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INTRODUCTION: Visceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer. METHODS: We identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models. RESULTS: In total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer. CONCLUSION: Patients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer.

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Neoplasias Óseas , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/mortalidad , Anciano , Neoplasias Óseas/secundario , Neoplasias Óseas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Pronóstico , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Estimación de Kaplan-Meier , Metástasis de la Neoplasia , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales

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BACKGROUND: The prognosis of patients with hepatocellular cancer is substantially correlated with the abnormal expression of growing long non-coding RNA small nucleolar host gene RNA (SNHG) families in liver cancer tissues. This study aimed to examine the relationship between SNHG expression and liver cancer prognosis. METHODS: After searching six internet databases, pertinent manuscripts were found based on inclusion and exclusion criteria. To determine whether SNHG expression levels affect liver cancer prognosis, raw data were collected and hazard ratios (HRs) and odds ratios (ORs) were calculated. The results were examined for potential publication bias using the sensitivity analysis and Beeg's test. RESULTS: Most SNHG family members were up-regulated in liver cancer tissues. High SNHG expression predicts poor liver cancer outcomes of, including overall survival (OS) (HR: 1.697, 95% confidence interval [CI]: 1.373-2.021), especially SNHG5 (the HR of OS is 4.74, 95%CI range from 1.35 to 6.64), progression-free survival (HR: 1.85, 95% CI: 1.25-2.73), tumor, node, metastasis (TNM) stage (OR: 1.696, 95% CI: 1.436-2.005), lymph node metastasis (OR: 2.383, 95% CI: 1.098-5.173), and tumor size (OR: 1363, 95% CI: 1.165-1.595). The OS results were found to be reliable and robust, as indicated by the sensitivity analysis. Additionally, Beeg's test demonstrated the absence of any potential publication bias for each result. CONCLUSION: In liver cancer tissues, most SNHGs are highly expressed, which may signal poor prognosis. SNHG has the potential to be an intriguing predictive marker and a prospective therapeutic target for liver cancer.

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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Nucleolar Pequeño , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Pronóstico , ARN Nucleolar Pequeño/genética , Biomarcadores de Tumor/genética , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica

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BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

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Carcinoma Hepatocelular , Hepatectomía , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Neoplasias Hepáticas , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/etiología , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Pronóstico , Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Nucleósidos/uso terapéutico , Estudios Retrospectivos , Adulto , Anciano , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología

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Inflammation plays a pivotal role in cancer development, with chronic inflammation promoting tumor progression and treatment resistance, whereas acute inflammatory responses contribute to protective anti-tumor immunity. Gasdermin D (GSDMD) mediates the release of pro-inflammatory cytokines such as IL-1ß. While the release of IL-1ß is directly linked to the progression of several types of cancers, the role of GSDMD in cancer is less clear. In this study, we show that GSDMD expression is upregulated in human breast, kidney, liver, and prostate cancer. Higher GSDMD expression correlated with increased survival in primary breast invasive carcinoma (BRCA), but not in liver hepatocellular carcinoma (LIHC). In BRCA, but not in LIHC, high GSDMD expression correlated with a myeloid cell signature associated with improved prognosis. To further investigate the role of GSDMD in anticancer immunity, we induced breast cancer and hepatoma tumors in GSDMD-deficient mice. Contrary to our expectations, GSDMD deficiency had no effect on tumor growth, immune cell infiltration, or cytokine expression in the tumor microenvironment, except for Cxcl10 upregulation in hepatoma tumors. In vitro and in vivo innate immune activation with TLR ligands, that prime inflammatory responses, revealed no significant difference between GSDMD-deficient and wild-type mice. These results suggest that the impact of GSDMD on anticancer immunity is dependent on the tumor type. They underscore the complex role of inflammatory pathways in cancer, emphasizing the need for further exploration into the multifaceted effects of GSDMD in various tumor microenvironments. As several pharmacological modulators of GSDMD are available, this may lead to novel strategies for combination therapy in cancer.

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Neoplasias de la Mama , Péptidos y Proteínas de Señalización Intracelular , Proteínas de Unión a Fosfato , Microambiente Tumoral , Animales , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , Femenino , Humanos , Ratones , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Microambiente Tumoral/inmunología , Ratones Noqueados , Modelos Animales de Enfermedad , Línea Celular Tumoral , Citocinas/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/genética , Gasderminas

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PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. METHODS: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. RESULTS: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03-0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. CONCLUSION: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies.

