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Published in: Updates in Surgery 1/2019

01-03-2019 | Esophageal Varices | Original Article

Dissecting the multinodular hepatocellular carcinoma subset: is there a survival benefit after hepatectomy?

Authors: Matteo Donadon, Andrea Fontana, Fabio Procopio, Daniele Del Fabbro, Matteo Cimino, Luca Viganò, Angela Palmisano, Guido Torzilli

Published in: Updates in Surgery | Issue 1/2019

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Abstract

Whether hepatic resection for multinodular hepatocellular carcinoma (HCC) is indicated remains to be demonstrated. We investigated the prognostic factors in a large series of patients treated with hepatic resection at a reference cancer center. All consecutive patients resected for multinodular HCC from January 2004 to April 2015 were reviewed. The study endpoints were the survival analysis and the definition of resection criteria. Among 380 patients resected for HCC, 116 (31%) were affected by multinodular HCC without macrovascular invasion. The median tumor number was 2 (range 2–30), while the median tumor size was 3.5 cm (range 1.1–28). The 90-day mortality was 2.6%. Morbidity was 31%. After a median follow-up of 31 months (range 3.1–149.7), the 1-, 3-, and 5-year overall survival rates were 85, 52, and 35%, respectively. At the multivariate analysis, tumor number more than 4 (HR = 2.15; 95% CI 1.8–4.18; P = 0.001), tumor size more than 6 cm (HR = 2.78; 95% CI 2.08–4.91; P = 0.001), esophageal varices (HR = 3.01; 95% CI 1.98–5.61; P = 0.002), and major hepatectomy (HR = 2.91; 95% CI 1.97–4.54; P = 0.001) were independently significant for survival. Median survival shifted from 20 to 52 months based on these factors. Hepatic resection for multinodular HCC may result in survival benefit for patients up to four tumors, none more than 6 cm, without varices, and eventually treated by conservative surgery.
Literature
1.
go back to reference Venook AP, Papandreou C, Furuse J et al (2010) The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 15(Suppl 4):5–13CrossRefPubMed Venook AP, Papandreou C, Furuse J et al (2010) The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 15(Suppl 4):5–13CrossRefPubMed
2.
go back to reference Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43CrossRefPubMed Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43CrossRefPubMed
3.
go back to reference European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRef European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRef
4.
go back to reference Torzilli G, Belghiti J, Kokudo N et al (2013) A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations?: an observational study of the HCC East-West study group. Ann Surg 257:929–937CrossRefPubMed Torzilli G, Belghiti J, Kokudo N et al (2013) A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations?: an observational study of the HCC East-West study group. Ann Surg 257:929–937CrossRefPubMed
5.
go back to reference Roayaie S, Jibara G, Tabrizian P et al (2015) The role of hepatic resection in the treatment of hepatocellular cancer. Hepatology 62:440–451CrossRefPubMed Roayaie S, Jibara G, Tabrizian P et al (2015) The role of hepatic resection in the treatment of hepatocellular cancer. Hepatology 62:440–451CrossRefPubMed
6.
go back to reference Ciria R, Lopez-Cillero P, Gallardo AB et al (2015) Optimizing the management of patients with BCLC stage-B hepatocellular carcinoma: modern surgical resection as a feasible alternative to transarterial chemoemolization. Eur J Surg Oncol 41:1153–1161CrossRefPubMed Ciria R, Lopez-Cillero P, Gallardo AB et al (2015) Optimizing the management of patients with BCLC stage-B hepatocellular carcinoma: modern surgical resection as a feasible alternative to transarterial chemoemolization. Eur J Surg Oncol 41:1153–1161CrossRefPubMed
7.
go back to reference Torzilli G, Donadon M, Belghiti J et al (2016) Predicting individual survival after hepatectomy for hepatocellular carcinoma: a novel nomogram from the “HCC East & West Study Group”. J Gastrointest Surg 20:1154–1162CrossRefPubMed Torzilli G, Donadon M, Belghiti J et al (2016) Predicting individual survival after hepatectomy for hepatocellular carcinoma: a novel nomogram from the “HCC East & West Study Group”. J Gastrointest Surg 20:1154–1162CrossRefPubMed
