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Liver Cancer: Improving Standard Diagnosis and Therapy

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

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 21857

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Dr. Ryota Masuzaki

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Guest Editor

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan
Interests: hepatocellular carcinoma; liver diseases; liver transplantation; gastroenterology
Special Issues, Collections and Topics in MDPI journals

Dr. Tatsuo Kanda

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Guest Editor

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan
Interests: viral hepatitis; hepatocellular carcinoma; innate immunity; unfolded protein response
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liver cancer is a common malignancy worldwide, responsible for 5% of all newly diagnosed cancers. Primary liver cancer ranked sixth for cancer incidence and third for deaths in 2020 globally. There have been significant advances in both the curative and palliative treatment of hepatocellular carcinoma (HCC), including liver resection, local ablation therapy, radiotherapy, systemic chemotherapy, and liver transplantation.

The indication of effective treatment highly depends on the stage of cancer and liver function. The detection of HCC on the early stage primarily depends on imaging studies, such as ultrasonography, computed tomography, and MRI. Sonazoid®, a new contrast agent commercially available since 2007 in Japan, is very useful in detecting liver tumors, including primary liver cancer and metastatic liver cancer because of long-lasting Kupffer phase imaging.

The treatment option is guided based on the Barcelona Clinic Liver Cancer (BCLC) stages. For BCLC A, curative treatments such as radiofrequency ablation, surgical resection, and liver transplantation are indicated. Long-term survival rates of liver cancer patients remain poor, and how to preserve liver function reservoir and how to prevent recurrence of tumor are challenging tasks in the field. For the patients with BCLC B and C, transarterial chemoembolization or systemic chemotherapy is indicated. Newly developed molecular targeted agents (MTA) and immuno-oncology drugs are now available. Several anti-programmed death receptor-1, anti-programmed cell death ligand 1, and anti-cytotoxic lymphocyte antigen 4, are currently being investigated and their combinations with MTA are expected to bring better clinical outcomes. Direct and indirect biomarkers for the prediction and stratification are being vigorously investigated and are expected to be applied in daily clinical practice.

In this Special issue, we focus on recent basic and clinical cancer research into liver cancer.

We welcome broad topics regarding liver cancer through the diagnosis and the treatment from basic to clinical research.

Dr. Ryota Masuzaki
Dr. Tatsuo Kanda
Guest Editors

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Keywords

liver cancer
diagnosis
treatment
basic research
clinical research

Published Papers (12 papers)

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Editorial

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3 pages, 190 KiB

Open AccessEditorial

Liver Cancer: Improving Standard Diagnosis and Therapy

by Ryota Masuzaki

Cancers 2023, 15(18), 4602; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15184602 - 17 Sep 2023

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Abstract

In 2020, liver cancer ranked sixth for incidence (841,000 cases) and fourth for deaths globally (782,000 cases) [...] Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

Research

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12 pages, 755 KiB

Open AccessArticle

Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience

by Friedrich Sinner, Matthias Pinter, Bernhard Scheiner, Thomas Jens Ettrich, Niklas Sturm, Maria A. Gonzalez-Carmona, Oliver Waidmann, Fabian Finkelmeier, Vera Himmelsbach, Enrico N. De Toni, Najib Ben Khaled, Raphael Mohr, Thorben Wilhelm Fründt, Fabian Kütting, Florian van Bömmel, Sabine Lieb, Sebastian Krug, Dominik Bettinger, Michael Schultheiß, Leonie S. Jochheim, Jan Best, Christian Müller, Verena Keitel and Marino Venerito Show full author list Hide full author list

Cancers 2022, 14(23), 5966; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235966 - 02 Dec 2022

Cited by 12 | Viewed by 1898

Abstract

Atezolizumab plus bevacizumab is the standard of care for first-line systemic therapy for advanced hepatocellular carcinoma (aHCC). Data on the efficacy and safety of atezolizumab plus bevacizumab in patients with aHCC who have received prior systemic therapy are not available. Methods: Patients with aHCC who received atezolizumab plus bevacizumab after at least one systemic treatment between December 2018 and March 2022 were retrospectively identified in 13 centers in Germany and Austria. Patient characteristics, tumor response rates, progression-free survival (PFS), overall survival (OS), and adverse events (AE) were analyzed. Results: A total of 50 patients were identified; 41 (82%) were male. The median age at initiation of treatment with atezolizumab plus bevacizumab was 65 years, 41 (82%) patients had cirrhosis, 30 (73%) Child A, 9 (22%) B, and 2 (5%) C. A total of 34 patients (68%) received atezolizumab plus bevacizumab in the second-line setting and 16 (32%) in later lines. The best radiologic tumor responses were complete remission (2%), partial remission (30%), stable disease (36%), and progressive disease (18%), resulting in an objective response rate of 32% and a disease control rate of 68%. Median OS was 16.0 months (95% confidence interval 5.6–26.4 months), and median PFS was 7.1 months (95% confidence interval 4.4–9.8 months). AE grades 3–4 were observed in seven (14%) and resulted in death in three patients (6%). There were five (10%) bleeding events with a grade ≥ 3, including one (2%) with a fatal outcome. Conclusions: Atezolizumab plus bevacizumab is effective in patients with aHCC who did not have access to this option as first-line therapy. The safety profile was consistent with previous reports. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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15 pages, 7551 KiB

