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Cancers
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Advanced Strategies in the Care of Hepatocellular Carcinoma Patients
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Advanced Strategies in the Care of Hepatocellular Carcinoma Patients

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Survivorship and Quality of Life".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 12449

Special Issue Editors

Prof. Dr. Matteo Donadon

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Guest Editor
Department of Surgery, University Maggiore Hospital, Corso Mazzini 18, 28100 Novara, Italy
Interests: cholangiocarcinoma; Klatskin tumor; colorectal liver metastases; neuroendocrine tumors; hepatocellular carcinoma; hepatic resection; hepatectomy; liver resection; liver surgery; parenchymal-sparing liver surgery; intraoperative ultrasound; liver-specific magnetic resonance imaging; trans-arterial therapy; liver function; FibroScan; pancreatic tumor; pancreatic resection; laparoscopic surgery; robotic surgery
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Guido Torzilli

E-Mail Website
Guest Editor
Director of Department of Surgery, Division of Hepatobiliary Surgery & General Surgery, Humanitas Research Hospital, 20089 Rozzano, Italy
Interests: liver; laparoscopic surgery; intraoperative US of liver
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are honored to be the Guest Editors of this Special Issue of Cancers that summarizes current research in the diagnosis and treatment of hepatocellular carcinoma (HCC). HCC is the most common primary liver cancer, with geographical variations among its prevalence. With HCC still being the leading cause of death in patients with cirrhosis, and considering the worldwide increasing incidence in patients with underlying metabolic associated liver disease, working on HCC should be one of the research priorities. In this Special Issue, we welcome papers that enhance our knowledge of innovative diagnostic and prognostic methods and discuss the results of therapeutic experimentation, including those focused on translational research.

We look forward to receiving your contributions.

Prof. Dr. Matteo Donadon
Prof. Dr. Guido Torzilli 
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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
  • hepatic resection
  • hepatectomy
  • liver resection
  • liver surgery
  • parenchymal-sparing liver surgery
  • intraoperative ultrasound
  • liver-specific magnetic resonance imaging
  • trans-arterial therapy
  • liver function
  • FibroScan

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Published Papers (7 papers)