8.
go back to reference Belghiti J, Clavien P, Gadzijev E (2000) The Brisbane 2000 terminology of liver anatomy and resections. HPB (Oxford) 2:333–339CrossRef Belghiti J, Clavien P, Gadzijev E (2000) The Brisbane 2000 terminology of liver anatomy and resections. HPB (Oxford) 2:333–339CrossRef
9.
go back to reference Dindo D, Demartines N, Clavien P-A (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213CrossRefPubMedPubMedCentral Dindo D, Demartines N, Clavien P-A (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213CrossRefPubMedPubMedCentral
10.
go back to reference Donadon M, Costa G, Cimino M et al (2014) Safe hepatectomy selection criteria for hepatocellular carcinoma patients: a validation of 336 consecutive hepatectomies. The BILCHE score. World J Surg 39:237–243CrossRef Donadon M, Costa G, Cimino M et al (2014) Safe hepatectomy selection criteria for hepatocellular carcinoma patients: a validation of 336 consecutive hepatectomies. The BILCHE score. World J Surg 39:237–243CrossRef
11.
go back to reference Pugh RNH, Murray-Lyon IM, Dawson JL et al (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649CrossRefPubMed Pugh RNH, Murray-Lyon IM, Dawson JL et al (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649CrossRefPubMed
12.
go back to reference Torzilli G, Donadon M, Marconi M et al (2008) Hepatectomy for stage b and stage c hepatocellular carcinoma in the barcelona clinic liver cancer classification: results of a prospective analysis. Arch Surg 143:1082–1090CrossRefPubMed Torzilli G, Donadon M, Marconi M et al (2008) Hepatectomy for stage b and stage c hepatocellular carcinoma in the barcelona clinic liver cancer classification: results of a prospective analysis. Arch Surg 143:1082–1090CrossRefPubMed
13.
go back to reference Kinoshita H, Sakai K, Hirohashi K et al (1986) Preoperative portal vein embolization for hepatocellular carcinoma. World J Surg 10:803–808CrossRefPubMed Kinoshita H, Sakai K, Hirohashi K et al (1986) Preoperative portal vein embolization for hepatocellular carcinoma. World J Surg 10:803–808CrossRefPubMed
14.
go back to reference Torzilli G, Montorsi M, Donadon M et al (2005) “Radical but conservative” is the main goal for ultrasonography-guided liver resection: prospective validation of this approach. J Am Coll Surg 201:517–528CrossRefPubMed Torzilli G, Montorsi M, Donadon M et al (2005) “Radical but conservative” is the main goal for ultrasonography-guided liver resection: prospective validation of this approach. J Am Coll Surg 201:517–528CrossRefPubMed
15.
go back to reference Torzilli G, Procopio F, Cimino M et al (2010) Anatomical segmental and subsegmental resection of the liver for hepatocellular carcinoma: a new approach by means of ultrasound-guided vessel compression. Ann Surg 251:229–235CrossRefPubMed Torzilli G, Procopio F, Cimino M et al (2010) Anatomical segmental and subsegmental resection of the liver for hepatocellular carcinoma: a new approach by means of ultrasound-guided vessel compression. Ann Surg 251:229–235CrossRefPubMed
16.
go back to reference Torzilli G (2014) Ultrasound-guided liver surgery: an atlas. Springer, BerlinCrossRef Torzilli G (2014) Ultrasound-guided liver surgery: an atlas. Springer, BerlinCrossRef
17.
go back to reference Donadon M, Costa G, Cimino M et al (2016) Diagnosis and management of bile leaks after hepatectomy: results of a prospective analysis of 475 hepatectomies. World J Surg 40:172–181CrossRefPubMed Donadon M, Costa G, Cimino M et al (2016) Diagnosis and management of bile leaks after hepatectomy: results of a prospective analysis of 475 hepatectomies. World J Surg 40:172–181CrossRefPubMed
18.
go back to reference Groenwold RH, Hak E, Hoes AW (2009) Quantitative assessment of unobserved confounding is mandatory in nonrandomized intervention studies. J Clin Epidemiol 62:22–28CrossRefPubMed Groenwold RH, Hak E, Hoes AW (2009) Quantitative assessment of unobserved confounding is mandatory in nonrandomized intervention studies. J Clin Epidemiol 62:22–28CrossRefPubMed
