Top

Published in:

01-03-2014 | Hepatobiliary Tumors

Long-Term Outcomes and Prognostic Factors with Reductive Hepatectomy and Sequential Percutaneous Isolated Hepatic Perfusion for Multiple Bilobar Hepatocellular Carcinoma

Authors: Takumi Fukumoto, MD, Masahiro Tominaga, MD, Masahiro Kido, MD, Atsushi Takebe, MD, Motofumi Tanaka, MD, Kaori Kuramitsu, MD, Ippei Matsumoto, MD, Tetsuo Ajiki, MD, Yonson Ku, MD

Published in: Annals of Surgical Oncology | Issue 3/2014

Abstract

Background

Sorafenib is currently recommended as first-line therapy for patients with intermediate or advanced hepatocellular carcinoma (HCC) per Barcelona Clinic Liver Cancer staging. However, the median overall survival (OS) with sorafenib in these patients is 10.7 months with an overall response rate of 2 %. We retrospectively investigated the long-term outcomes and prognostic factors with reductive hepatectomy and sequential percutaneous isolated hepatic perfusion (PIHP) for refractory intermediate or advanced HCC.

Methods

A total of 68 patients who had intermediate or advanced stage HCC without extrahepatic metastases were scheduled for reductive hepatectomy plus PIHP. All patients underwent reductive hepatectomy and PIHP with mitomycin C 20–40 mg/m² and/or doxorubicin 60–120 mg/m² 1–3 months after surgery (mean, 1.51 times/patient).

Results

The objective response rate of PIHP was 70.6 % (complete plus partial response). The median OS of all 68 patients was 25 months, and the 5-year OS rate was 27.6 %. Univariate and multivariate analyses indicated that tumor response to PIHP and normalization of serum des-γ-carboxy prothrombin concentrations after PIHP were independent prognostic factors for OS.

Conclusions

The median OS of the study population treated by reductive hepatectomy and sequential PIHP was 25 months. This treatment strategy can offer a possible curative treatment to patients with refractory intermediate and advanced HCC.

Llovet JM, Bruix J, Gores GJ. Surgical resection versus transplantation for early hepatocellular carcinoma: clues for the best strategy. Hepatology. 2000;31:1019–21.PubMedCrossRef

Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394–403.PubMedCrossRef

Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg. 2002;235:373–82.PubMedCrossRef

Kim WR, Gores GJ, Benson JT, Therneau TM, Melton LJ 3rd. Mortality and hospital utilization for hepatocellular carcinoma in the United States. Gastroenterology. 2005;129:486–93.PubMed

Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–38.PubMedCrossRef

Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.PubMedCrossRef

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef

Shimamura Y, Gunven P, Ishii M, Ono M, Abe K. Debulking surgery and arterial embolization for unresectable liver cancer. Hepatogastroenterology. 1993;40:10–3.PubMed

Yamamoto M, Iizuka H, Matsuda M, Nagahori K, Miura K, Itakura J. The indications for tumor mass reduction surgery and subsequent multidisciplinary treatments in stage IV hepatocellular carcinoma. Surg Today. 1993;23:675–81.PubMedCrossRef

10.

Yamamoto K, Takenaka K, Kawahara N, Shimada M, Shirabe K, Itasaka H, et al. Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index. Arch Surg. 1997;132:120–3.PubMedCrossRef

11.

Wakabayashi H, Ushiyama T, Ishimura K, Izuishi K, Karasawa Y, Masaki T, et al. Significance of reduction surgery in multidisciplinary treatment of advanced hepatocellular carcinoma with multiple intrahepatic lesions. J Surg Oncol. 2003;82:98–103.PubMedCrossRef

12.

Inoue K, Nakamura T, Kinoshita T, Konishi M, Nakagohri T, Oda T, et al. Volume reduction surgery for advanced hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:362–6.PubMedCrossRef

13.

Kobayashi A, Takahashi S, Ishii H, Konishi M, Nakagohri T, Gotohda N, et al. Factors predicting survival in advanced T-staged hepatocellular carcinoma patients treated with reduction hepatectomy followed by transcatheter arterial chemoembolization. Eur J Surg Oncol. 2007;33:1019–24.PubMedCrossRef

14.

Nagano H, Miyamoto A, Wada H, Ota H, Marubashi S, Takeda Y, et al. Interferon-alpha and 5-fluorouracil combination therapy after palliative hepatic resection in patients with advanced hepatocellular carcinoma, portal venous tumor thrombus in the major trunk, and multiple nodules. Cancer. 2007;110:2493–501.PubMedCrossRef

15.

Taniai N, Yoshida H, Mamada Y, Kawano Y, Mizuguchi Y, Akimaru K, et al. Is intraoperative adjuvant therapy effective for satellite lesions in patients undergoing reduction surgery for advanced hepatocellular carcinoma? Hepatogastroenterology. 2006;53:258–61.PubMed

16.

Konishi M, Ryu M, Kinoshita T, Inoue K. Surgical treatment of hepatocellular carcinoma with direct removal of the tumor thrombus in the main portal vein. Hepatogastroenterology. 2001;48:1421–4.PubMed

17.

Gotohda N, Kinoshita T, Konishi M, Nakagohri T, Takahashi S, Furuse J, et al. New indication for reduction surgery in patients with advanced hepatocellular carcinoma with major vascular involvement. World J Surg. 2006;30:431–8.PubMedCrossRef

18.

