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International Journal of Surgery... Jan 2024Intermediate-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence rates and poor survival outcomes after surgery....
Effect of transarterial chemoembolization as postoperative adjuvant therapy for intermediate-stage hepatocellular carcinoma with microvascular invasion: a multicenter cohort study.
BACKGROUND
Intermediate-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence rates and poor survival outcomes after surgery. This study aimed to evaluate the efficacy of postoperative transarterial chemoembolization (TACE) on prognosis of intermediate-stage HCC patients with MVI after curative liver resection (LR).
MATERIALS AND METHODS
Patients who had intermediate-stage HCC with MVI and underwent curative LR between January 2013 and December 2019 at three institutions in China were identified for further analysis. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients treated with and without postoperative TACE by propensity score-matching.
RESULTS
A total of 246 intermediate-stage HCC patients with MVI were enrolled, 137 entered into the LR group and 109 entered into the LR+TACE group. The 1-year, 3-year, and 5-year RFS rates were 42.0, 27.2, and 17.8% in LR+TACE group, and 31.8, 18.2, and 8.7% in LR group. The 1-year, 3-year, and 5-year OS rates were 81.7, 47.2, and 26.1% in the LR+TACE group, and 67.3, 35.6, and 18.5% in the LR group. Compared with LR alone, LR+TACE was associated with significantly better RFS [hazard ratio (HR), 1.443; 95% CI: 1.089-1.914; P =0.009] and OS (HR, 1.438; 95% CI: 1.049-1.972; P =0.023). No difference was observed with RFS and OS in single TACE and multiple TACE in the matched cohort.
CONCLUSION
Postoperative adjuvant TACE could be beneficial for intermediate-stage HCC patients with MVI.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Neoplasm Invasiveness; Prognosis; Hepatectomy; Cohort Studies; Retrospective Studies
PubMed: 37812183
DOI: 10.1097/JS9.0000000000000805 -
World Journal of Gastroenterology May 2024A significant number of patients with hepatocellular carcinoma (HCC) are usually diagnosed in advanced stages, that leads to inability to achieve cure. Palliative... (Review)
Review
A significant number of patients with hepatocellular carcinoma (HCC) are usually diagnosed in advanced stages, that leads to inability to achieve cure. Palliative options are focusing on downstaging a locally advanced disease. It is well-supported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery. Hepatic artery infusion chemotherapy can be a potential downstaging strategy, since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Neoplasm Staging; Infusions, Intra-Arterial; Treatment Outcome; Hepatic Artery; Hepatectomy; Palliative Care
PubMed: 38855157
DOI: 10.3748/wjg.v30.i20.2731 -
Molecular and Cellular Probes Feb 2024Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or... (Review)
Review
Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or distal. iCCA, the second most prevalent hepatobiliary cancer following hepatocellular carcinoma (HCC), constitutes 5-20 % of all liver malignancies, with an increasing incidence. The challenging nature of iCCA, combined with nonspecific symptoms, often leads to late diagnoses, resulting in unfavorable outcomes. The advanced phase of this neoplasm is difficult to treat with dismal results. Early diagnosis could significantly reduce mortality attributed to iCCA but remains an elusive goal. The identification of biomarkers specific to iCCA and their translation into clinical practice could facilitate diagnosis, monitor therapy response, and potentially reveal novel interventions and personalized medicine. In this review, we present the current landscape of biomarkers in each of these contexts. In addition to CA19.9, a widely recognized biomarker for iCCA, others such as A1BG, CYFRA 21-1, FAM19A5, MMP-7, RBAK, SSP411, TuM2-PK, WFA, etc., as well as circulating tumor DNA, RNA, cells, and exosomes, are under investigation. Advancing our knowledge and monitoring of biomarkers may enable us to improve diagnosis, prognostication, and apply treatments dynamically and in a more personalized manner.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Bile Duct Neoplasms; Early Detection of Cancer; Cholangiocarcinoma; Biomarkers; Bile Ducts, Intrahepatic; Antigens, Neoplasm; Keratin-19
PubMed: 38244704
DOI: 10.1016/j.mcp.2024.101951 -
Annals of Hepatology 2024Liquid biopsy, specifically the analysis of circulating tumor DNA (ctDNA), offers a non-invasive approach for hepatocellular carcinoma (HCC) diagnosis and management.... (Review)
Review
Liquid biopsy, specifically the analysis of circulating tumor DNA (ctDNA), offers a non-invasive approach for hepatocellular carcinoma (HCC) diagnosis and management. However, its implementation in the clinical setting is difficult due to challenges such as low ctDNA yield and difficulty in understanding the mutation signals from background noise. This review highlights the crucial role of artificial intelligence (AI) in addressing these limitations and in improving discoveries in the field of liquid biopsy for HCC care. Combining AI with liquid biopsy data can offer a promising future for the discovery of novel biomarkers and an AI-powered clinical decision support system (CDSS) can turn liquid biopsy into an important tool for personalized management of HCC. Despite the current challenges, the integration of AI shows promise to significantly improve patient outcomes and revolutionize the field of oncology.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Precision Medicine; Artificial Intelligence; Biomarkers, Tumor; Liquid Biopsy
PubMed: 37972709
DOI: 10.1016/j.aohep.2023.101176 -
Aging Jul 2023Sorafenib, a small-molecule inhibitor targeting several tyrosine kinase pathways, is the standard treatment for advanced hepatocellular carcinoma (HCC). However, not all...
