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Cancers
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Surgical and Non-Surgical Convergence in Hepatocellular Carcinoma
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Surgical and Non-Surgical Convergence in Hepatocellular Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 1782

Special Issue Editor

Dr. Alessandro Vitale

E-Mail Website
Guest Editor
Hepatobiliary and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padova, Italy
Interests: hepatocellular carcinoma; multiparametric therapeutic hierarchy; conversion therapy; liver transplantation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) remains a significant global health burden, with 866,136 new cases and a mortality-to-incidence ratio of 0.86 reported in 2022. Primarily caused by liver cirrhosis, HCC is increasingly linked to non-viral causes, particularly metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. While liver transplantation and resection continue to be the main curative options, the past decade has seen notable advances in non-surgical treatments—including ablation, transarterial therapies, and systemic treatments—that have transformed the therapeutic landscape.

Instead of being seen as alternative or competing options, these treatments are increasingly regarded within integrative frameworks, such as the Multiparametric and Converse Therapeutic Hierarchies, where combined and sequential strategies reveal curative possibilities that were once considered unreachable.

This special issue invites original research, high-quality reviews, and translational perspectives that challenge traditional staging and treatment paradigms while exploring the integration of surgical and non-surgical approaches in HCC. Special focus will be on studies addressing downstaging, curative conversion, therapeutic stage migration, and multiparametric/multidisciplinary decision-making approaches.

By bringing together work at the forefront of integrated HCC management, this issue strives to define a future where therapeutic boundaries are flexible, personalised for patients, and focused on maximising survival and potential for cure.

Dr. Alessandro Vitale
Guest Editor

Marco Brolese
Ilaria Govoni
Virginia Padoan
Guest Editor Assistants

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatocellular carcinoma
  • conversion therapy
  • HCC treatment boundaries
  • surgical–non-surgical convergence
  • multidisciplinary HCC management

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Published Papers (2 papers)

