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13 pages, 3943 KiB

Open AccessArticle

Textbook Outcome of Laparoscopic Microwave Ablation for Hepatocellular Carcinoma

by Jacopo Lanari, Silvia Caregari, Ilaria Billato, Enrico Gringeri, Francesco D’Amico, Giancarlo Gemo, Domenico Bassi, Francesco Enrico D’Amico, Riccardo Boetto, Alessandra Bertacco, Andrea Marchini, Sara Lazzari, Marco Brolese, Mattia Ballo, Alessandro Vitale and Umberto Cillo

Cancers 2023, 15(2), 436; https://doi.org/10.3390/cancers15020436 - 10 Jan 2023

Cited by 4 | Viewed by 2102

Abstract

In the context of spreading interest in textbook outcome (TO) evaluation in different fields, we aimed to investigate an uncharted procedure, that is, laparoscopic microwave ablation (MWA) for hepatocellular carcinoma (HCC). Absence of post-MWA complications, a hospital stay of three days, no mortality [...] Read more.

In the context of spreading interest in textbook outcome (TO) evaluation in different fields, we aimed to investigate an uncharted procedure, that is, laparoscopic microwave ablation (MWA) for hepatocellular carcinoma (HCC). Absence of post-MWA complications, a hospital stay of three days, no mortality nor readmission within 30 days, and complete response of the target lesion at post-MWA CT scan defined TO achievement. Patients treated between January 2014 and March 2021 were retrospectively reviewed, and of the 521 patients eligible for the study, 337 (64.7%) fulfilled all the quality indicators to achieve the TO. The absence of complications was the main limiting factor for accomplishing TO. At multivariable analysis, Child–Pugh B cirrhosis, age of more than 70 years old, three nodules, and MELD score ≥ 15 were associated with decreased probabilities of TO achievement. A score based on these factors was derived from multivariable analysis, and patients were divided into three risk groups for TO achievement. At survival analysis, overall survival (OS) was significantly (p = 0.001) higher in patients who achieved TO than those who did not. Moreover, OS evaluation in the three risk groups showed a trend coherent with TO achievement probability. The present study, having assessed the first TO for laparoscopic MWA for HCC, encourages further broader consensus on its definition and, on its basis, on the development of clinically relevant tools for managing treatment allocation. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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14 pages, 895 KiB

Open AccessArticle

Prolonged Survival after Recurrence in HCC Resected Patients Using Repeated Curative Therapies: Never Give Up!

by Cyprien Toubert, Boris Guiu, Bader Al Taweel, Eric Assenat, Fabrizio Panaro, François-Regis Souche, Jose Ursic-Bedoya, Francis Navarro and Astrid Herrero

Cancers 2023, 15(1), 232; https://doi.org/10.3390/cancers15010232 - 30 Dec 2022

Cited by 6 | Viewed by 2597

Abstract

Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate [...] Read more.

Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child–Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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13 pages, 2155 KiB

Open AccessArticle

The Clinical Impact of Hepatic Arterial Infusion Chemotherapy New-FP for Hepatocellular Carcinoma with Preserved Liver Function

by Hideki Iwamoto, Takashi Niizeki, Hiroaki Nagamatsu, Kazuomi Ueshima, Joji Tani, Teiji Kuzuya, Kazuhiro Kasai, Youhei Kooka, Atsushi Hiraoka, Rie Sugimoto, Takehiro Yonezawa, Satoshi Tanaka, Akihiro Deguchi, Shigeo Shimose, Tomotake Shirono, Miwa Sakai, Hiroyuki Suzuki, Etsuko Moriyama, Hironori Koga, Takuji Torimura, Takumi Kawaguchi, New FP Study Group and Kurume Liver Cancer Study Group of Japan Show full author list Hide full author list

Cancers 2022, 14(19), 4873; https://doi.org/10.3390/cancers14194873 - 5 Oct 2022

Cited by 7 | Viewed by 2496

Abstract

Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy [...] Read more.

Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy (HAIC) regimens New-FP and sorafenib for various tumor conditions in preserved liver function. Methods: We retrospectively collected the data of 1709 patients with HCC who were treated with New-FP or sorafenib. Survival was assessed after propensity score matching. Subgroup analyses were conducted: cohort 1 (no MVI or extrahepatic spread (EHS)), cohort 2 (MVI only), cohort 3 (EHS only), cohort 4 (MVI and EHS), and cohort 5 (major PVTT). Results: The New-FP group had a longer median survival time (MST) than the sorafenib in the whole analysis (18 vs. 9 months; p < 0.0001). New-FP demonstrated a longer MST compared with sorafenib in cohort 2 and cohort 4. In cohort 5, the MST of the New-FP group was 16 months, while that of sorafenib was 6 months (p < 0.0001). For major PVTT-HCC, the response rate of New-FP was 73.0%. The MST of patients who achieved complete response with New-FP was 59 months. Conclusions: HAIC using New-FP is promising for patients with MVI- and major PVTT-HCC in preserved liver function. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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19 pages, 3466 KiB

Open AccessArticle

by Junling Wu, Zeman Lin, Daihan Ji, Zhenli Li, Huarong Zhang, Shuting Lu, Shenglin Wang, Xiaolong Liu and Lu Ao

Cancers 2022, 14(16), 3957; https://doi.org/10.3390/cancers14163957 - 16 Aug 2022

Cited by 2 | Viewed by 2157

Abstract

Recurrence is the main factor affecting the prognosis of early hepatocellular carcinoma (HCC), which is not accurately evaluated by clinical indicators. The metabolic heterogeneity of HCC hints at the possibility of constructing a stratification model to predict the clinical outcome. On the basis [...] Read more.

Recurrence is the main factor affecting the prognosis of early hepatocellular carcinoma (HCC), which is not accurately evaluated by clinical indicators. The metabolic heterogeneity of HCC hints at the possibility of constructing a stratification model to predict the clinical outcome. On the basis of the relative expression orderings of 2939 metabolism-related genes, an individualized signature with 10 metabolism-related gene pairs (10-GPS) was developed from 250 early HCC samples in the discovery datasets, which stratified HCC patients into the high- and low-risk subgroups with significantly different survival rates. The 10-GPS was validated in 311 public transcriptomic samples from two independent validation datasets. A nomogram that included the 10-GPS, age, gender, and stage was constructed for eventual clinical evaluation. The low-risk group was characterized by lower proliferation, higher metabolism, increased activated immune microenvironment, and lower TIDE scores, suggesting a better response to immunotherapy. The high-risk group displayed hypomethylation, higher copy number alterations, mutations, and more overexpression of immune-checkpoint genes, which might jointly lead to poor outcomes. The prognostic accuracy of the 10-GPS was further validated in 47 institutional transcriptomic samples and 101 public proteomic samples. In conclusion, the 10-GPS is a robust predictor of the clinical outcome for early HCC patients and could help evaluate prognosis and characterize molecular heterogeneity. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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21 pages, 7420 KiB

Open AccessArticle

Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma

by Sonia Simón Serrano, Michele Tavecchio, Alvar Grönberg, Wondossen Sime, Mohamed Jemaà, Steven Moss, Matthew Alan Gregory, Philippe Gallay, Eskil Elmér, Magnus Joakim Hansson and Ramin Massoumi

Cancers 2021, 13(12), 3041; https://doi.org/10.3390/cancers13123041 - 18 Jun 2021

Cited by 8 | Viewed by 4189

Abstract

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient’s life expectancy by [...] Read more.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient’s life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G₂/M phase of the cell cycle. NV651 reduced tumor growth in vivo using an HCC xenograft model without affecting the body weights of the animals. The safety aspects of NV651 were also confirmed in primary human hepatocytes without any cytotoxic effects. Based on the results obtained in this study, we propose NV651 as a potential treatment strategy for HCC. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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14 pages, 1861 KiB

Open AccessArticle

Liver Transplantation for T2 Hepatocellular Carcinoma during the COVID-19 Pandemic: A Novel Model Balancing Individual Benefit against Healthcare Resources

by Umberto Cillo, Alessandro Vitale, Michael L. Volk, Anna Chiara Frigo, Paolo Feltracco, Annamaria Cattelan, Giuseppina Brancaccio, Giuseppe Feltrin, Paolo Angeli, Patrizia Burra, Sara Lonardi, Silvia Trapani and Massimo Cardillo

Cancers 2021, 13(6), 1416; https://doi.org/10.3390/cancers13061416 - 19 Mar 2021

Cited by 8 | Viewed by 2587

Abstract

The COVID-19 pandemic caused temporary drops in the supply of organs for transplantation, leading to renewed debate about whether T2 hepatocellular carcinoma (HCC) patients should receive priority during these times. The aim of this study was to provide a quantitative model to aid [...] Read more.