Sorafenib, a small-molecule inhibitor targeting several tyrosine kinase pathways, is the standard treatment for advanced hepatocellular carcinoma (HCC). However, not all patients with HCC respond well to sorafenib, and 30% of patients develop resistance to sorafenib after short-term treatment. Galectin-1 modulates cell-cell and cell-matrix interactions and plays a crucial role in HCC progression. However, whether Galectin-1 regulates receptor tyrosine kinases by sensitizing HCC to sorafenib remains unclear. Herein, we established a sorafenib-resistant HCC cell line (Huh-7/SR) and determined that Galectin-1 expression was significantly higher in Huh-7/SR cells than in parent cells. Galectin-1 knockdown reduced sorafenib resistance in Huh-7/SR cells, whereas Galectin-1 overexpression in Huh-7 cells increased sorafenib resistance. Galectin-1 regulated ferroptosis by inhibiting excessive lipid peroxidation, protecting sorafenib-resistant HCC cells from sorafenib-mediated ferroptosis. Galectin-1 expression was positively correlated with poor prognostic outcomes for HCC patients. Galectin-1 overexpression promoted the phosphorylation of AXL receptor tyrosine kinase (AXL) and MET proto-oncogene, receptor tyrosine kinase (MET) signaling, which increased sorafenib resistance. MET and AXL were highly expressed in patients with HCC, and AXL expression was positively correlated with Galectin-1 expression. These findings indicate that Galectin-1 regulates sorafenib resistance in HCC cells through AXL and MET signaling. Consequently, Galectin-1 is a promising therapeutic target for reducing sorafenib resistance and sorafenib-mediated ferroptosis in patients with HCC.
Topics: Humans; Carcinoma, Hepatocellular; Cell Line, Tumor; Drug Resistance, Neoplasm; Ferroptosis; Galectin 1; Liver Neoplasms; Receptor Protein-Tyrosine Kinases; Sorafenib
PubMed: 37433225
DOI: 10.18632/aging.204867 -
Journal of Nanobiotechnology Oct 2023Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This...
Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.
Topics: Humans; Liver Neoplasms; Neoplasm, Residual; Cell Line, Tumor; Immunogenic Cell Death; B7-H1 Antigen; Nanoparticles; Immunotherapy; Autophagy; Tumor Microenvironment
PubMed: 37789342
DOI: 10.1186/s12951-023-02067-y -
International Journal of Surgery... Oct 2023The type of liver resection (anatomical resection, AR or non-anatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may...
Anatomical resection improves relapse-free survival in colorectal liver metastases in patients with KRAS/NRAS/BRAF mutations or right-sided colon cancer: a retrospective cohort study.
BACKGROUND
The type of liver resection (anatomical resection, AR or non-anatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may persist because some prognostic factors, associated with aggressive tumor biological behavior, have been overlooked.
OBJECTIVE
Our study aimed to investigate the characteristics of patients who would benefit more from anatomical resection for CRLM.
METHODS
Seven hundred twenty-nine patients who underwent hepatic resection of CRLM were retrospectively collected from June 2012 to May 2019. Treatment effects between AR and NAR were compared in full subgroup analyses. Tumor relapse-free survival (RFS) was evaluated by a stratified log-rank test and summarized with the use of Kaplan-Meier and Cox proportional hazards methods.
