Abstract
Purpose
The purpose of this study was to clarify the clinicopathological features of extrahepatic hepatocellular carcinoma (HCC) recurrence after hepatectomy in order to schedule optimal treatment strategies for better long-term outcomes.
Methods
A cohort of 206 patients who had undergone curative hepatectomy for HCC was analysed; 133 patients had developed relapse. Among them, 101 patients had intrahepatic recurrence only (IHR), and 32 patients had extrahepatic recurrence (EHR). Clinicopathological and survival data were compared between the two groups.
Results
The overall survival rate after hepatectomy was better in the IHR than in the EHR group (p < 0.0001). The recurrence-free interval after hepatectomy was significantly shorter in the EHR than in the IHR group (258 vs. 487 days, p < 0.0043). Patients in the EHR group were more likely to have a high PIVKA II, a large tumour, and microscopic portal vein invasion when compared with patients in the IHR group. Microscopic portal vein invasion was the most important independent risk factor for EHR after hepatectomy (p = 0.0295). Patients with more than two risk factors for EHR showed poor prognosis in comparison with patients without any risk factors (p < 0.001). In the EHR group, patients who underwent repeated resection had significantly better survival than patients receiving only the best supportive care (539 vs. 133 days, p = 0.0098). Furthermore, among EHR patients with concomitant IHR, patients with controllable IHR had significantly better survival than those with uncontrollable IHR (524 vs. 147 days, p = 0.0131).
Conclusions
EHR of HCC was associated with early recurrence, and risk factors for the occurrence of EHR included the presence of high PIVKA II, large tumours, and microscopic portal vein invasion. Resection of recurrent tumour and local control of concomitant IHR may improve the prognosis of EHR patients.
Similar content being viewed by others
References
Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y et al (1999) No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach. Arch Surg 134(9):984–992
Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C et al (1999) Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg 229(3):322–330
Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM et al (2001) Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 234(1):63–70
Ercolani G, Grazi GL, Ravaioli M, Del Gaudio M, Gardini A, Cescon M et al (2003) Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg 237(4):536–543
Chan KM, Yu MC, Wu TJ, Lee CF, Chen TC, Lee WC et al (2009) Efficacy of surgical resection in management of isolated extrahepatic metastases of hepatocellular carcinoma. World J Gastroenterol 15(43):5481–5488
Taketomi A, Toshima T, Kitagawa D, Motomura T, Takeishi K, Mano Y et al (2010) Predictors of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol 17(10):2740–2746
Shimada M, Takenaka K, Gion T, Fujiwara Y, Kajiyama K, Maeda T et al (1996) Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan. Gastroenterology 111(3):720–726
Choi D, Lim HK, Rhim H, Kim YS, Yoo BC, Paik SW et al (2007) Percutaneous radiofrequency ablation for recurrent hepatocellular carcinoma after hepatectomy: long-term results and prognostic factors. Ann Surg Oncol 14(8):2319–2329
Taketomi A, Sanefuji K, Soejima Y, Yoshizumi T, Uhciyama H, Ikegami T et al (2009) Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation. Transplantation 87(4):531–537
Yang Y, Nagano H, Ota H, Morimoto O, Nakamura M, Wada H et al (2007) Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery 141(2):196–202
Tanaka K, Shimada H, Matsuo K, Takeda K, Nagano Y, Togo S (2008) Clinical features of hepatocellular carcinoma developing extrahepatic recurrences after curative resection. World J Surg 32(8):1738–1747
Ishii H, Furuse J, Kinoshita T, Konishi M, Nakagohri T, Takahashi S et al (2004) Extrahepatic spread from hepatocellular carcinoma: who are candidates for aggressive anti-cancer treatment? Jpn J Clin Oncol 34(12):733–739
Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K et al (2007) Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol 13(3):414–420