19.
go back to reference Copas JB (1983) Regression, prediction and shrinkage. J R Stat Soc 45:311–354 Copas JB (1983) Regression, prediction and shrinkage. J R Stat Soc 45:311–354
20.
go back to reference Peduzzi P, Concato J, Feinstein AR et al (1995) Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol 48:1503–1510CrossRefPubMed Peduzzi P, Concato J, Feinstein AR et al (1995) Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol 48:1503–1510CrossRefPubMed
21.
go back to reference Malinchoc M, Kamath PS, Gordon FD et al (2000) A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31:864–871CrossRefPubMed Malinchoc M, Kamath PS, Gordon FD et al (2000) A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31:864–871CrossRefPubMed
22.
go back to reference Yin L, Li H, Li AJ et al (2014) Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT. J Hepatol 61:82–88CrossRefPubMed Yin L, Li H, Li AJ et al (2014) Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT. J Hepatol 61:82–88CrossRefPubMed
23.
go back to reference Zhong JH, Xiang BD, Gong WF et al (2013) Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization. PLoS One 8:e68193CrossRefPubMedPubMedCentral Zhong JH, Xiang BD, Gong WF et al (2013) Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization. PLoS One 8:e68193CrossRefPubMedPubMedCentral
24.
25.
go back to reference Farinati F, Vanin V, Giacomin A et al (2015) BCLC stage B hepatocellular carcinoma and transcatheter arterial chemoembolization: a 20-year survey by the Italian Liver Cancer group. Liver Int 35:223–231CrossRefPubMed Farinati F, Vanin V, Giacomin A et al (2015) BCLC stage B hepatocellular carcinoma and transcatheter arterial chemoembolization: a 20-year survey by the Italian Liver Cancer group. Liver Int 35:223–231CrossRefPubMed
26.
go back to reference Yang XD, Pan LH, Wang L et al (2015) Systematic review of single large and/or multinodular hepatocellular carcinoma: surgical resection improves survival. Asian Pac J Cancer Prev 16:5541–5547CrossRefPubMed Yang XD, Pan LH, Wang L et al (2015) Systematic review of single large and/or multinodular hepatocellular carcinoma: surgical resection improves survival. Asian Pac J Cancer Prev 16:5541–5547CrossRefPubMed
27.
go back to reference Qi X, Wang D, Su C et al (2015) Hepatic resection versus transarterial chemoembolization for the initial treatment of hepatocellular carcinoma: a systematic review and meta-analysis. Oncotarget 6:18715–18733PubMedPubMedCentral Qi X, Wang D, Su C et al (2015) Hepatic resection versus transarterial chemoembolization for the initial treatment of hepatocellular carcinoma: a systematic review and meta-analysis. Oncotarget 6:18715–18733PubMedPubMedCentral
28.
go back to reference Kapitanov T, Neumann UP, Schmeding M (2015) Hepatocellular carcinoma in liver cirrhosis: surgical resection versus transarterial chemoembolization—a meta-analysis. Gastroenterol Res Pract 2015:696120CrossRefPubMedPubMedCentral Kapitanov T, Neumann UP, Schmeding M (2015) Hepatocellular carcinoma in liver cirrhosis: surgical resection versus transarterial chemoembolization—a meta-analysis. Gastroenterol Res Pract 2015:696120CrossRefPubMedPubMedCentral
29.
go back to reference Vitale A, Burra P, Frigo AC et al (2015) Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona clinic liver cancer stages: a multicentre study. J Hepatol 62:617–624CrossRefPubMed Vitale A, Burra P, Frigo AC et al (2015) Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona clinic liver cancer stages: a multicentre study. J Hepatol 62:617–624CrossRefPubMed
30.
go back to reference Jianyong L, Lunan Y, Wentao W et al (2014) Barcelona clinic liver cancer stage B hepatocellular carcinoma: transarterial chemoembolization or hepatic resection? Medicine (Baltimore) 93:e180CrossRef Jianyong L, Lunan Y, Wentao W et al (2014) Barcelona clinic liver cancer stage B hepatocellular carcinoma: transarterial chemoembolization or hepatic resection? Medicine (Baltimore) 93:e180CrossRef
31.
go back to reference Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171CrossRefPubMed Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171CrossRefPubMed