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Research

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16 pages, 1758 KiB  
Article
Predictive Risk Factors and Scoring Systems Associated with the Development of Hepatocellular Carcinoma in Chronic Hepatitis B
by Ploutarchos Pastras, Evaggelos Zazas, Maria Kalafateli, Ioanna Aggeletopoulou, Efthymios P. Tsounis, Stavros Kanaloupitis, Konstantinos Zisimopoulos, Eirini-Eleni-Konstantina Kottaridou, Aspasia Antonopoulou, Dimosthenis Drakopoulos, Georgia Diamantopoulou, Aggeliki Tsintoni, Konstantinos Thomopoulos and Christos Triantos
Cancers 2024, 16(14), 2521; https://doi.org/10.3390/cancers16142521 - 12 Jul 2024
Viewed by 707
Abstract
Chronic hepatitis B (CHB) infection constitutes a leading cause of hepatocellular carcinoma (HCC) development. The identification of HCC risk factors and the development of prognostic risk scores are essential for early diagnosis and prognosis. The aim of this observational, retrospective study was to [...] Read more.
Chronic hepatitis B (CHB) infection constitutes a leading cause of hepatocellular carcinoma (HCC) development. The identification of HCC risk factors and the development of prognostic risk scores are essential for early diagnosis and prognosis. The aim of this observational, retrospective study was to evaluate baseline risk factors associated with HCC in CHB. Six hundred thirty-two consecutive adults with CHB (n = 632) [median age: 46 (IQR: 24)], attending the outpatients’ Hepatology clinics between 01/1993–09/2020 were evaluated. Core promoter mutations and cirrhosis-HCC (GAG-HCC), Chinese University-HCC (CU-HCC), risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B), Fibrosis-4 (FIB-4), and Platelet Age Gender–HBV (PAGE-B) prognostic scores were calculated, and receiver operating curves were used to assess their prognostic performance. HCC was developed in 34 (5.38%) patients. In the multivariable Cox regression analysis, advanced age (HR: 1.086, 95% CI: 1.037–1.137), male sex (HR: 7.696, 95% CI: 1.971–30.046), alcohol abuse (HR: 2.903, 95% CI: 1.222–6.987) and cirrhosis (HR: 21.239, 95% CI: 6.001–75.167) at baseline were independently associated with the development of HCC. GAG-HCC and PAGE-B showed the highest performance with c-statistics of 0.895 (95% CI: 0.829–0.961) and 0.857 (95% CI: 0.791–0.924), respectively. In the subgroup of patients with cirrhosis, the performance of all scores declined. When treated and untreated patients were studied separately, the discriminatory ability of the scores differed. In conclusion, HCC development was independently associated with advanced age, male sex, alcohol abuse, and baseline cirrhosis among a diverse population with CHB. GAG-HCC and PAGE-B showed high discriminatory performance to assess the risk of HCC development in these patients, but these performances declined in the subgroup of patients with cirrhosis. Further research to develop scores more specific to certain CHB subgroups is needed. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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12 pages, 1279 KiB  
Article
Real-World Treatment Patterns, Clinical Outcomes, Healthcare Resource Utilization, and Costs in Advanced Hepatocellular Carcinoma in Ontario, Canada
by Soo Jin Seung, Hasnain Saherawala, YongJin Kim, Jimmy Tieu, Sharon Wang, Cal Shephard and Dominick Bossé
Cancers 2024, 16(12), 2232; https://doi.org/10.3390/cancers16122232 - 15 Jun 2024
Viewed by 869
Abstract
The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study [...] Read more.
The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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10 pages, 642 KiB  
Article
Alpha-Fetoprotein Response after First Transarterial Chemoembolization (TACE) and Complete Pathologic Response in Patients with Hepatocellular Cancer
by Łukasz Masior, Maciej Krasnodębski, Mikołaj Kuncewicz, Kacper Karaban, Igor Jaszczyszyn, Emilia Kruk, Milena Małecka-Giełdowska, Krzysztof Korzeniowski, Wojciech Figiel, Marek Krawczyk, Tadeusz Wróblewski and Michał Grąt
Cancers 2023, 15(15), 3962; https://doi.org/10.3390/cancers15153962 - 4 Aug 2023
Viewed by 1662
Abstract
Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change [...] Read more.
Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively (p = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively (p = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, p = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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11 pages, 591 KiB  
Article
Impact of Oocyte Extract Supplement on Quality of Life after Hepatectomy for Liver Tumours: A Prospective, Multicentre, Double-Blind Randomized Clinical Trial
by Matteo Donadon, Angela Palmisano, Mariano Bizzarri, Roberto Ceriani, Luigi Veneroni, Gabriele Donati, Davide Tassinari, Massimo Giuseppe Viola, Emiliano Tamburini and Guido Torzilli
Cancers 2023, 15(10), 2809; https://doi.org/10.3390/cancers15102809 - 18 May 2023
Viewed by 2059
Abstract
Background: Previous studies on oocyte extract supplementation showed benefits in patients with liver tumours. In this trial, we hypothesized that the oocyte extract supplement impacted the QoL after hepatectomy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Methods: This was a multicentre, double-blind, randomized clinical [...] Read more.
Background: Previous studies on oocyte extract supplementation showed benefits in patients with liver tumours. In this trial, we hypothesized that the oocyte extract supplement impacted the QoL after hepatectomy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Methods: This was a multicentre, double-blind, randomized clinical trial designed to assess the QoL of patients receiving a supplement of oocyte extract or placebo postoperatively. QoL was assessed using the Short Form-36 questionnaire in participants randomly assigned to treatment (Synchrolevels) or placebo. All study personnel and participants were masked to treatment assignment. The endpoint was the change in the QoL score. Results: Between June 2018 and September 2022, 66 of 128 expected patients were considered as per interim analysis, of which 33 were assigned to the treatment and 33 to the placebo group. Baseline and clinicopathological characteristics were similar between the two groups. In the treatment group, the health, mental and psychological status improved for many of the items considered, reaching statistical significance, while in the placebo group, those items either did not change or were impaired in comparison with the corresponding baseline. Conclusions: Supplementation with oocyte extract modifies QoL after liver surgery by enhancing functional recovery. Further in-depth studies are required to confirm this evidence. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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Review