Open AccessArticle

Conventional vs. Drug-Eluting Beads Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma—A Propensity Score Weighted Comparison of Efficacy and Safety

by Lynn Jeanette Savic, Evan Chen, Nariman Nezami, Nikitha Murali, Charlie Alexander Hamm, Clinton Wang, MingDe Lin, Todd Schlachter, Kelvin Hong, Christos Georgiades, Julius Chapiro and Fabian M. Laage Gaupp

Cancers 2022, 14(23), 5847; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235847 - 27 Nov 2022

Cited by 4 | Viewed by 1671

Abstract

This study compared the efficacy and safety of conventional transarterial chemoembolization (cTACE) with drug-eluting beads (DEB)-TACE in patients with unresectable hepatocellular carcinoma (HCC). This retrospective analysis included 370 patients with HCC treated with cTACE (n = 248) or DEB-TACE (n = 122) (January 2000–July 2014). Overall survival (OS) was assessed using uni- and multivariate Cox proportional hazards models and Kaplan-Meier analysis. Additionally, baseline imaging was assessed, and clinical and laboratory toxicities were recorded. Propensity score weighting via a generalized boosted model was applied to account for group heterogeneity. There was no significant difference in OS between cTACE (20 months) and DEB-TACE patients (24.3 months, ratio 1.271, 95% confidence interval 0.876–1.69; p = 0.392). However, in patients with infiltrative disease, cTACE achieved longer OS (25.1 months) compared to DEB-TACE (9.2 months, ratio 0.366, 0.191–0.702; p = 0.003), whereas DEB-TACE proved more effective in nodular disease (39.4 months) than cTACE (18 months, ratio 0.458, 0.308–0681; p = 0.007). Adverse events occurred with similar frequency, except for abdominal pain, which was observed more frequently after DEB-TACE (101/116; 87.1%) than cTACE (119/157; 75.8%; p = 0.02). In conclusion, these findings suggest that tumor morphology and distribution should be used as parameters to inform decisions on the selection of embolic materials for TACE for a more personalized treatment planning in patients with unresectable HCC. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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10 pages, 2208 KiB

Open AccessArticle

Comparison of Surgical Resection and Percutaneous Ultrasonographic Guided Radiofrequency Ablation for Initial Recurrence of Hepatocellular Carcinoma in Early Stage following Curative Treatment

by Hideko Ohama, Atsushi Hiraoka, Fujimasa Tada, Kanako Kato, Yoshiko Fukunishi, Emi Yanagihara, Masaya Kato, Hironobu Saneto, Hirofumi Izumoto, Hidetaro Ueki, Takeaki Yoshino, Shogo Kitahata, Tomoe Kawamura, Taira Kuroda, Yoshifumi Suga, Hideki Miyata, Masashi Hirooka, Masanori Abe, Bunzo Matsuura, Tomoyuki Ninomiya and Yoichi Hiasa Show full author list Hide full author list

Cancers 2022, 14(22), 5524; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225524 - 10 Nov 2022