32.
go back to reference Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734–1739CrossRefPubMed Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734–1739CrossRefPubMed
33.
go back to reference Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442CrossRefPubMed Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442CrossRefPubMed
34.
go back to reference Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25CrossRefPubMed Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25CrossRefPubMed
35.
go back to reference Camma C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224:47–54CrossRefPubMed Camma C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224:47–54CrossRefPubMed
36.
go back to reference Torzilli G, Makuuchi M, Inoue K 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 134:984–992CrossRefPubMed Torzilli G, Makuuchi M, Inoue K 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 134:984–992CrossRefPubMed
37.
go back to reference Ng KK, Vauthey JN, Pawlik TM et al (2005) Is hepatic resection for large or multinodular hepatocellular carcinoma justified? Results from a multi-institutional database. Ann Surg Oncol 12:364–373CrossRefPubMed Ng KK, Vauthey JN, Pawlik TM et al (2005) Is hepatic resection for large or multinodular hepatocellular carcinoma justified? Results from a multi-institutional database. Ann Surg Oncol 12:364–373CrossRefPubMed
38.
go back to reference Sangro B, Carpanese L, Cianni R et al (2011) Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 54:868–878CrossRefPubMed Sangro B, Carpanese L, Cianni R et al (2011) Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 54:868–878CrossRefPubMed
39.
go back to reference Mazzaferro V, Sposito C, Bhoori S et al (2013) Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 57:1826–1837CrossRefPubMed Mazzaferro V, Sposito C, Bhoori S et al (2013) Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 57:1826–1837CrossRefPubMed
40.
go back to reference Cucchetti A, Mazzaferro V, Pinna AD et al (2017) Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma. Br J Surg 104:1704–1712CrossRefPubMed Cucchetti A, Mazzaferro V, Pinna AD et al (2017) Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma. Br J Surg 104:1704–1712CrossRefPubMed
41.
go back to reference Giuliante F, Ardito F, Pinna AD et al (2012) Liver resection for hepatocellular carcinoma ≤ 3 cm: results of an Italian Multicenter Study on 588 patients. J Am Coll Surg 215:244–254CrossRefPubMed Giuliante F, Ardito F, Pinna AD et al (2012) Liver resection for hepatocellular carcinoma ≤ 3 cm: results of an Italian Multicenter Study on 588 patients. J Am Coll Surg 215:244–254CrossRefPubMed
42.
go back to reference Bruix J, Takayama T, Mazzaferro V et al (2015) Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 16:1344–1354CrossRefPubMed Bruix J, Takayama T, Mazzaferro V et al (2015) Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 16:1344–1354CrossRefPubMed
43.
go back to reference Bolondi L, Burroughs A, Dufour JF et al (2012) Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis 32:348–359PubMed Bolondi L, Burroughs A, Dufour JF et al (2012) Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis 32:348–359PubMed
44.
go back to reference Weinmann A, Koch S, Sprinzl M et al (2015) Survival analysis of proposed BCLC-B subgroups in hepatocellular carcinoma patients. Liver Int 35:591–600CrossRefPubMed Weinmann A, Koch S, Sprinzl M et al (2015) Survival analysis of proposed BCLC-B subgroups in hepatocellular carcinoma patients. Liver Int 35:591–600CrossRefPubMed
Metadata
Title
Dissecting the multinodular hepatocellular carcinoma subset: is there a survival benefit after hepatectomy?
Authors
Matteo Donadon
Andrea Fontana
Fabio Procopio
Daniele Del Fabbro
Matteo Cimino
Luca Viganò
Angela Palmisano
Guido Torzilli
Publication date
01-03-2019
Publisher
Springer International Publishing
Published in
Updates in Surgery / Issue 1/2019
Print ISSN: 2038-131X
Electronic ISSN: 2038-3312
DOI
https://doi.org/10.1007/s13304-019-00626-3

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