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19 pages, 1194 KiB  
Review
Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review
by Elena Panettieri, Andrea Campisi, Agostino M. De Rose, Caterina Mele, Felice Giuliante, Jean-Nicolas Vauthey and Francesco Ardito
Cancers 2024, 16(12), 2183; https://doi.org/10.3390/cancers16122183 - 10 Jun 2024
Viewed by 1186
Abstract
In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular [...] Read more.
In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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32 pages, 3336 KiB  
Review
Incidental Findings in Pediatric Patients: How to Manage Liver Incidentaloma in Pediatric Patients
by Andrius Cekuolis, Dagmar Schreiber-Dietrich, Rasa Augustinienė, Heike Taut, Judy Squires, Edda L. Chaves, Yi Dong and Christoph F. Dietrich
Cancers 2023, 15(8), 2360; https://doi.org/10.3390/cancers15082360 - 18 Apr 2023
Cited by 4 | Viewed by 2598
Abstract
The World Federation for Ultrasound in Medicine and Biology (WFUMB) is addressing the issue of incidental findings (IFs) with a series of publications entitled “Incidental imaging findings—the role of ultrasound”. IFs in the liver of newborns and children are rare and much less [...] Read more.
The World Federation for Ultrasound in Medicine and Biology (WFUMB) is addressing the issue of incidental findings (IFs) with a series of publications entitled “Incidental imaging findings—the role of ultrasound”. IFs in the liver of newborns and children are rare and much less commonly encountered than in adults; as a result, they are relatively much more frequently malignant and life-threatening, even when they are of benign histology. Conventional B-mode ultrasound is the well-established first line imaging modality for the assessment of liver pathology in pediatric patients. US technological advances, resulting in image quality improvement, contrast-enhanced ultrasound (CEUS), liver elastography and quantification tools for steatosis have expanded the use of ultrasound technology in daily practice. The following overview is intended to illustrate incidentally detected liver pathology covering all pediatric ages. It aims to aid the examiner in establishing the final diagnosis. Management of incidentally detected focal liver lesions (FLL) needs to take into account the diagnostic accuracy of each imaging modality, the patient’s safety issues (including ionizing radiation and nephrotoxic contrast agents), the delay in diagnosis, the psychological burden on the patient and the cost for the healthcare system. Moreover, this paper should help the pediatric clinician and ultrasound practitioner to decide which pathologies need no further investigation, which ones require interval imaging and which cases require further and immediate diagnostic procedures. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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16 pages, 990 KiB  
Review
Surgical Strategies for Recurrent Hepatocellular Carcinoma after Resection: A Review of Current Evidence
by Flavio Milana, Michela Anna Polidoro, Simone Famularo, Ana Lleo, Renzo Boldorini, Matteo Donadon and Guido Torzilli
Cancers 2023, 15(2), 508; https://doi.org/10.3390/cancers15020508 - 13 Jan 2023
Cited by 5 | Viewed by 2508
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking. In these cases, surgery still represents a curative option with both redo hepatectomy and/or salvage liver transplantation, which are considered valid treatments in selected patients. In the current era of personalised medicine with promises of new systemic-targeted immuno-chemotherapies, we wished to perform a narrative review of the literature on the role of surgical strategies for rHCC. Full article
(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)
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