Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 8/2012

01-08-2012 | Original Article

Role of Operative Therapy in Non-cirrhotic Patients with Metastatic Hepatocellular Carcinoma

Authors: Victor Zaydfudim, Rory L. Smoot, Clancy J. Clark, Michael L. Kendrick, Florencia G. Que, Michael B. Farnell, David M. Nagorney

Published in: Journal of Gastrointestinal Surgery | Issue 8/2012

Login to get access

Abstract

Introduction

We investigated the role of operative therapy in non-cirrhotic patients who developed metastatic hepatocellular carcinoma (HCC).

Methods

This retrospective cohort study included consecutive non-cirrhotic patients with metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients were stratified by operative therapy (resection, ablation, transcatheter therapy). Kaplan–Meier analyses with log-rank comparisons tested effects of operative therapy on overall survival (OS) and progression-free survival (PFS).

Results

Of 195 non-cirrhotic patients treated for HCC during the study period, 98 [median age 65, interquartile range (IQR) 53–71; 55 % male] subsequently developed metastatic HCC (55 intrahepatic only). Median time to development of metastases after the index operation was 10 months (IQR 5–20 months); median number of metastases was 3 (IQR 2–7). Half of these patients (n = 50) underwent operative treatment of metastases; 20 (40 %) underwent metastasectomy, 18 (36 %) ablation, and 12 (24 %) transcatheter therapy. Operative therapy was associated with improved OS (p < 0.001). Resection or ablation was associated with improved PFS and OS compared to transcatheter therapy (all p ≤ 0.006). Nine patients (seven resection, two ablation) are disease free at a median of 50 months (IQR 24–80 months) posttreatment.