The COVID-19 pandemic caused temporary drops in the supply of organs for transplantation, leading to renewed debate about whether T2 hepatocellular carcinoma (HCC) patients should receive priority during these times. The aim of this study was to provide a quantitative model to aid decision-making in liver transplantation for T2 HCC. We proposed a novel ethical framework where the individual transplant benefit for a T2 HCC patient should outweigh the harm to others on the waiting list, determining a “net benefit”, to define appropriate organ allocation. This ethical framework was then translated into a quantitative Markov model including Italian averages for waiting list characteristics, donor resources, mortality, and transplant rates obtained from a national prospective database (n = 8567 patients). The net benefit of transplantation in a T2 HCC patient in a usual situation varied from 0 life months with a model for end-stage liver disease (MELD) score of 15, to 34 life months with a MELD score of 40, while it progressively decreased with acute organ shortage during a pandemic (i.e., with a 50% decrease in organs, the net benefit varied from 0 life months with MELD 30, to 12 life months with MELD 40). Our study supports the continuation of transplantation for T2 HCC patients during crises such as COVID-19; however, the focus needs to be on those T2 HCC patients with the highest net survival benefit. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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14 pages, 1103 KiB

Open AccessArticle

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection

by Hannah Miller, Zoltan Czigany, Isabella Lurje, Sophie Reichelt, Jan Bednarsch, Pavel Strnad, Christian Trautwein, Christoph Roderburg, Frank Tacke, Nadine Therese Gaisa, Ruth Knüchel-Clarke, Ulf Peter Neumann and Georg Lurje

Cancers 2020, 12(12), 3826; https://doi.org/10.3390/cancers12123826 - 18 Dec 2020

Cited by 12 | Viewed by 2844

Abstract

Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact [...] Read more.

Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)–restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of “high-expression” variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients’ individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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Review

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11 pages, 12046 KiB

Open AccessReview

Contrast-Enhanced Ultrasound for Monitoring Treatment Response in Different Stages of Hepatocellular Carcinoma

by Mariella Faccia, Matteo Garcovich, Maria Elena Ainora, Laura Riccardi, Maurizio Pompili, Antonio Gasbarrini and Maria Assunta Zocco

Cancers 2022, 14(3), 481; https://doi.org/10.3390/cancers14030481 - 18 Jan 2022

Cited by 27 | Viewed by 3281

Abstract

The capacity of contrast-enhanced ultrasound (CEUS) to detect microvessel perfusion has received much attention in cancer imaging since it can be used to evaluate the enhancement patterns of the lesions during all vascular phases in real time, with higher temporal resolution as compared [...] Read more.

The capacity of contrast-enhanced ultrasound (CEUS) to detect microvessel perfusion has received much attention in cancer imaging since it can be used to evaluate the enhancement patterns of the lesions during all vascular phases in real time, with higher temporal resolution as compared other imaging modalities. A rich body of literature has demonstrated the potential usefulness of CEUS in the assessment of HCC in response to both locoregional and systemic therapies. It is useful to evaluate the efficacy of ablation immediately after treatment to provide guidance for the retreatment of residual unablated tumors. In patients treated with transarterial chemoembolization (TACE), CEUS showed a high degree of concordance with computed tomography and magnetic resonance for the differentiation of responders from non-responders. Dynamic CEUS (D-CEUS) has emerged as a promising tool for the depicting changes in tumor perfusion during anti-angiogenetic treatment that can be associated with tumor response and clinical outcome. This article provides a general review of the current literature regarding the usefulness of CEUS in monitoring HCC response to therapy, highlighting the role of the procedure in different stages of the disease. Full article

(This article belongs to the Special Issue Curative Strategies for the Management of Hepatocellular Cancer)

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