Pardolesi A, Ferrari M, Leuzzi G, Ceruti E, Cioffi U, De Simone M, Cioffi G, Solli P. Pulmonary metastasectomy for recurrent hepatocellular carcinoma after liver transplantation: A therapeutic challenge. World J Gastrointest Surg 2026; 18(9): 121591 [DOI: 10.4240/wjgs.121591]
Corresponding Author of This Article
Michele Ferrari, MD, Department of Thoracic Surgery, Istituto Nazionale Tumori, Via G.Venezian 1, Milan 20133, Lombardy, Italy. michele.ferrari@istitutotumori.mi.it
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Surgery
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review-article
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Pardolesi A, Ferrari M, Leuzzi G, Ceruti E, Cioffi U, De Simone M, Cioffi G, Solli P. Pulmonary metastasectomy for recurrent hepatocellular carcinoma after liver transplantation: A therapeutic challenge. World J Gastrointest Surg 2026; 18(9): 121591 [DOI: 10.4240/wjgs.121591]
World J Gastrointest Surg. Sep 27, 2026; 18(9): 121591 Published online Sep 27, 2026. doi: 10.4240/wjgs.121591
Pulmonary metastasectomy for recurrent hepatocellular carcinoma after liver transplantation: A therapeutic challenge
Alessandro Pardolesi, Michele Ferrari, Giovanni Leuzzi, Edoardo Ceruti, Ugo Cioffi, Matilde De Simone, Gerardo Cioffi, Piergiorgio Solli
Alessandro Pardolesi, Michele Ferrari, Giovanni Leuzzi, Piergiorgio Solli, Department of Thoracic Surgery, Istituto Nazionale Tumori, Milan 20133, Lombardy, Italy
Edoardo Ceruti, Division of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Lombardy, Italy
Ugo Cioffi, Matilde De Simone, Department of Surgery, University of Milan, Milan 20122, Lombardy, Italy
Gerardo Cioffi, Department of Sciences and Technologies, UniSannio, Benevento 82100, Campania, Italy
Co-first authors: Alessandro Pardolesi and Michele Ferrari.
Author contributions: Pardolesi A and Ferrari M contributed equally to this manuscript as co-first authors; Pardolesi A, Ferrari M, Leuzzi G, Ceruti E, Cioffi U, De Simone M, Cioffi G, and Solli P contributed to research and revised the manuscript, read and accepted the final version.
AI contribution statement: No AI tools, including ChatGPT or similar technologies, were used in the preparation of this manuscript. All aspects of the work, including data generation, analysis, interpretation, and writing, were performed solely by the authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Michele Ferrari, MD, Department of Thoracic Surgery, Istituto Nazionale Tumori, Via G.Venezian 1, Milan 20133, Lombardy, Italy. michele.ferrari@istitutotumori.mi.it
Received: March 31, 2026 Revised: May 12, 2026 Accepted: June 16, 2026 Published online: September 27, 2026 Processing time: 171 Days and 22.4 Hours
Abstract
Recurrence of hepatocellular carcinoma remains the leading cause of mortality after liver transplantation (LT), with the lungs representing the most frequent extrahepatic site. This review evaluates the role of pulmonary metastasectomy in carefully selected LT recipients, with a focus on patient selection criteria, surgical indications, and multimodal treatment strategies. A scoping review was conducted using the PubMed database. The search incorporated the following terms: “hepatocellular carcinoma”, “pulmonary metastasectomy”, “liver transplantation”, “recurrence”, and “tumor biology”. Studies published in English from 2005 onward were included if they specifically addressed pulmonary metastases in post-LT patients. Non-transplant populations and non-English articles were excluded. Studies were selected based on their relevance to the topic. Evidence, primarily from small retrospective series, supports pulmonary metastasectomy in highly selected patients with lung-limited disease. Favorable prognostic factors include a disease-free interval exceeding 12 months, low or normal alpha-fetoprotein levels, and limited metastatic burden. Reported 5-year overall survival rates range from 33% to 43%, indicating a potential survival benefit in appropriately selected cases. Pulmonary metastasectomy offers a valuable therapeutic option for LT recipients with resectable, lung-confined recurrence and favorable tumor biology. For unresectable or disseminated disease, alternative strategies including locoregional and systemic therapy should be pursued within a multidisciplinary framework.
Core Tip: Liver transplantation is a definitive treatment for hepatocellular carcinoma, yet recurrence occurs 8%-20% of patients, with the lung being the most common extra-hepatic site. Pulmonary metastasectomy offers meaningful survival benefit in carefully selected patients with resectable, lung-limited disease and favorable tumor biology. Patient selection should prioritize disease-free survival, alpha-fetoprotein levels, and oligometastatic pattern, rather than immunosuppression management alone. We emphasize the need for rigorous, biology-driven selection criteria and prospective studies to define the role of surgery within a multimodal approach to extra-hepatic hepatocellular carcinoma recurrence.
