Abstract
Background
Hepatocellular carcinoma (HCC) ≤2 cm in diameter is considered to have a low potential for malignancy.
Methods
A retrospective review was undertaken of 149 patients with primary solitary HCC ≤2 cm who underwent initial hepatic resection between 1994 and 2010. The independent predictors of the microinvasion (MI) such as portal venous, hepatic vein, or bile duct infiltration and/or intrahepatic metastasis were identified by multivariate analysis. Prognosis of patients with HCC ≤2 cm accompanied by MI was compared to that of patients with HCC ≤2 cm without MI.
Results
Forty-three patients with HCC ≤2 cm had MI in patients (28.9%). Three independent predictors of the MI were revealed: invasive gross type (simple nodular type with extranodular growth or confluent multinodular type), des-γ-carboxy prothrombin (DCP) >100 mAU/ml, and poorly differentiated. Disease-free survival rates of patients with HCC ≤2 cm with MI (3 year 44%) were significantly worse than those for HCC ≤2 cm without MI (3 year 72%). This disadvantage of disease-free survival rate of patients with HCC ≤2 cm with MI could be dissolved by hepatic resection with a wide tumor margin of ≥5 mm (P = 0.04).
Conclusions
Even in cases of HCC ≤2 cm, patients who are suspected of having invasive gross type tumors in preoperative imaging diagnosis or who have a high DCP level (>100 mAU/ml) are at risk for MI. Therefore, in such patients, hepatic resection with a wide tumor margin should be recommended.
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References
Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl. 2005;11:1086–92.
Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol. 1991;22:172–8.
Liver Cancer Study Group of Japan. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Ann Surg. 1990;211:277–87.
Jonas S, Bechstein WO, Steinmüller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–6.
Taketomi A, Sanefuji K, Soejima Y, et al. Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation. Transplantation. 2009;87:531–7.
Choi GH, Han DH, Kim DH, et al. Outcome after curative resection for a huge (>or=10 cm) hepatocellular carcinoma and prognostic significance of gross tumor classification. Am J Surg. 2009;198:693–701.
Nagano Y, Tanaka K, Togo S, et al. Efficacy of hepatic resection for hepatocellular carcinomas larger than 10 cm. World J Surg. 2005;29:66–71.
Theise ND, Marcelin K, Goldfischer M, Hytiroglou P, Ferrell L, Thung SN. Low proliferative activity in macroregenerative nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis. Liver. 1996;16:134–9.
Yamashita Y, Taketomi A, Itoh S, et al. Longterm favorable results of limited hepatic resections for patients with hepatocellular carcinoma: 20 years of experience. J Am Coll Surg. 2007;205:19–26.
Makuuchi M, Mori T, Gunvén P, Yamazaki S, Hasegawa H. Safety of hemihepatic vascular occlusion during resection of the liver. Surg Gynecol Obstet. 1987;164:155–8.
Lanois B. The intrahepatic Glissonian approach to liver resection. In: Blumgart LH, Fong Y. Surgery of the liver and biliary tract. 3rd ed. Vol. 2. London: WB Saunders, 2000. p. 1698–703.
Shimada M, Hashizume M, Maehara S, et al. Laparoscopic hepatectomy for hepatocellular carcinoma. Surg Endosc. 2001;15:541–4.
Yamashita Y, Shimada M, Hamatsu T, et al. Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial. Arch Surg. 2001;136:328–33.
Yamashita Y, Hamatsu T, Rikimaru T, et al. Bile leakage after hepatic resection. Ann Surg. 2001;233:45–50.
Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer, 5th edn., rev. edn. Tokyo: Kanehara, 2009.
Ueno S, Kubo F, Sakoda M, et al. Efficacy of anatomic resection vs. nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification. J Hepatobiliary Pancreat Surg. 2008;15:493–500.