Bruix J, Llovet JM, Castells A, Montañá X, Brú C, Ayuso MC, et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatology. 1998;27:1578–83.PubMedCrossRef

19.

Ku Y, Iwasaki T, Tominaga M, Fukumoto T, Takahashi T, Kido M, et al. Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma. Ann Surg. 2004;239:53–60.PubMedCrossRef

20.

Ku Y, Saitoh M, Iwasaki T, Tominaga M, Maekawa Y, Shiki H, et al. Intraarterial infusion of high-dose adriamycin for unresectable hepatocellular carcinoma using direct hemoperfusion under hepatic venous isolation. Eur J Surg Oncol. 1993;19:387–92.PubMed

21.

Ku Y, Fukumoto T, Iwasaki T, Tominaga M, Samizo M, Nishida T, et al. Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma. Surgery. 1995;117:510–9.PubMedCrossRef

22.

Ku Y, Fukumoto T, Tominaga M, Iwasaki T, Maeda I, Kusunoki N, et al. Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors. Am J Surg. 1997;173:103–9.PubMedCrossRef

23.

Ku Y, Iwasaki T, Fukumoto T, Tominaga M, Muramatsu S, Kusunoki N, et al. Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion. Ann Surg. 1998;227:519–26.PubMedCrossRef

24.

Group d’Etude et de Traitement du Carcinoma Hepatocellulaire. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Engl J Med. 1995;332:1256–61.CrossRef

25.

Liver Cancer Study Group of Japan. General rules for the clinical and pathological study of primary liver cancer. 3rd English ed. Tokyo: Kanehara; 2010.

26.

Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. International Union against Cancer. 7th ed. Oxford: Wiley; 2009.

27.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRef

28.

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. 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. 2009;10:25–34.PubMedCrossRef

29.

Villa E, Moles A, Ferretti I, Buttafoco P, Grottola A, Del Buono M, et al. Natural history of inoperable hepatocellular carcinoma: estrogen receptors’ status in the tumor is the strongest prognostic factor for survival. Hepatology. 2000;32:233–8.PubMedCrossRef

30.

Friedman MA. Primary hepatocellular cancer—present results and future prospects. Int J Radiat Oncol Biol Phys. 1983;9:1841–50.PubMedCrossRef

31.

Lai CL, Wu PC, Chan GC, Lok AS, Lin HJ. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer. 1988;62:479–83.PubMedCrossRef

32.

Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999;29:62–7.PubMedCrossRef

33.

Fujikawa T, Shiraha H, Ueda N, Takaoka N, Nakanishi Y, Matsuo N, et al. Des-gamma-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migration. J Biol Chem. 2007;282:8741–8.PubMedCrossRef

34.

Ikai I, Hatano E, Hasegawa S, Fujii H, Taura K, Uyama N, et al. Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein. J Am Coll Surg. 2006;202:431–8.PubMedCrossRef

35.

Pawlik TM, Poon RT, Abdalla EK, Ikai I, Nagorney DM, Belghiti J, et al. Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: results of a multicenter study. Surgery. 2005;137:403–10.PubMedCrossRef

36.

Zhou J, Tang ZY, Wu ZQ, Zhou XD, Ma ZC, Tan CJ, et al. Factors influencing survival in hepatocellular carcinoma patients with macroscopic portal vein tumor thrombosis after surgery, with special reference to time dependency: a single-center experience of 381 cases. Hepatogastroenterology. 2006;53:275–80.PubMed

37.

Minagawa M, Makuuchi M, Takayama T, Ohtomo K. Selection criteria for hepatectomy in patients with hepatocellular carcinoma and portal vein tumor thrombus. Ann Surg. 2001;233:379–84. PubMedCrossRef

Title: Long-Term Outcomes and Prognostic Factors with Reductive Hepatectomy and Sequential Percutaneous Isolated Hepatic Perfusion for Multiple Bilobar Hepatocellular Carcinoma
Authors: Takumi Fukumoto, MD
Masahiro Tominaga, MD
Masahiro Kido, MD
Atsushi Takebe, MD
Motofumi Tanaka, MD
Kaori Kuramitsu, MD
Ippei Matsumoto, MD
Tetsuo Ajiki, MD
Yonson Ku, MD
Publication date: 01-03-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue 3/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-013-3305-y

At a glance: The STEP trials

Springer Medicine

Long-Term Outcomes and Prognostic Factors with Reductive Hepatectomy and Sequential Percutaneous Isolated Hepatic Perfusion for Multiple Bilobar Hepatocellular Carcinoma

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2014

Quilting Prevents Seroma Formation Following Breast Cancer Surgery: Closing the Dead Space by Quilting Prevents Seroma Following Axillary Lymph Node Dissection and Mastectomy

Association of a Genetic Variant of CYP19A1 with Multicentric Development of Lung Adenocarcinomas

The Addition of Radiation to Chemotherapy does not Improve Outcome When Compared to Chemotherapy in the Treatment of Resected Pancreas Cancer: The Results of a Single-Institution Experience

Intensity of Follow-Up After Breast Cancer Surgery: Low Versus High?

EGFR, BRAF and KRAS Status in Patients Undergoing Pulmonary Metastasectomy from Primary Colorectal Carcinoma: A Prospective Follow-Up Study

Anatomic Extent of Metastatic Lymph Nodes: Still Important for Gastric Cancer Prognosis