chin Med J 92:455–462 Tang Z, Yeqin Y, Zhiying L, Xinda Z, Binghui Y, Yunzhen C et al (1979) Small hepatocellular carcinoma: clinical analysis of 30 cases. Chin Med J 92:455–462
go back to reference Tang Z, Yeqin Y, Zhou XD, Ma ZC, Yang R, Lu JZ (1989) Surgery of small hepatocellular carcinoma. Analysis of 144 cases. Cancer 64:536–541 Tang Z, Yeqin Y, Zhou XD, Ma ZC, Yang R, Lu JZ (1989) Surgery of small hepatocellular carcinoma. Analysis of 144 cases. Cancer 64:536–541
go back to reference Ueno S, Kubo F, Sakoda M, Hiwatashi K, Tateno T, Mataki Y et al (2008) Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification. J Hepatobiliary Pancreat 15:493–500CrossRef Ueno S, Kubo F, Sakoda M, Hiwatashi K, Tateno T, Mataki Y et al (2008) Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification. J Hepatobiliary Pancreat 15:493–500CrossRef
go back to reference Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N et al (2002) Simplified staging for hepatocellular carcinoma. J Clin Oncol 20:1527–1536PubMedCrossRef Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N et al (2002) Simplified staging for hepatocellular carcinoma. J Clin Oncol 20:1527–1536PubMedCrossRef
go back to reference Wu MC, Chen H, Zhang XH, Yao XP, Yang JM (1980) Primary hepatic carcinoma resection over 18 years. Chin Med J 93:723–728PubMed Wu MC, Chen H, Zhang XH, Yao XP, Yang JM (1980) Primary hepatic carcinoma resection over 18 years. Chin Med J 93:723–728PubMed
Metadata
Title
Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior
Authors
Xin-Yuan Lu
Tao Xi
Wan-Yee Lau
Hui Dong
Zhi-Hong Xian
Hua Yu
Zhen Zhu
Feng Shen
Meng-Chao Wu
Wen-Ming Cong
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 4/2011
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0909-5

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