Takenaka K, Kawahara N, Yamamoto K, et al. Results of 280 liver resections for hepatocellular carcinoma. Arch Surg. 1996;131:71–6.
Shimada M, Takenaka K, Taguchi K, et al. Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma. Ann Surg. 1998;227:80–5.
Takayama T, Makuuchi M, Kojiro M, et al. Early hepatocellular carcinoma: pathology, imaging, and therapy. Ann Surg Oncol. 2008;15:972–8.
Takayama T, Makuuchi M, Hirohashi S, et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology. 1998;28:1241–6.
Livraghi T, Meloni F, Morabito A, Vettori C. Multimodal image-guided tailored therapy of early and intermediate hepatocellular carcinoma: long-term survival in the experience of a single radiologic referral center. Liver Transpl. 2004;10:S98–106.
Todo S, Furukawa H; Japanese Study Group on Organ Transplantation. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg. 2004;240:451–9.
Livraghi T, Meloni F, Di Stasi M, et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology. 2008;47:82–9.
Chen MS, Li JQ, Zheng Y, Guo RP, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006;243:321–8.
Zhou Y, Zhao Y, Li B, et al. Meta-analysis of radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma. BMC Gastroenterol. 2010;10:78.
Makuuchi M, Kokudo N, Arii S, et al. Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res. 2008;38:37–51.
Tsai TJ, Chau GY, Lui WY, et al. Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgery. 2000;127:603–8.
Sumie S, Kuromatsu R, Okuda K, et al. Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol. 2008;15:1375–82.
Jonas S, Bechstein WO, Steinmüller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–6.
Adachi E, Maeda T, Kajiyama K, et al. Factors correlated with portal venous invasion by hepatocellular carcinoma: univariate and multivariate analyses of 232 resected cases without preoperative treatments. Cancer. 1996;77:2022–31.
Eguchi S, Takatsuki M, Hidaka M, et al. Predictor for histological microvascular invasion of hepatocellular carcinoma: a lesson from 229 consecutive cases of curative liver resection. World J Surg. 2010;34:1034–8.
Nakashima Y, Nakashima O, Tanaka M, Okuda K, Nakashima M, Kojiro M. Portal vein invasion and intrahepatic micrometastasis in small hepatocellular carcinoma by gross type. Hepatol Res. 2003;26:142–7.
Shirabe K, Itoh S, Yoshizumi T, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma, with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol. 2007;95:235–40.
Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol. 2010;102:462–8.
Shirabe K, Kajiyama K, Abe T, et al. Predictors of microscopic portal vein invasion by hepatocellular carcinoma: measurement of portal perfusion defect area ratio. J Gastroenterol Hepatol. 2009;24:1431–6.
Miyata R, Tanimoto A, Wakabayashi G, et al. Accuracy of preoperative prediction of microinvasion of portal vein in hepatocellular carcinoma using superparamagnetic iron oxide–enhanced magnetic resonance imaging and computed tomography during hepatic angiography. J Gastroenterol. 2006;41:987–95.
Koike Y, Shiratori Y, Sato S, et al. Des-gamma-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;91:561–9.
Shirabe K, Aishima S, Taketomi A, et al. Prognostic importance of the gross classification of hepatocellular carcinoma in living donor-related liver transplantation. Br J Surg. 2011;98:261–7.
Hui AM, Takayama T, Sano K, et al. Predictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy. J Hepatol. 2000;33:975–9.
Ueno S, Kubo F, Sakoda M, et al. Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification. J Hepatobiliary Pancreat Surg. 2008;15:493–500.
Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg. 2007;245:36–43.
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Yamashita, Yi., Tsuijita, E., Takeishi, K. et al. Predictors for Microinvasion of Small Hepatocellular Carcinoma ≤2 cm. Ann Surg Oncol 19, 2027–2034 (2012). https://doi.org/10.1245/s10434-011-2195-0
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DOI: https://doi.org/10.1245/s10434-011-2195-0