Cited by 4 | Viewed by 1107

Abstract

Background/Aim: The SURF trial showed that surgical resection (SR) and percutaneous ultrasonographic guided radiofrequency ablation (RFA) had equal therapeutic effects for small hepatocellular carcinoma (HCC). However, consensus regarding which treatment is appropriate for initial recurrent early-stage HCC remains lacking. This study aimed to elucidate therapeutic efficacy differences between SR and RFA for initial recurrent early-stage HCC. Materials/Methods: From 2000 to 2021, 371 patients with recurrent early-stage HCC (≤3 cm, ≤3 nodules) after undergoing initial curative treatment with SR or RFA were enrolled (median age 72 years; males 269; Child–Pugh A:B, n = 328:43; SR:RFA, n = 36:335). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated. Results: Although the median albumin–bilirubin (ALBI) score was better in the SR than the RFA group (−2.90 vs. −2.50, p < 0.01), there were no significant differences between them in regard to RFS (median 28.1 months, 95% CI 23.4–50.0 vs. 22.1 months, 95% CI 19.3–26.2; p = 0.34), OS (78.9 months, 95% CI 49.3—not applicable vs. 71.2 months 95% CI, 61.8–84.7; p = 0.337), or complications (8.3% vs. 9.3%; p = 1.0). In sub-analysis for RFS and OS according to ALBI grade revealed no significant differences between the SR and RFA groups (ALBI 1/2 = 28.2/17.5 vs. 24.0/23.4 months; p = 0.881/0684 and ALBI 1/2 = 78.9/58.9 vs. 115.3/52.6 months, p = 0.651/0.578, respectively). Conclusion: This retrospective study found no significant differences in regard to RFS or OS between patients in the SR and the RFA groups for initial recurrence of early-stage HCC after undergoing curative treatment. These results showing equal therapeutic efficacy of SR and RFA confirm the findings of the SURF trial. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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13 pages, 1351 KiB

Open AccessArticle

Analysis of Infectious Complications after Thermal Ablation of Hepatocellular Carcinoma and the Impact on Long-Term Survival

by Yutong Zhang, Xiaoju Li, Xiaoer Zhang, Tongyi Huang, Huanling Guo, Xiaoyan Xie, Chunyang Zhang and Ming Xu

Cancers 2022, 14(21), 5198; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215198 - 23 Oct 2022

Cited by 2 | Viewed by 1327

Abstract

Purpose: This study aims to complete a detailed record of the clinical characteristics and treatment of HCC patients with post-ablation infection and evaluate the infections on recurrence-free survival (RFS) and overall survival (OS) among patients receiving ultrasound-guided thermal ablation. Methods: 3117 patients with liver tumors receiving thermal ablation from January 2010 to December 2021 were analyzed. A total of 49 patients with infectious complications after thermal ablation were selected as the infection group. A total of 49 patients without postoperative infection were randomly selected among those who underwent ablation within three days before or after the treatment date of the infection group as the control group. The clinical characteristics of both groups were analyzed by an independent sample t-test and chi-square test. A log-rank test was performed to compare the RFS and OS data. A multivariate Cox regression model was employed to identify prognostic factors influencing RFS and OS. Subgroup analyses of mild and severe infections were conducted to explore the infection-related situation further. Results: Between mild and severe infection groups, there were statistically significant differences in the infection position (p = 0.043), positive rate of body fluid culture (p = 0.002), proportion of catheter drainage (p = 0.017), use of advanced antibiotics (p = 0.006), and outcome (p = 0.00). The Kaplan–Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (p = 0.028), and severe infection was significantly associated with overall survival (p = 0.049). The cox model showed that postoperative infection was an independent variable for RFS deterioration (HR = 1.724, 95% CI: 1.038–2.862, p = 0.035). Conclusions: Postoperative infection among patients receiving ultrasound-guided thermal ablation adversely affected tumor progression. In addition, empirical antibiotics and catheterization to reduce pressure inside the lesion should be utilized to minimize symptoms in patients with postoperative infection. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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14 pages, 2045 KiB

Open AccessArticle

Analysis of Lenvatinib’s Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma

by Kei Amioka, Tomokazu Kawaoka, Takahiro Kinami, Shintaro Yamasaki, Masanari Kosaka, Yusuke Johira, Shigeki Yano, Kensuke Naruto, Yuwa Ando, Yasutoshi Fujii, Shinsuke Uchikawa, Atsushi Ono, Masami Yamauchi, Michio Imamura, Yumi Kosaka, Kazuki Ohya, Nami Mori, Shintaro Takaki, Keiji Tsuji, Keiichi Masaki, Yoji Honda, Hirotaka Kouno, Hioshi Kohno, Kei Morio, Takashi Moriya, Noriaki Naeshiro, Michihiro Nonaka, Yasuyuki Aisaka, Takahiro Azakami, Akira Hiramatsu, Hiroshi Aikata and Shiro Oka Show full author list Hide full author list

Cancers 2022, 14(20), 5066; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14205066 - 16 Oct 2022

Cited by 3 | Viewed by 1993

Abstract

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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14 pages, 3197 KiB

Open AccessArticle

Well-Controlled Viremia Predicts the Outcome of Hepatocellular Carcinoma in Chronic Viral Hepatitis Patients Treated with Sorafenib

by Yuan-Hung Kuo, Tzu-Hsin Huang, Jing-Houng Wang, Yen-Yang Chen, Ming-Chao Tsai, Yen-Hao Chen, Sheng-Nan Lu, Tsung-Hui Hu, Chien-Hung Chen and Chao-Hung Hung