Conclusions

Resection and ablation are associated with an improved PFS and long-term OS and should be considered in select patients with metastatic HCC.
Literature
1.
go back to reference Benson AB, 3rd, Abrams TA, Ben-Josef E, et al. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 2009;7:350–91.PubMed Benson AB, 3rd, Abrams TA, Ben-Josef E, et al. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 2009;7:350–91.PubMed
2.
go back to reference Jung SM, Jang JW, You CR, et al. Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases. J Gastroenterol Hepatol 2012; 27:684–89.PubMedCrossRef Jung SM, Jang JW, You CR, et al. Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases. J Gastroenterol Hepatol 2012; 27:684–89.PubMedCrossRef
4.
go back to reference Leong TY, Leong AS. Epidemiology and carcinogenesis of hepatocellular carcinoma. HPB (Oxford) 2005;7:5–15.CrossRef Leong TY, Leong AS. Epidemiology and carcinogenesis of hepatocellular carcinoma. HPB (Oxford) 2005;7:5–15.CrossRef
5.
go back to reference Sherman M. Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin Liver Dis 2010;30:3–16.PubMedCrossRef Sherman M. Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin Liver Dis 2010;30:3–16.PubMedCrossRef
6.
go back to reference Jarnagin W, Chapman WC, Curley S, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB (Oxford) 2010;12:302–10. Jarnagin W, Chapman WC, Curley S, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB (Oxford) 2010;12:302–10.
7.
go back to reference Smoot RL, Nagorney DM, Chandan VS, et al. Resection of hepatocellular carcinoma in patients without cirrhosis. Br J Surg 2011;98:697–703.PubMedCrossRef Smoot RL, Nagorney DM, Chandan VS, et al. Resection of hepatocellular carcinoma in patients without cirrhosis. Br J Surg 2011;98:697–703.PubMedCrossRef
9.
go back to reference Cha C, Fong Y, Jarnagin WR, Blumgart LH, DeMatteo RP. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg 2003;197:753–8.PubMedCrossRef Cha C, Fong Y, Jarnagin WR, Blumgart LH, DeMatteo RP. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg 2003;197:753–8.PubMedCrossRef
10.
go back to reference Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37:429–42.PubMedCrossRef Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37:429–42.PubMedCrossRef
11.
go back to reference Nowak AK, Chow PK, Findlay M. Systemic therapy for advanced hepatocellular carcinoma: a review. Eur J Cancer 2004;40:1474–84.PubMedCrossRef Nowak AK, Chow PK, Findlay M. Systemic therapy for advanced hepatocellular carcinoma: a review. Eur J Cancer 2004;40:1474–84.PubMedCrossRef
12.
go back to reference Samuel M, Chow PK, Chan Shih-Yen E, Machin D, Soo KC. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev 2009:CD001199. Samuel M, Chow PK, Chan Shih-Yen E, Machin D, Soo KC. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev 2009:CD001199.
13.
go back to reference Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–90.PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–90.PubMedCrossRef
14.
go back to reference Hirokawa F, Hayashi M, Miyamoto Y, et al. Appropriate treatment strategy for intrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. J Gastrointest Surg 2011;15:1182–7.PubMedCrossRef Hirokawa F, Hayashi M, Miyamoto Y, et al. Appropriate treatment strategy for intrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. J Gastrointest Surg 2011;15:1182–7.PubMedCrossRef
15.
go back to reference Kwon JB, Park K, Kim YD, et al. Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma: analysis of prognostic factors. World J Gastroenterol 2008;14:5717–22.PubMedCrossRef Kwon JB, Park K, Kim YD, et al. Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma: analysis of prognostic factors. World J Gastroenterol 2008;14:5717–22.PubMedCrossRef
16.
go back to reference Yoon YS, Kim HK, Kim J, et al. Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol 2010;17:2795–801.PubMedCrossRef Yoon YS, Kim HK, Kim J, et al. Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol 2010;17:2795–801.PubMedCrossRef
17.
go back to reference Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. Seventh ed. New York: Springer; 2010. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. Seventh ed. New York: Springer; 2010.
18.
go back to reference Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.
19.
go back to reference Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res 1980;47:1–9.PubMedCrossRef Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res 1980;47:1–9.PubMedCrossRef
20.
go back to reference Zhu AX. Systemic treatment of hepatocellular carcinoma: dawn of a new era? Ann Surg Oncol 2010;17:1247–56.PubMedCrossRef Zhu AX. Systemic treatment of hepatocellular carcinoma: dawn of a new era? Ann Surg Oncol 2010;17:1247–56.PubMedCrossRef
21.
go back to reference Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008;48:1312–27.PubMedCrossRef Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008;48:1312–27.PubMedCrossRef
22.
go back to reference Villanueva A, Minguez B, Forner A, Reig M, Llovet JM. Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis, and therapy. Annu Rev Med 2010;61:317–28.PubMedCrossRef Villanueva A, Minguez B, Forner A, Reig M, Llovet JM. Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis, and therapy. Annu Rev Med 2010;61:317–28.PubMedCrossRef
23.
go back to reference Sieghart W, Pinter M, Reisegger M, et al. Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study. Eur Radiol 2012 (published ahead of print date; doi:10/1007/s00330-011-2368-z). Sieghart W, Pinter M, Reisegger M, et al. Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study. Eur Radiol 2012 (published ahead of print date; doi:10/​1007/​s00330-011-2368-z).
24.
go back to reference Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 1999;229:216–22.PubMedCrossRef Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 1999;229:216–22.PubMedCrossRef
25.
go back to reference Farges O, Regimbeau JM, Belghiti J. Aggressive management of recurrence following surgical resection of hepatocellular carcinoma. Hepatogastroenterology 1998;45 Suppl 3:1275–80.PubMed Farges O, Regimbeau JM, Belghiti J. Aggressive management of recurrence following surgical resection of hepatocellular carcinoma. Hepatogastroenterology 1998;45 Suppl 3:1275–80.PubMed
26.
go back to reference Poon RT, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000;232:10–24.CrossRef Poon RT, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000;232:10–24.CrossRef
27.
go back to reference Ho CM, Lee PH, Shau WY, Ho MC, Wu YM, Hu RH. Survival in patients with recurrent hepatocellular carcinoma after primary hepatectomy: Comparative effectiveness of treatment modalities. Surgery 2012;151:700–09.PubMedCrossRef Ho CM, Lee PH, Shau WY, Ho MC, Wu YM, Hu RH. Survival in patients with recurrent hepatocellular carcinoma after primary hepatectomy: Comparative effectiveness of treatment modalities. Surgery 2012;151:700–09.PubMedCrossRef
28.
go back to reference Sakamoto Y, Kubota K, Mori M, et al. Surgical management for adrenal gland metastasis of hepatocellular carcinoma. Hepatogastroenterology 1999;46:1036–41.PubMed Sakamoto Y, Kubota K, Mori M, et al. Surgical management for adrenal gland metastasis of hepatocellular carcinoma. Hepatogastroenterology 1999;46:1036–41.PubMed
29.
go back to reference Nakayama H, Takayama T, Makuuchi M, et al. Resection of peritoneal metastases from hepatocellular carcinoma. Hepatogastroenterology 1999;46:1049–52.PubMed Nakayama H, Takayama T, Makuuchi M, et al. Resection of peritoneal metastases from hepatocellular carcinoma. Hepatogastroenterology 1999;46:1049–52.PubMed
30.
go back to reference Gordon-Weeks AN, Snaith A, Petrinic T, Friend PJ, Burls A, Silva MA. Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria. Br J Surg 2011;98:1201–8.PubMedCrossRef Gordon-Weeks AN, Snaith A, Petrinic T, Friend PJ, Burls A, Silva MA. Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria. Br J Surg 2011;98:1201–8.PubMedCrossRef
31.
go back to reference Davis E, Wiesner R, Valdecasas J, Kita Y, Rossi M, Schwartz M. Treatment of recurrent hepatocellular carcinoma after liver transplantation. Liver Transpl 2011;17 Suppl 2:S162–6.PubMedCrossRef Davis E, Wiesner R, Valdecasas J, Kita Y, Rossi M, Schwartz M. Treatment of recurrent hepatocellular carcinoma after liver transplantation. Liver Transpl 2011;17 Suppl 2:S162–6.PubMedCrossRef
Metadata
Title
Role of Operative Therapy in Non-cirrhotic Patients with Metastatic Hepatocellular Carcinoma
Authors
Victor Zaydfudim
Rory L. Smoot
Clancy J. Clark
Michael L. Kendrick
Florencia G. Que
Michael B. Farnell
David M. Nagorney
Publication date
01-08-2012
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 8/2012
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-012-1918-2

Other articles of this Issue 8/2012

Journal of Gastrointestinal Surgery 8/2012 Go to the issue