The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone.
From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900).
The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients.
Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.
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Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35–50.
Lau WY, Lai EC, Leung TW, Yu SC. Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival. Ann Surg. 2008;247:43–8.
Lai EC, Lo CM, Fan ST, Liu CL, Wong J. Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial. Arch Surg. 1998;133:183–8.
Cheng HY, Wang X, Chen D, Xu AM, Jia YC. The value and limitation of transcatheter arterial chemoembolization in preventing recurrence of resected hepatocellular carcinoma. World J Gastroenterol. 2005;11:3644–6.
Ueno S, Tanabe G, Yoshida A, Yoshidome S, Takao S, Aikou, T. Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis. Cancer. 1999;86:248–54.
Boucher E, Corbinais S, Rolland Y, et al. Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma. Hepatology. 2003;38:1237–41.
Takayama T, Sekine T, Makuuchi M, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000;356:802–7.
Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Shuto T, Kinoshita, H. Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy. Br J Surg. 2002;89:418–22.
Sun HC, Tang ZY, Wang L, et al. 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. 2006;132:458–65.
Peng BG, Liang LJ, He Q, et al. Tumor vaccine against recurrence of hepatocellular carcinoma. World J Gastroenterol. 2005;11:700–4.
Muto Y, Moriwaki H, Ninomiya M, et al. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med. 1996;334:1561–1567.
Cammà C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224:47–54.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–42.
Ramsey DE, Geschwind JF. Chemoembolization of hepatocellular carcinoma: what to tell the skeptics: review and meta-analysis. Tech Vasc Interv Radiol. 2002;5:122–6.
Shin SW. The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol. 2009;10:425–34.
Timm S, Sotiropoulos GC, Draier M, Knüpffer J, Steger U, Lang, H. Selective transarterial chemoembolization of advanced hepatocellular carcinomas: a reasonable palliative option. Transplant Proc. 2008;40:3179–81.
Liu Y, Yang R. Preoperative combined with postoperative chemoembolization can improve survival in patients with hepatocellular carcinoma: a single-center study. J Vasc Interv Radiol. 2009;20:472–83.
Ren ZG, Lin ZY, Xia JL, et al. Postoperative adjuvant arterial chemoembolization improves survival of hepatocellular carcinoma patients with risk factors for residual tumor: a retrospective control study. World J Gastroenterol. 2004;10:2791–4.
Shimoda M, Bando T, Nagata T, Shirosaki I, Sakamoto T, Tsukada, K. Prophylactic chemolipiodolization for postoperative hepatoma patients. Hepatogastroenterology. 2001;48:493–7.
Shuqun C, Mengchao W, Han C, et al. Combination transcatheter hepatic arterial chemoembolization with thymosin alpha1 on recurrence prevention of hepatocellular carcinoma. Hepatogastroenterology. 2004;51:1445–7.
Izumi R, Shimizu K, Iyobe T, et al. Postoperative adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology. 1994;20:295–301.
Li JQ, Zhang YQ, Zhang WZ, Yuan YF, Li GH. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol. 1995;121:364–6.
Li Q, Wang J, Sun Y, et al. Postoperative transhepatic arterial chemoembolization and portal vein chemotherapy for patients with hepatocellular carcinoma: a randomized study with 131 cases. Dig Surg. 2006;23:235–40.
Peng BG, He Q, Li JP, Zhou F. Adjuvant transcatheter arterial chemoembolization improves efficacy of hepatectomy for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Surg. 2009;198:313–8.
Zhong C, Guo RP, Li JQ, et al. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol. 2009;135:1437–45.
Lau WY, Lai EC, Lau SH. The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma: a systematic review. Hepatobil Pancreat Dis Int. 2009;8:124–133.
Marelli L, Stigliano R, Triantos C, et al. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev. 2006;32:594–606.
Mathurin P, Raynard B, Dharancy S, et al. Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma. Aliment Pharmacol Ther. 2003;17:1247–61.
Samuel M, Chow PK, Chan Shih-Yen E, et al. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev. 2009;2009:CD001199. https://doi.org/10.1002/14651858.CD001199.pub2.
Schwartz JD, Schwartz M, Mandeli J, Sung M. Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials. Lancet Oncol. 2002;3:593–603.
Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early- and late-phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.
Ishikawa T, Higuchi K, Kubota T, et al. Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma. Cancer. 2011;117:4018–25.
Fan J, Zhou J, Wu ZQ, et al. Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol. 2005;11:1215–9.
Asahara T, Itamoto T, Katayama K, et al. Adjuvant hepatic arterial infusion chemotherapy after radical hepatectomy for hepatocellular carcinoma: results of long-term follow-up. Hepatogastroenterology. 1999;46:1042–8.
Feng AL, Zhu JK, Yang Y, et al. Repeated postoperative adjuvant TACE after curative hepatectomy improves outcomes of patients with HCC. Minim Invasive Ther Allied Technol. 2019. https://doi.org/10.1080/13645706.2019.1707689.
Chen H, Hu N, Chang P. et al. Modified Glasgow prognostic score might be a prognostic factor for hepatocellular carcinoma: a meta-analysis. Panminerva Med. 2017;59:302–7.
Fujiwara Y, Shiba H, Furukawa K, et al. Glasgow prognostic score is related to blood transfusion requirements and postoperative complications in hepatic resection for hepatocellular carcinoma. Anticancer Res. 2010;30:5129–36.
Glen P, Jamieson NB, McMillan DC, et al. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.
Kobayashi T, Teruya M, Kishiki T, et al. Inflammation-based prognostic score and number of lymph node metastases are independent prognostic factors in esophageal squamous cell carcinoma. Dig Surg. 2010;27:232–7.
Neofytou K, Smyth EC, Giakoustidis A, et al. The preoperative lymphocyte-to-monocyte ratio is prognostic of clinical outcomes for patients with liver-only colorectal metastases in the neoadjuvant setting. Ann Surg Oncol. 2015;22:4353–62.
Donadon M, Cimino M, Procopio F, et al. Potential role of cholinesterases to predict short-term outcome after hepatic resection for hepatocellular carcinoma. Updates Surg. 2013;65:11–8.
Donadon M, Costa G, Cimino M, et al. Safe hepatectomy selection criteria for hepatocellular carcinoma patients: a validation of 336 consecutive hepatectomies. The BILCHE score. World J Surg. 2015;39:237–43.
Takaki S, Fukuhara T, Mori N, Tsuji K. High cholinesterase predicts tolerance to sorafenib treatment and improved prognosis in patients with transarterial chemoembolization refractory intermediate stage hepatocellular carcinoma. Mol Clin Oncol. 2020;12:60–8.
Barquero-Quirós M, Dominguez-Renedo O, Alonso-Lomillo MA, Arcos-Martinez MJ. Acetylcholinesterase inhibition-based biosensor for aluminum(III) chronoamperometric determination in aqueous media. Sensors Basel. 2014;14:8203–16.
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Hirokawa, F., Komeda, K., Taniguchi, K. et al. Is Postoperative Adjuvant Transcatheter Arterial Infusion Therapy Effective for Patients with Hepatocellular Carcinoma who Underwent Hepatectomy? A Prospective Randomized Controlled Trial. Ann Surg Oncol 27, 4143–4152 (2020). https://doi.org/10.1245/s10434-020-08699-w