Cancers 2022, 14(16), 3971; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163971 - 17 Aug 2022

Cited by 5 | Viewed by 1722

Abstract

Without analyzing the status of viremia, hepatitis C virus-related hepatocellular carcinoma (HCV-HCC) patients are proposed to have better prognosis than hepatitis B virus-related HCC (HBV-HCC) patients using sorafenib. We aimed to elucidate the efficacy of concurrent sorafenib and anti-viral treatment for HCC patients with HBV or HCV infection in real world. Between January 2018 and January 2021, 256 unresectable HCC patients receiving first-line sorafenib were evaluated. High-potency nucleoside analogs were used for HBV control, whereas direct-acting antivirals were administered for HCV eradication. Well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before sorafenib. We recruited 116 (65.2%) HBV-HCC patients and 62 (34.8%) HCV-HCC patients. Using sorafenib, progression-free survival and overall survival (OS) rates between these two groups were not different. Before sorafenib, 56% of HBV-HCC patients and 54.8% of HCV-HCC patients had well-controlled viremia and their OS was superior to those who had uncontrolled viremia (15.5 vs. 11.1 months, p = 0.001). Dividing our patients into four subgroups as well-controlled HCV viremia, well-controlled HBV viremia, uncontrolled HCV viremia, and uncontrolled HBV viremia, their OS rates were distributed with a significantly decreasing trend as 21.9 months, 15.0 months, 14.2 months, and 5.7 months (p = 0.009). Furthermore, well-controlled viremia was associated with mortality in multivariate analysis (Hazard ratio: 0.63, 95% confidence interval: 0.42–0.93, p = 0.022). In real-life, HBV or HCV infection did not contribute to the prognosis of HCC patients receiving sorafenib; however, whether viremia was controlled or not did contribute. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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15 pages, 3682 KiB

Open AccessArticle

Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

by Jorge Gutiérrez Sáenz de Santa María, Borja Herrero de la Parte, Gaizka Gutiérrez-Sánchez, Inmaculada Ruiz Montesinos, Sira Iturrizaga Correcher, Carmen Mar Medina and Ignacio García-Alonso

Cancers 2022, 14(2), 371; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020371 - 12 Jan 2022

Cited by 1 | Viewed by 1905

Abstract

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm², and 49.91 ± 15.38 µm²; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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Open AccessArticle

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma

by Kei Amioka, Tomokazu Kawaoka, Masanari Kosaka, Yusuke Johira, Yuki Shirane, Ryoichi Miura, Serami Murakami, Shigeki Yano, Kensuke Naruto, Yuwa Ando, Yumi Kosaka, Yasutoshi Fujii, Kenichiro Kodama, Shinsuke Uchikawa, Hatsue Fujino, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Wataru Okamoto, Masami Yamauchi, Michio Imamura, Nami Mori, Shintaro Takaki, Keiji Tsuji, Keiichi Masaki, Yoji Honda, Hirotaka Kouno, Hiroshi Kohno, Takashi Moriya, Noriaki Naeshiro, Michihiro Nonaka, Hideyuki Hyogo, Yasuyuki Aisaka, Takahiro Azakami, Akira Hiramatsu and Hiroshi Aikata Show full author list Hide full author list

Cancers 2022, 14(2), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020320 - 10 Jan 2022

Cited by 8 | Viewed by 1739

Abstract

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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9 pages, 538 KiB

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The Incidence of Bacteremia and Risk Factors of Post-Radiofrequency Ablation Fever for Patients with Hepato-Cellular Carcinoma

by Po-Yueh Chen, Tsung-Jung Tsai, Hsin-Yi Yang, Chu-Kuang Chou, Li-Jen Chang, Tsung-Hsien Chen, Ming-Tse Hsu, Chien-Chung Fang, Chang-Chao Su, Yu-Ling Lin, Yu-Min Feng and Chi-Yi Chen

Cancers 2021, 13(21), 5303; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215303 - 22 Oct 2021

