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Published in: Journal of Gastrointestinal Surgery 7/2020

01-07-2020 | Hepatocellular Carcinoma | Original Article

Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: An International Multi-Institutional Analysis

Authors: Diamantis I. Tsilimigras, Kota Sahara, Dimitrios Moris, J. Madison Hyer, Anghela Z. Paredes, Fabio Bagante, Katiuscha Merath, Ayesha S. Farooq, Francesca Ratti, Hugo P. Marques, Olivier Soubrane, Daniel Azoulay, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Alfredo Guglielmi, Tom Hugh, Luca Aldrighetti, Itaru Endo, Timothy M. Pawlik

Published in: Journal of Gastrointestinal Surgery | Issue 7/2020

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Abstract

Introduction

Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (> 1 cm) versus narrow (< 1 cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy.

Methods

Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins.

Results

Among 404 patients, median patient age was 66 years (IQR: 58–73). Most patients (n = 326, 80.7%) had surgical margin < 1 cm, while 78 (19.3%) patients had a > 1 cm margin. The majority of patients had early recurrences (< 24 months) in both margin width groups (< 1 cm: 70.3% vs > 1 cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic (< 1 cm: 77% vs > 1 cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin < 1 cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin > 1 cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: < 1 cm: 49.2% vs > 1 cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width > 1 cm was associated with a better 3-year RFS compared to margin < 1 cm (86.7% vs 47.3%, p = 0.017). On multivariable analysis, margin > 1 cm remained protective against recurrence (HR = 0.50, 95%CI 0.28–0.89), whereas Child-Pugh B (HR = 2.13, 95%CI 1.09–4.15), AFP > 20 ng/mL (HR = 1.71, 95%CI 1.18–2.48), and presence of microscopic lymphovascular invasion (HR = 1.48, 95%CI 1.01–2.18) were associated with a higher hazard of recurrence.