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Research

20 pages, 1881 KB  
Article
Modified Charlson Comorbidity Index to Improve Management of Patients with Hepatocellular Carcinoma: A Step Towards Multiparametric Approach
by Eleonora Alimenti, Massimo Iavarone, Elia Fracas, Lorenzo Canova, Mariangela Bruccoleri, Barbara Antonelli, Anna Maria Ierardi, Pierpaolo Biondetti, Angelo Sangiovanni, Cristiano Quintini, Gianpaolo Carrafiello and Pietro Lampertico
Cancers 2026, 18(7), 1151; https://doi.org/10.3390/cancers18071151 - 2 Apr 2026
Viewed by 653
Abstract
Background and aims: Hepatocellular carcinoma (HCC) patients frequently present with comorbidities that limit therapeutic options and increase mortality. This study evaluated the performance of the Charlson Comorbidity Index (CCI) and a modified CCI (mCCI) in stratifying patients with HCC to predict treatment allocation [...] Read more.
Background and aims: Hepatocellular carcinoma (HCC) patients frequently present with comorbidities that limit therapeutic options and increase mortality. This study evaluated the performance of the Charlson Comorbidity Index (CCI) and a modified CCI (mCCI) in stratifying patients with HCC to predict treatment allocation and survival. Methods: A retrospective single-center cohort study analyzed 401 patients with de novo HCC (74% male, median age 68 years, 80% Child–Pugh-Turcotte (CPT) A, 65% viral etiology, 70% Barcelona Clinic Liver Cancer stage (BCLC) 0/A). CCI and mCCI (with points related to HCC and chronic liver disease excluded), were calculated at diagnosis for each patient. The primary endpoint was overall survival (OS) estimated by Kaplan–Meier method and compared across mCCI classes; Cox uni/multivariable models were applied to identify predictors of mortality. The secondary aim was evaluating the association between mCCI and treatment allocation. Results: While CCI classified 94% of patients as “high-risk”, mCCI reclassified patients into “high-risk” (21%), “intermediate-risk” (48%), and “low-risk” (31%), demonstrating better stratification whilst maintaining a strong correlation with CCI (Kendall’s tau-b = 0.57, p < 0.001). BCLC B patients with “high-risk” mCCI exhibited significantly lower access to first-line curative treatment (14% vs. 47%, p = 0.03). Moreover, “high” or “intermediate-risk” patients according to mCCI experienced significantly shorter OS compared to “low-risk” (median OS 36 vs. 49 vs. 74 months, p < 0.001). “High-risk” and “intermediate-risk” mCCI classes were independent predictors of mortality, alongside alpha-fetoprotein, CPT and BCLC stage. Considering the items composing mCCI, age and cardiovascular diseases were independent predictors of mortality. Conclusions: mCCI provides a more accurate assessment of comorbidities than the standard CCI and is associated with survival, hence it can contribute to designing patient-tailored therapeutic strategies. Full article
(This article belongs to the Special Issue Surgical and Non-Surgical Convergence in Hepatocellular Carcinoma)
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14 pages, 563 KB  
Article
The Predictive Role of [18F]FDG PET/CT in Early HCC Recurrence After Liver Transplantation
by Eleonora Alimenti, Lorenzo Canova, Massimo Iavarone, Giovanni Aldinio, Daniele Dondossola, Luigia Florimonte, Eloisa Franchi, Giulia Marini, Clara Dibenedetto, Lucio Caccamo, Federica Cerini, Massimo Castellani, Cristiano Quintini and Pietro Lampertico
Cancers 2026, 18(4), 555; https://doi.org/10.3390/cancers18040555 - 9 Feb 2026
Viewed by 725
Abstract
Background and aims: Liver transplantation is effective against hepatocellular carcinoma (HCC), but recurrence remains a challenge. Traditional criteria based on tumor size, nodule number, and AFP levels have had limited success in predicting aggressiveness. [18F]FDG PET/CT has shown promise in identifying high-risk tumor [...] Read more.
Background and aims: Liver transplantation is effective against hepatocellular carcinoma (HCC), but recurrence remains a challenge. Traditional criteria based on tumor size, nodule number, and AFP levels have had limited success in predicting aggressiveness. [18F]FDG PET/CT has shown promise in identifying high-risk tumor features, including microvascular invasion (MVI), which is a key predictor of recurrence. Methods: In this retrospective, single-center study, all consecutive patients who underwent LT for HCC between 2010 and 2019 were included. Prior to listing, the patients underwent [18F]FDG PET/CT, and explant pathology was analyzed for MVI and other histological features. The primary objective was to identify the predictors of early HCC recurrence (within 24 months after LT). Secondary objectives included identifying predictors of high-risk histological features of the explant, describing recurrence patterns, and assessing post-recurrence survival. Results: The study included 143 patients (median age 59 years [IQR 54–64], 85% males, median MELD 10 [IQR 8–14], median AFP value 8.5 [IQR 4–39] ng/mL) and 40 (28%) with intra-hepatic [18F]FDG PET/CT positivity. HCC recurred post-LT in 25 patients (17%) (median post-LT follow-up 49 months [IQR 28.5–77]) and within 24 months in 12 patients (48%). MVI at the explant stage was independently associated with early recurrence (HR: 7.20, 95% CI 1.82–28.45, p = 0.005), while intra-hepatic [18F]FDG PET/CT positivity before LT independently predicted MVI in explants (OR 3.90, 95% CI 1.30–11.71, p = 0.01). Conclusions: [18F]FDG PET/CT may offer a valuable tool for pre-transplant risk assessment by identifying MVI, which is an independent predictor of early cancer recurrence. Its incorporation into the selection criteria for LT may enhance patient stratification and post-transplant outcomes. Full article
(This article belongs to the Special Issue Surgical and Non-Surgical Convergence in Hepatocellular Carcinoma)
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