Hirokawa F, Hayashi M, Miyamoto Y, Iwamoto M, Tsunematsu I, Asakuma M et al (2011) A novel method using the VIO soft-coagulation system for liver resection. Surgery 149(3):438–444
Kudo M, Okanoue T (2007) Management of hepatocellular carcinoma in Japan: consensus-based clinical practice manual proposed by the Japan Society of Hepatology. Oncology 72(Suppl 1):2–15
Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F (1991) Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg 214(2):114–117
Takenaka K, Kawahara N, Yamamoto K, Kajiyama K, Maeda T, Itasaka H et al (1996) Results of 280 liver resections for hepatocellular carcinoma. Arch Surg 131(1):71–76
Balsells J, Charco R, Lazaro JL, Murio E, Vargas V, Allende E et al (1996) Resection of hepatocellular carcinoma in patients with cirrhosis. Br J Surg 83(6):758–761
Arii S, Sata M, Sakamoto M, Shimada M, Kumada T, Shiina S et al (2010) Management of hepatocellular carcinoma: report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009). Hepatol Res 40(7):667–685
Si MS, Amersi F, Golish SR, Ortiz JA, Zaky J, Finklestein D et al (2003) Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg 69(10):879–885
Ochiai T, Ikoma H, Okamoto K, Kokuba Y, Sonoyama T, Otsuji E (2012) Clinicopathologic features and risk factors for extrahepatic recurrences of hepatocellular carcinoma after curative resection. World J Surg 36(1):136–143
Utsunomiya T, Shimada M, Shirabe K, Kajiyama K, Gion T, Takenaka K et al (2001) Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma. Hepatogastroenterology 48(40):1088–1093
Sasaki A, Kai S, Endo Y, Iwaki K, Uchida H, Shibata K et al (2007) Hepatitis B virus infection predicts extrahepatic metastasis after hepatic resection in patients with large hepatocellular carcinoma. Ann Surg Oncol 14(11):3181–3187
Ogawa M, Yamamoto T, Kubo S, Uenishi T, Tanaka H, Shuto T et al (2004) Clinicopathologic analysis of risk factors for distant metastasis of hepatocellular carcinoma. Hepatol Res 29(4):228–234
Liu Y, Wu MC, Qian GX, Zhang BH (2002) Detection of circulating hepatocellular carcinoma cells in peripheral venous blood by reverse transcription-polymerase chain reaction. Hepatobiliary Pancreat Dis Int 1(1):72–76
Marubashi S, Nagano H, Wada H, Kobayashi S, Eguchi H, Takeda Y et al (2011) Clinical significance of alpha-fetoprotein mRNA in peripheral blood in liver resection for hepatocellular carcinoma. Ann Surg Oncol 18(8):2200–2209
Taniai N, Egami K, Wada M, Tajiri T, Onda M (1999) Adrenal metastasis from hepatocellular carcinoma (HCC): report of 3 cases. Hepatogastroenterology 46(28):2523–2528
Yoon YS, Kim HK, Kim J, Choi YS, Shim YM, Paik SW et al (2010) Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol 17(10):2795–2801
Chua TC, Morris DL (2012) Exploring the role of resection of extrahepatic metastases from hepatocellular carcinoma. Surg Oncol 21(2):95–101
Sano T, Izuishi K, Takebayashi R, Akamoto S, Kakinoki K, Okano K et al (2011) Surgical approach for extrahepatic metastasis of HCC in the abdominal cavity. Hepatogastroenterology 58(112):2067–2070
Yoon KT, Kim JK, Kimdo Y, Ahn SH, Lee JD, Yun M et al (2007) Role of 18 F-fluorodeoxyglucose positron emission tomography in detecting extrahepatic metastasis in pretreatment staging of hepatocellular carcinoma. Oncology 72(Suppl 1):104–110
Sun L, Guan YS, Pan WM, Chen GB, Luo ZM, Wu H (2007) Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management. World J Gastroenterol 13(40):5413–5415
Lin CY, Chen JH, Liang JA, Lin CC, Jeng LB, Kao CH (2012) 18 F-FDG PET or PET/CT for detecting extrahepatic metastases or recurrent hepatocellular carcinoma: a systematic review and meta-analysis. Eur J Radiol 81(9):2417–2422
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(1):25–34
Richly H, Schultheis B, Adamietz IA, Kupsch P, Grubert M, Hilger RA et al (2009) Combination of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma: results from a phase I extension trial. Eur J Cancer 45(4):579–587
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hirokawa, F., Hayashi, M., Miyamoto, Y. et al. Surgical treatment of extrahepatic recurrence of hepatocellular carcinoma. Langenbecks Arch Surg 399, 1057–1064 (2014). https://doi.org/10.1007/s00423-014-1230-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-014-1230-6