Conclusion

Resection margins > 1 cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5 cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.
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Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.CrossRef Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.CrossRef
2.
go back to reference Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology 2015;61:191–9.CrossRef Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology 2015;61:191–9.CrossRef
3.
go back to reference European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182–236.CrossRef European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182–236.CrossRef
4.
go back to reference Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723–50.CrossRef Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723–50.CrossRef
5.
go back to reference Lee JW, Lee YJ, Park KM, Hwang DW, Lee JH, Song KB. Anatomical Resection But Not Surgical Margin Width Influence Survival Following Resection for HCC, A Propensity Score Analysis. World J Surg 2016;40:1429–39.CrossRef Lee JW, Lee YJ, Park KM, Hwang DW, Lee JH, Song KB. Anatomical Resection But Not Surgical Margin Width Influence Survival Following Resection for HCC, A Propensity Score Analysis. World J Surg 2016;40:1429–39.CrossRef
6.
go back to reference Chau GY, Lui WY, Tsay SH, et al. Prognostic significance of surgical margin in hepatocellular carcinoma resection: an analysis of 165 Childs’ A patients. J Surg Oncol 1997;66:122–6.CrossRef Chau GY, Lui WY, Tsay SH, et al. Prognostic significance of surgical margin in hepatocellular carcinoma resection: an analysis of 165 Childs’ A patients. J Surg Oncol 1997;66:122–6.CrossRef
7.
go back to reference Chen MF, Tsai HP, Jeng LB, et al. Prognostic factors after resection for hepatocellular carcinoma in noncirrhotic livers: univariate and multivariate analysis. World J Surg 2003;27:443–7.CrossRef Chen MF, Tsai HP, Jeng LB, et al. Prognostic factors after resection for hepatocellular carcinoma in noncirrhotic livers: univariate and multivariate analysis. World J Surg 2003;27:443–7.CrossRef
8.
go back to reference Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg 2007;245:36–43.CrossRef Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg 2007;245:36–43.CrossRef
9.
go back to reference Lazzara C, Navarra G, Lazzara S, et al. Does the margin width influence recurrence rate in liver surgery for hepatocellular carcinoma smaller than 5 cm? Eur Rev Med Pharmacol Sci 2017;21:523–9.PubMed Lazzara C, Navarra G, Lazzara S, et al. Does the margin width influence recurrence rate in liver surgery for hepatocellular carcinoma smaller than 5 cm? Eur Rev Med Pharmacol Sci 2017;21:523–9.PubMed
10.
go back to reference Zhong FP, Zhang YJ, Liu Y, Zou SB. Prognostic impact of surgical margin in patients with hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2017;96:e8043.CrossRef Zhong FP, Zhang YJ, Liu Y, Zou SB. Prognostic impact of surgical margin in patients with hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2017;96:e8043.CrossRef
11.
go back to reference Sakon M, Nagano H, Nakamori S, et al. Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics. Arch Surg 2002;137:94–9.CrossRef Sakon M, Nagano H, Nakamori S, et al. Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics. Arch Surg 2002;137:94–9.CrossRef
12.
go back to reference Famularo S, Di Sandro S, Giani A, et al. Recurrence Patterns After Anatomic or Parenchyma-Sparing Liver Resection for Hepatocarcinoma in a Western Population of Cirrhotic Patients. Ann Surg Oncol 2018;25:3974–81.CrossRef Famularo S, Di Sandro S, Giani A, et al. Recurrence Patterns After Anatomic or Parenchyma-Sparing Liver Resection for Hepatocarcinoma in a Western Population of Cirrhotic Patients. Ann Surg Oncol 2018;25:3974–81.CrossRef
13.
go back to reference Kumar AM, Fredman ET, Coppa C, El-Gazzaz G, Aucejo FN, Abdel-Wahab M. Patterns of cancer recurrence in localized resected hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2015;14:269–75.CrossRef Kumar AM, Fredman ET, Coppa C, El-Gazzaz G, Aucejo FN, Abdel-Wahab M. Patterns of cancer recurrence in localized resected hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2015;14:269–75.CrossRef
14.
go back to reference Lee KT, Wang SN, Su RW, et al. Is wider surgical margin justified for better clinical outcomes in patients with resectable hepatocellular carcinoma? J Formos Med Assoc 2012;111:160–70.CrossRef Lee KT, Wang SN, Su RW, et al. Is wider surgical margin justified for better clinical outcomes in patients with resectable hepatocellular carcinoma? J Formos Med Assoc 2012;111:160–70.CrossRef
15.
go back to reference Lafaro K, Grandhi MS, Herman JM, Pawlik TM. The importance of surgical margins in primary malignancies of the liver. J Surg Oncol 2016;113:296–303.CrossRef Lafaro K, Grandhi MS, Herman JM, Pawlik TM. The importance of surgical margins in primary malignancies of the liver. J Surg Oncol 2016;113:296–303.CrossRef
16.
go back to reference Field WBS, Rostas JW, Philps P, Scoggins CR, McMasters KM, Martin RCG, II. Wide versus narrow margins after partial hepatectomy for hepatocellular carcinoma: Balancing recurrence risk and liver function. Am J Surg 2017;214:273–7.CrossRef Field WBS, Rostas JW, Philps P, Scoggins CR, McMasters KM, Martin RCG, II. Wide versus narrow margins after partial hepatectomy for hepatocellular carcinoma: Balancing recurrence risk and liver function. Am J Surg 2017;214:273–7.CrossRef
