Current and Future Challenges in the Surgical Treatment of Hepatocellular Carcinoma: A Review

Tsoulfas, Georgios; Agorastou, Polyxeni; Tooulias, Andreas; Marakis, Georgios

doi:10.9738/intsurg-d-13-00122.1

Cited by 9 publications

(11 citation statements)

References 59 publications

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“…The incidence of HCC in developed countries is on the rise due to the progress of hepatitis C viral (HCV) infection in the elderly, as well as to alcohol consumption, the prevalence of obesity and the nonalcoholic fatty liver disease related to the metabolic syndrome 2 , 3 . Over the past few decades, the treatment of HCC has undergone significant changes, such as an introduction of liver transplantation, liver resection, systemic therapy and hepatic artery-targeted chemotherapy 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma

Yue

Sun

2018

Cell Death Dis

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Idelalisib, a selective PI3Kδ inhibitor, has been approved by the FDA for chronic lymphocytic leukemia/small lymphocytic lymphoma treatment and for follicular lymphoma treatment when combined with rituximab. However, the mechanisms of effective action of idelalisib in hepatocellular carcinoma (HCC) remain unclear. In the current study, we aimed to investigate how idelalisib inhibits the growth of HCC cells and enhances the effects of other chemotherapeutic drugs. Our results show that idelalisib treatment promotes Bim induction in HCC via the FoxO3a pathway following PI3K/AKT inactivation. Moreover, our results show that Bim is required for idelalisib-mediated apoptosis in HCC. Idelalisib also synergizes with sorafenib or doxorubicin to induce significant apoptosis in HCC, and Bim is also necessary for the induction of apoptosis by cotreatment. Furthermore, a xenograft experiment reveals that the Bim deficiency abolishes apoptosis and antitumor effects of idelalisib in vivo. In summary, our results indicate a key role of Bim in mediating the antitumor effects of idelalisib in HCC. Our results also support the clinical significance of the drug.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma

Yue

Sun

2018

Cell Death Dis

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“…As of yet, there is no definitive curative treatment strategy for HCC although liver transplantation and hepatic resection, the two main surgical approaches, are potentially curative [18][19]. However, the risk of tumor recurrence still remains a major challenge [20].…”

Section: Surgical Treatment Optionsmentioning

confidence: 99%

A Concise Review on Current Trends in Imaging and Surgical Management of Hepatocellular Carcinoma

Asemota¹,

Saleh²,

Igbinovia³

et al. 2020

Cureus

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Hepatocellular carcinoma (HCC) is a primary cancer of the liver whose incidence has seen an upsurge in the United States within the last 2 decades. Despite improvements in detection and management techniques, the prognosis for patients with HCC generally remains poor. There are multiple factors that have been implicated in the etiology of HCC with cirrhosis occurring as a common final pathway. This review presents a concise summary of current trends in imaging and surgical management of HCC. An internet-based (PubMed) search using the search terms "hepatocellular carcinoma" and "imaging" and "surgical management" was performed. Our search was limited to articles related to human studies published in English during the period of 07/01/2011 to 06/30/2016. A review of all relevant articles was conducted, and findings were summarized. Modern imaging modalities employed in the diagnosis of HCC include ultrasound scan (USS), computed tomography (CT), and magnetic resonance imaging (MRI) scan. The utility of diagnostic imaging is enhanced when interpreted in conjunction with appropriate laboratory tests such as alpha-fetoprotein. The definitive treatment for HCC remains challenging; hepatic resection (HR) and liver transplantation (LT) are two approaches offering potentially curative options. For patients undergoing HR, important considerations include achieving maximum resection while maintaining optimal post-resection liver remnant volume (LRV) and functional capacity (FC), which can be assessed using 3-dimensional CT and indocyanine green clearance. Generally, an LRV of 40-50% is considered an acceptable lower limit for individuals with HCC compared to 20-30% among individuals with normal livers. With increasing knowledge of disease pathology, appropriate patient selection, coupled with advances in anesthesia and surgical technique, overall 5-year survival rates have significantly improved. Challenges associated with LT on the other hand include donor-liver shortages with resultant long wait times and continued disease progression. The scarcity of cadaveric-donor livers has led to employing living-donor livers. Ethical considerations with respect to subjecting potentially healthy donors to undue morbidity and mortality risk however remain. Additional donor-shortage circumventing strategies include employing marginal, domino, and split-organ liver transplants. For patients awaiting transplant, employing bridging therapy such as radiofrequency ablation and transhepatic artery chemoembolization might occasionally help slow disease progression and maintain transplant eligibility. Appropriate patient selection achieved through the Milan and UCSF criteria designed to guide allotment of donor livers to patients with the best chances of survival could help improve outcomes and 5-year survival rates. The main radiological options for diagnosis include USS, CT, and MRI. HR and LT are two distinct surgical options, which in practice can be used to complement one another. 1, 2, 3 3 4 5

