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Impact of margin status on long-term results of liver resection for hepatocellular carcinoma: single-center time-to-recurrence analysis

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Abstract

Occult metastasis from the initial tumor and a de novo second primary hepatocellular carcinoma (HCC) were recognized as the main causes for the onset of early and late HCC recurrence, after liver resection (LR). This study aims to compare the time to recurrence after LR for HCC in which a margin ≤ 1 mm or > 1 mm was achieved. A single-center retrospective study involving 256 patients was conducted from June 2005 to June 2019. HCC patients resected with a radical surgical approach were investigated and stratified into groups A (resection margins ≤ 1 mm) and B (> 1 mm), as measured on final pathologic assessment. Kaplan–Meier estimators were used to estimate the probability of recurrence, and the log-rank test was used to compare groups. Uni- and multivariable (stepwise) Cox regression models were used to assess the effect of several HCC pathological characteristics. Twenty patients were excluded for the presence of microscopic tumor invasion at pathologic analysis (R1); 236 patients underwent radical (R0) LR, and were included in the study and divided into group A (n = 61, 26%), and group B (n = 175, 74%). No differences between the two groups were detected regarding: epidemiology, tumor characteristics, type of LR, and follow-up. The estimated probability of recurrence for group A and group B at 12 and 24 months was 27% and 38%, and, 33% and 46%, respectively. Univariate and multivariable Cox regression model estimates showed that tumor grading (HR 2.1, 95% CI 1.2–3.4, p = 0.006), number of nodules (HR 1.2, 95% CI 1.0–1.4, p = 0.015), and extension of the resection (HR 1.8, 95% CI 1.0–1.1, p = 0.047) were independent risk factors for HCC recurrence, with no significant effect of margin status on time to recurrence. A R0 approach that considers a margin of resection > 1 mm does not improve the likelihood of HCC recurrence. Otherwise, our experience confirms that biologic tumor characteristics are the principal factors predictive of local and systemic recurrence.

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Abbreviations

AFP:

Alpha-fetoprotein

BCLC:

Barcelona clinic liver cancer

CI:

Confidence interval

CT:

Computed tomography

HCC:

Hepatocellular carcinoma

HR:

Hazard ratio

INR:

International normalized ratio

IQR:

Inter-quartile range

PHT:

Portal hypertension

LR:

Liver resection

LT:

Liver transplantation

RECIST:

Response evaluation criteria in solid tumors

TACE:

Transarterial chemoembolization

TTR:

Time to recurrence

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Authors and Affiliations

  1. Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy

    Salvatore Gruttadauria, Duilio Pagano, Lidia R. Corsini, Davide Cintorino, Sergio Li Petri, Sergio Calamia, Aurelio Seidita & Fabrizio di Francesco

  2. Department of Surgery, University of Catania, Catania, Italy

    Salvatore Gruttadauria

  3. Department of Oncology, A.O.U.P. P. Giaccone, Palermo, Italy

    Lidia R. Corsini

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  1. Salvatore Gruttadauria
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Contributions

SG: critical revision of article, approval of article. DP, LRC, DC, SLP, SC, AS, and FdiF: concept/design, data analysis/interpretation, and drafting article.

Corresponding author

Correspondence to Salvatore Gruttadauria.

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The authors of this manuscript have no conflicts of interest, as described by this journal, to disclose. This manuscript has not been published, and is not under consideration elsewhere. We declare that all authors are in agreement on the content of the manuscript and have no potential conflicts of interest. We have nothing to disclose regarding sources of support in the form of grants, equipment, and/or pharmaceuticals.

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Gruttadauria, S., Pagano, D., Corsini, L.R. et al. Impact of margin status on long-term results of liver resection for hepatocellular carcinoma: single-center time-to-recurrence analysis. Updates Surg 72, 109–117 (2020). https://doi.org/10.1007/s13304-019-00686-5

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