17.
go back to reference Spolverato G, Yakoob MY, Kim Y, et al. The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2015;22:4020–8.CrossRef Spolverato G, Yakoob MY, Kim Y, et al. The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2015;22:4020–8.CrossRef
18.
go back to reference Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. J Gastrointest Surg 2007;11:1478–86; discussion 86-7.CrossRef Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. J Gastrointest Surg 2007;11:1478–86; discussion 86-7.CrossRef
19.
go back to reference Dong S, Wang Z, Wu L, Qu Z. Effect of surgical margin in R0 hepatectomy on recurrence-free survival of patients with solitary hepatocellular carcinomas without macroscopic vascular invasion. Medicine (Baltimore) 2016;95:e5251.CrossRef Dong S, Wang Z, Wu L, Qu Z. Effect of surgical margin in R0 hepatectomy on recurrence-free survival of patients with solitary hepatocellular carcinomas without macroscopic vascular invasion. Medicine (Baltimore) 2016;95:e5251.CrossRef
20.
go back to reference Moris D, Rahnemai-Azar AA, Tsilimigras DI, et al. Updates and Critical Insights on Glissonian Approach in Liver Surgery. J Gastrointest Surg 2018;22:154–63.CrossRef Moris D, Rahnemai-Azar AA, Tsilimigras DI, et al. Updates and Critical Insights on Glissonian Approach in Liver Surgery. J Gastrointest Surg 2018;22:154–63.CrossRef
21.
go back to reference Moris D, Tsilimigras DI, Kostakis ID, et al. Anatomic versus non-anatomic resection for hepatocellular carcinoma: A systematic review and meta-analysis. Eur J Surg Oncol 2018;44:927–38.CrossRef Moris D, Tsilimigras DI, Kostakis ID, et al. Anatomic versus non-anatomic resection for hepatocellular carcinoma: A systematic review and meta-analysis. Eur J Surg Oncol 2018;44:927–38.CrossRef
22.
go back to reference Goh BK, Chow PK, Teo JY, et al. Number of nodules, Child-Pugh status, margin positivity, and microvascular invasion, but not tumor size, are prognostic factors of survival after liver resection for multifocal hepatocellular carcinoma. J Gastrointest Surg 2014;18:1477–85.CrossRef Goh BK, Chow PK, Teo JY, et al. Number of nodules, Child-Pugh status, margin positivity, and microvascular invasion, but not tumor size, are prognostic factors of survival after liver resection for multifocal hepatocellular carcinoma. J Gastrointest Surg 2014;18:1477–85.CrossRef
23.
go back to reference Hanazaki K, Kajikawa S, Shimozawa N, et al. Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma. J Am Coll Surg 2000;191:381–8.CrossRef Hanazaki K, Kajikawa S, Shimozawa N, et al. Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma. J Am Coll Surg 2000;191:381–8.CrossRef
24.
go back to reference Moris D, Chakedis J, Sun SH, et al. Management, outcomes, and prognostic factors of ruptured hepatocellular carcinoma: A systematic review. J Surg Oncol 2018;117:341–53.CrossRef Moris D, Chakedis J, Sun SH, et al. Management, outcomes, and prognostic factors of ruptured hepatocellular carcinoma: A systematic review. J Surg Oncol 2018;117:341–53.CrossRef
25.
go back to reference Notarpaolo A, Layese R, Magistri P, et al. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol 2017;66:552–9.CrossRef Notarpaolo A, Layese R, Magistri P, et al. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol 2017;66:552–9.CrossRef
26.
go back to reference Cloyd JM, Pawlik TM. Adjuvant Therapy for Biliary Tract Cancers: New Evidence to Resolve Old Questions. J Oncol Pract 2018;14:723–4.CrossRef Cloyd JM, Pawlik TM. Adjuvant Therapy for Biliary Tract Cancers: New Evidence to Resolve Old Questions. J Oncol Pract 2018;14:723–4.CrossRef
27.
go back to reference Zhou L, Rui JA, Wang SB, Chen SG, Qu Q. Early recurrence in large hepatocellular carcinoma after curative hepatic resection: prognostic significance and risk factors. Hepatogastroenterology 2014;61:2035–41.PubMed Zhou L, Rui JA, Wang SB, Chen SG, Qu Q. Early recurrence in large hepatocellular carcinoma after curative hepatic resection: prognostic significance and risk factors. Hepatogastroenterology 2014;61:2035–41.PubMed
28.
go back to reference Wang Z, Luo L, Cheng Y, et al. Correlation Between Postoperative Early Recurrence of Hepatocellular Carcinoma and Mesenchymal Circulating Tumor Cells in Peripheral Blood. J Gastrointest Surg 2018;22:633–9.CrossRef Wang Z, Luo L, Cheng Y, et al. Correlation Between Postoperative Early Recurrence of Hepatocellular Carcinoma and Mesenchymal Circulating Tumor Cells in Peripheral Blood. J Gastrointest Surg 2018;22:633–9.CrossRef
Metadata
Title
Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: An International Multi-Institutional Analysis
Authors
Diamantis I. Tsilimigras
Kota Sahara
Dimitrios Moris
J. Madison Hyer
Anghela Z. Paredes
Fabio Bagante
Katiuscha Merath
Ayesha S. Farooq
Francesca Ratti
Hugo P. Marques
Olivier Soubrane
Daniel Azoulay
Vincent Lam
George A. Poultsides
Irinel Popescu
Sorin Alexandrescu
Guillaume Martel
Alfredo Guglielmi
Tom Hugh
Luca Aldrighetti
Itaru Endo
Timothy M. Pawlik
Publication date
01-07-2020
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 7/2020
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-019-04275-0

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