Cited by 3 | Viewed by 1665

Abstract

Post-radiofrequency ablation (RFA) fever is a self-limited complication of RFA. The correlation between post-RFA fever and bacteremia and the risk factors associated with post-RFA fever have not been evaluated. Patients with newly diagnosed or recurrent hepatocellular carcinoma who underwent ultrasonography-guided RFA between April 2014 and February 2019 were retrospectively enrolled. Post-RFA fever was defined as any episode of body temperature >38.0 °C after RFA during hospitalization. A total of 272 patients were enrolled, and there were 452 applications of RFA. The frequency of post-RFA fever was 18.4% (83/452), and 65.1% (54/83) of post-RFA fevers occurred on the first day after ablation. Patients with post-RFA fever had a longer hospital stay than those without (9.06 days vs. 5.50 days, p < 0.001). Only four (4.8%) patients with post-RFA fever had bacteremia. The independent factors associated with post-RFA fever were younger age (adjusted odds ratio (OR) = 0.96, 95% CI, 0.94–0.99, p = 0.019), low serum albumin level (adjusted OR = 0.49, 95% CI, 0.25–0.95, p = 0.036), general anesthesia (adjusted OR = 2.06, 95% CI, 1.15–3.69, p = 0.015), tumor size (adjusted OR = 1.52, 95% CI, 1.04–2.02, p = 0.032), and tumor number (adjusted OR = 1.71, 95% CI, 1.20–2.45, p = 0.003). Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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Open AccessReview

Suppressors of Cytokine Signaling and Hepatocellular Carcinoma

by Ryota Masuzaki, Tatsuo Kanda, Reina Sasaki, Naoki Matsumoto, Kazushige Nirei, Masahiro Ogawa, Seth J. Karp, Mitsuhiko Moriyama and Hirofumi Kogure

Cancers 2022, 14(10), 2549; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102549 - 22 May 2022

Cited by 11 | Viewed by 2799

Abstract

Cytokines are secreted soluble glycoproteins that regulate cellular growth, proliferation, and differentiation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling and form a classical negative feedback loop in the signaling pathways. There are eight members of the SOCS family. The SOCS proteins are all comprised of a loosely conserved N-terminal domain, a central Src homology 2 (SH2) domain, and a highly conserved SOCS box at the C-terminus. The role of SOCS proteins has been implicated in the regulation of cytokines and growth factors in liver diseases. The SOCS1 and SOCS3 proteins are involved in immune response and inhibit protective interferon signaling in viral hepatitis. A decreased expression of SOCS3 is associated with advanced stage and poor prognosis of patients with hepatocellular carcinoma (HCC). DNA methylations of SOCS1 and SOCS3 are found in HCC. Precise regulation of liver regeneration is influenced by stimulatory and inhibitory factors after partial hepatectomy (PH), in particular, SOCS2 and SOCS3 are induced at an early time point after PH. Evidence supporting the important role of SOCS signaling during liver regeneration also supports a role of SOCS signaling in HCC. Immuno-oncology drugs are now the first-line therapy for advanced HCC. The SOCS can be potential targets for HCC in terms of cell proliferation, cell differentiation, and immune response. In this literature review, we summarize recent findings of the SOCS family proteins related to HCC and liver diseases. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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Open AccessSystematic Review

Per-Feature Accuracy of Liver Imaging Reporting and Data System Locoregional Treatment Response Algorithm: A Systematic Review and Meta-Analysis

by Yeon Jong Huh, Dong Hwan Kim, Bohyun Kim, Joon-Il Choi and Sung Eun Rha

Cancers 2021, 13(17), 4432; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13174432 - 02 Sep 2021

Cited by 8 | Viewed by 1736

Abstract

We aimed to investigate the accuracy of each imaging feature of LI-RADS treatment response (LR-TR) viable category for diagnosing tumor viability of locoregional therapy (LRT)-treated HCC. Studies evaluating the per feature accuracy of the LR-TR viable category on dynamic contrast-enhanced CT or MRI were identified in databases. A bivariate random-effects model was used to calculate the pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of LR-TR viable features. Ten studies assessing the accuracies of LR-TR viable features (1153 treated observations in 971 patients) were included. The pooled sensitivities and specificities for diagnosing viable HCC were 81% (95% confidence interval [CI], 63–92%) and 95% (95% CI, 88–98%) for nodular, mass-like, or irregular thick tissue (NMLIT) with arterial phase hyperenhancement (APHE), 55% (95% CI, 34–75%) and 96% (95% CI, 94–98%) for NMLIT with washout appearance, and 21% (95% CI, 6–53%) and 98% (95% CI, 92–100%) for NMLIT with enhancement similar to pretreatment, respectively. Of these features, APHE showed the highest pooled DOR (81 [95% CI, 25–261]), followed by washout appearance (32 [95% CI, 13–82]) and enhancement similar to pretreatment (14 [95% CI, 5–39]). In conclusion, APHE provided the highest sensitivity and DOR for diagnosing viable HCC following LRT, while enhancement similar to pretreatment showed suboptimal performance. Full article

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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