Perioperative Lymphopenia is Associated with Increased Risk of Recurrence and Worse Survival Following Hepatectomy for Hepatocellular Carcinoma

Diamantis I Tsilimigras; Yutaka Endo; Francesca Ratti; Hugo P Marques; François Cauchy; Vincent Lam; George A Poultsides; Irinel Popescu; Sorin Alexandrescu; Guillaume Martel; Minoru Kitago; Alfredo Guglielmi; Tom Hugh; Luca Aldrighetti; Ana Gleisner; Feng Shen; Itaru Endo; Timothy M Pawlik

doi:10.1245/s10434-023-14811-7

Perioperative Lymphopenia is Associated with Increased Risk of Recurrence and Worse Survival Following Hepatectomy for Hepatocellular Carcinoma

Ann Surg Oncol. 2024 Apr;31(4):2568-2578. doi: 10.1245/s10434-023-14811-7. Epub 2024 Jan 5.

Authors

Diamantis I Tsilimigras¹, Yutaka Endo¹, Francesca Ratti², Hugo P Marques³, François Cauchy⁴, Vincent Lam⁵, George A Poultsides⁶, Irinel Popescu⁷, Sorin Alexandrescu⁷, Guillaume Martel⁸, Minoru Kitago⁹, Alfredo Guglielmi¹⁰, Tom Hugh¹¹, Luca Aldrighetti², Ana Gleisner¹², Feng Shen¹³, Itaru Endo¹⁴, Timothy M Pawlik¹⁵

Affiliations

¹ Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
² Department of Surgery, Ospedale San Raffaele, Milan, Italy.
³ Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal.
⁴ Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France.
⁵ Department of Surgery, Westmead Hospital, Sydney, NSW, Australia.
⁶ Department of Surgery, Stanford University, Stanford, CA, USA.
⁷ Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania.
⁸ Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
⁹ Department of Surgery, Keio University, Tokyo, Japan.
¹⁰ Department of Surgery, University of Verona, Verona, Italy.
¹¹ Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia.
¹² Department of Surgery, University of Colorado, Denver, CO, USA.
¹³ Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
¹⁴ Yokohama City University School of Medicine, Yokohama, Japan.
¹⁵ Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. tim.pawlik@osumc.edu.

PMID: 38180707
DOI: 10.1245/s10434-023-14811-7

Abstract

Introduction: Immune dysregulation may be associated with cancer progression. We sought to investigate the prognostic value of perioperative lymphopenia on short- and long-term outcomes among patients undergoing resection of hepatocellular carcinoma (HCC).

Methods: Patients undergoing resection of HCC between 2000 and 2020 were identified using an international database. The incidence and impact of perioperative lymphopenia [preoperative, postoperative day (POD) 1/3/5], defined as absolute lymphocyte count (ALC) <1000/μL, on short- and long-term outcomes was assessed.

Results: Among 1448 patients, median preoperative ALC was 1593/μL [interquartile range (IQR) 1208-2006]. The incidence of preoperative lymphopenia was 14.0%, and 50.2%, 45.1% and 35.6% on POD1, POD3 and POD5, respectively. Preoperative lymphopenia predicted 5-year overall survival (OS) [lymphopenia vs. no lymphopenia: 49.1% vs. 66.1%] and 5-year disease-free survival (DFS) [25.0% vs. 41.5%] (both p < 0.05). Lymphopenia on POD1 (5-year OS: 57.1% vs. 71.2%; 5-year DFS: 30.0% vs. 41.1%), POD3 (5-year OS: 57.3% vs. 68.9%; 5-year DFS: 35.4% vs. 42.7%), and POD5 (5-year OS: 53.1% vs. 66.1%; 5-year DFS: 32.8% vs. 42.3%) was associated with worse long-term outcomes (all p < 0.05). Patients with severe lymphopenia (ALC <500/μL) on POD5 had worse 5-year OS and DFS (5-year OS: 44.7% vs. 54.3% vs. 66.1%; 5-year DFS: 27.8% vs. 33.3% vs. 42.3%) [both p < 0.05], as well as higher incidence of overall (45.5% vs. 25.3% vs. 30.9%; p = 0.013) and major complications (18.2% vs. 3.4% vs. 4.5%; p < 0.001) versus individuals with moderate (ALC 500-1000/μL) or no lymphopenia following hepatectomy for HCC. After adjusting for competing risk factors, prolonged lymphopenia was independently associated with higher hazards of death [hazard ratio (HR) 1.38, 95% CI 1.11-1.72] and recurrence (HR 1.22, 95% CI 1.02-1.45).

Conclusion: Perioperative lymphopenia had short- and long-term prognostic implications among individuals undergoing hepatectomy for HCC.

Keywords: HCC; Lymphopenia; Resection; Surgery; Survival.

MeSH terms

Carcinoma, Hepatocellular* / pathology
Disease-Free Survival
Hepatectomy / adverse effects
Humans
Liver Neoplasms* / pathology
Lymphopenia* / etiology
Prognosis
Retrospective Studies