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“… 1 Women aged 50 or older are at high risk of suffering from HCC. 2 Early-stage HCC is eligible for hepatectomy, which can improve liver function and the patients’ quality of life, but is also limited to Barcelona Clinic Liver Cancer (BCLC) A stage. 3 Due to the lack of representative early symptoms and effective early-stage diagnostic methods, most patients present advanced liver cancer at first diagnosis and are ineligible for hepatectomy.…”

Section: Introductionmentioning

confidence: 99%

Apatinib-loaded lipid nanobubbles combined with ultrasound-targeted nanobubble destruction for synergistic treatment of HepG2 cells in vitro

Tian

Liu

Zhang

et al. 2018

OTT

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PurposeApatinib, an oral small-molecule antiangiogenetic medicine, is used to treat patients with advanced hepatocellular carcinoma. However, its systemic toxic side effects cannot be ignored. The ultrasound (US)-targeted nanobubble destruction technology can minimize systemic drug exposure and maximize therapeutic efficacy. The aim of this study was to develop novel GPC3-targeted and drug-loaded nanobubbles (NBs) and further assess the associated therapeutic effects on hepatocellular carcinoma cells in vitro.Materials and methodsApatinib-loaded NBs were prepared by a mechanical vibration method. GPC3, a liver tumor homing peptide, was coated onto the surface of apatinib-loaded NBs through biotin–avidin interactions to target liver cancer HepG2 cells. The effects of different treatment groups on cell proliferation, cell cycle, and apoptosis of HepG2 cells were tested.ResultsThe NBs could achieve 68% of optimal drug encapsulation. In addition, ligand binding assays demonstrated that attachment of targeted NBs to human HepG2 liver cancer cells was highly efficient. Furthermore, cell proliferation assays indicated that the antiproliferative activities of GPC3-targeted and apatinib-loaded NBs in combination with US (1 MHz, 1 W/cm2, 30 s) were, respectively, 44.11%±2.84%, 57.09%±6.38%, and 67.51%±2.89% after 24, 48, and 72 h of treatment. Treatment with GPC3-targeted and apatinib-loaded NBs also resulted in a higher proportion of cells in the G1 phase compared with other treatment groups such as apatinib only and nontargeted apatinib-loaded NBs when US was utilized.ConclusionUS-targeted and drug-loaded nanobubble destruction successfully achieved selective growth inhibition and apoptosis in HepG2 cells in vitro. Therefore, GPC3-targeted and apatinib-loaded NBs can be considered a novel chemotherapeutic approach for treating liver cancer in combination with US.

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Current and Future Challenges in the Surgical Treatment of Hepatocellular Carcinoma: A Review

Cited by 9 publications

References 59 publications

RETRACTED ARTICLE: Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma

RETRACTED ARTICLE: Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma

A Concise Review on Current Trends in Imaging and Surgical Management of Hepatocellular Carcinoma

Apatinib-loaded lipid nanobubbles combined with ultrasound-targeted nanobubble destruction for synergistic treatment of HepG2 cells in vitro

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