RESULTS
Among 729 patients, 235 (32.2%) underwent AR and 494 (67.8%) underwent NAR. We showed favorable trends in RFS for AR compared with NAR in the patients with KRAS/NRAS/BRAF mutation (interaction P <0.001) or right-sidedness (interaction P <0.05). Patients who underwent AR had a markedly improved RFS compared with NAR in the cohorts of RAS/NRAS/BRAF mutation (median RFS 23.2 vs. 11.1 months, P <0.001) or right-sidedness (median RFS 31.6 vs. 11.5 months, P <0.001); upon the multivariable analyses, AR [gene mutation: hazard ratio (HR)=0.506, 95% CI=0.371-0.690, P <0.001; right-sidedness: HR=0.426, 95% CI=0.261-0.695, P =0.001) remained prognostic independently. In contrast, patients who underwent AR had a similar RFS compared with those who underwent NAR, in the cohorts of patients with gene wild-type tumors (median RFS 20.5 vs. 21.6 months, P =0.333). or left-sidedness (median RFS 15.8 vs. 19.5 months, P =0.294).
CONCLUSIONS
CRLM patients with gene mutation or right-sidedness can benefit more from AR rather than from NAR.
Topics: Humans; Retrospective Studies; Colorectal Neoplasms; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Disease-Free Survival; Neoplasm Recurrence, Local; Liver Neoplasms; Hepatectomy; Prognosis; Colonic Neoplasms; Mutation; Membrane Proteins
PubMed: 37526097
DOI: 10.1097/JS9.0000000000000562 -
BMC Cancer Dec 2023Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic...
Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients.
BACKGROUND
Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP).
METHODS
Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP's prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging.
RESULTS
Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages.
CONCLUSION
The PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.
Topics: Humans; alpha-Fetoproteins; C-Reactive Protein; Carcinoma, Hepatocellular; Cohort Studies; Hepatectomy; Liver Neoplasms; Neoplasm Staging; Prognosis; Retrospective Studies
PubMed: 38053048
DOI: 10.1186/s12885-023-11693-6 -
Molecular Biomedicine May 2024Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver cancer is commonly... (Review)
Review
Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver cancer is commonly diagnosed at a late stage when surgical interventions are no longer feasible. This situation highlights the critical role of systemic treatments, including targeted therapies, in bettering patient outcomes. Despite numerous studies on the mechanisms underlying liver cancer, tyrosine kinase inhibitors (TKIs) are the only widely used clinical inhibitors, represented by sorafenib, whose clinical application is greatly limited by the phenomenon of drug resistance. Here we show an in-depth discussion of the signaling pathways frequently implicated in liver cancer pathogenesis and the inhibitors targeting these pathways under investigation or already in use in the management of advanced liver cancer. We elucidate the oncogenic roles of these pathways in liver cancer especially hepatocellular carcinoma (HCC), as well as the current state of research on inhibitors respectively. Given that TKIs represent the sole class of targeted therapeutics for liver cancer employed in clinical practice, we have particularly focused on TKIs and the mechanisms of the commonly encountered phenomena of its resistance during HCC treatment. This necessitates the imperative development of innovative targeted strategies and the urgency of overcoming the existing limitations. This review endeavors to shed light on the utilization of targeted therapy in advanced liver cancer, with a vision to improve the unsatisfactory prognostic outlook for those patients.
Topics: Humans; Liver Neoplasms; Signal Transduction; Molecular Targeted Therapy; Protein Kinase Inhibitors; Carcinoma, Hepatocellular; Antineoplastic Agents; Drug Resistance, Neoplasm; Animals
PubMed: 38816668
DOI: 10.1186/s43556-024-00184-0 -
Life Sciences Apr 2024Transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma and selected patients with advanced... (Review)
Review
Transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma and selected patients with advanced hepatocellular carcinoma. However, TACE does not achieve a satisfactory objective response rate, and the concept of TACE refractoriness has been proposed to identify patients who do not fully benefit from TACE. Moreover, repeated TACE is necessary to obtain an optimal and sustained anti-tumour response, which may damage the patient's liver function. Therefore, studies have recently been performed to improve the effectiveness of TACE. In this review, we summarise the detailed molecular mechanisms associated with TACE responsiveness and relapse after this treatment to provide more effective targets for adjuvant therapy while helping to improve TACE regimens.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Arteries; Combined Modality Therapy
PubMed: 38428568
DOI: 10.1016/j.lfs.2024.122540