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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Trasplante de Hígado , Estadificación de Neoplasias , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Humanos , Selección de Paciente , Tasa de Supervivencia

RESUMEN

Background: Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). Methods: From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect. Results: This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, P < 0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, P < 0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS. Conclusion: The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety. Systematic review registration: PROSPERO, identifier (CRD42023420093).

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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada

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BACKGROUND: Primary liver cancer is the third leading cause of cancer deaths worldwide and has one of the worst 5-year survival rates. This study examines US primary liver cancer incidence and incidence-based mortality trends over four decades. RESEARCH DESIGN AND METHODS: The SEER-9 registry was used to study primary liver cancer cases from 1978 to 2018. The incidence and mortality rates were calculated based on gender, age, race, and stage of diagnosis. Joinpoint regression software was used to calculate the annual percent change. RESULTS: The overall incidence rate of primary liver cancer from 1978 to 2018 increased by 2.71%/year (p<0.001). Rates in patients <50 years old began to fall in 2002 at a rate of -3.62%/year (p<0.001). Similarly, the incidence-based mortality rates for primary liver cancer increased by 2.15%/year (p<0.001). Whereas Whites incidence-based mortality rates began to plateau in 2012 (0.18%/year; p = 0.84), Blacks rates have declined since 2010 (-2.93%/year; p = 0.03), and Asian rates have declined since 1999 (-1.30%/year; p<0.001). CONCLUSION: While the overall primary liver cancer incidence and incidence-based mortality have been increasing over the last four decades, there was an observed decline in incidence and incidence-based mortality in recent years, especially among at-risk subgroups.

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Neoplasias Hepáticas , Programa de VERF , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/epidemiología , Masculino , Estados Unidos/epidemiología , Femenino , Incidencia , Persona de Mediana Edad , Anciano , Adulto , Tasa de Supervivencia , Anciano de 80 o más Años , Mortalidad/tendencias

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INTRODUCTION: We assessed chronic liver disease (CLD)-related mortality in the U.S. using death data (2011-2021) obtained from National Vital Statistics System (NVSS). The average annual percentage change (AAPC) from the models selected by Joinpoint regression analysis over the pre-pandemic (2011-2019) and the 2019-2021 were reported because non-linear trend in death rates were observed over the 2011-2021. Liver-specific death was defined as an underlying cause of death and Chronic liver disease (CLD)-related death was defined as any cause of death. During the pre-pandemic, age-standardized HCC- and cirrhosis-specific death rates were annually increased by AAPC = +1.18% (95% confidence interval, 0.34% to 2.03%) and AAPC = +1.95% (1.56% to 2.35%). In contrast, during the 2019-2021, the AAPC in age-standardized cirrhosis-specific death rate (per 100,000) accelerated by up to AAPC +11.25% (15.23 in 2019 to 18.86 in 2021) whereas that in age-standardized HCC-specific death rate slowed to -0.39 (-1.32% to 0.54%) (3.86 in 2019 to 3.84 in 2021). Compared to HCC-specific deaths, cirrhosis-specific deaths were more likely to be non-Hispanic white (72.4% vs. 62.0%) and non-Hispanic American Indian and Alaska native (AIAN) (2.2% vs. 1.1%) and have NAFLD (45.3% vs. 12.5%) and ALD (27.6% vs. 22.0%). During the 2019-2021, the age-standardized HCV- and HBV-related death rate stabilized, whereas the age-standardized NAFLD- and ALD-related deaths rate increased to 20.16 in 2021 (AAPC = +12.13% [7.76% to 16.68%]) and to 14.95 in 2021 (AAPC = +18.30% [13.76% to 23.03%]), which were in contrast to much smaller incremental increases during the pre-pandemic (AAPC = +1.82% [1.29% to 2.35%] and AAPC = +4.54% [3.97% to 5.11%]), respectively). The most pronounced rise in the age-standardized NAFLD-related death rates during the pandemic was observed among AIAN (AAPC = +25.38%), followed by non-Hispanic White female (AAPC = +14.28%), whereas the age-standardized ALD-related death rates during the pandemic were highest among AIAN (AAPC = +40.65%), followed by non-Hispanic Black female (AAPC = +26.79%). CONCLUSIONS: COVID-19 pandemic had a major negative impact on cirrhosis-specific and CLD-related mortality in the U.S. with significant racial and gender disparities.

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COVID-19 , Estadísticas Vitales , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Estados Unidos/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pandemias , Hepatopatías/mortalidad , Hepatopatías/epidemiología , Cirrosis Hepática/mortalidad , Cirrosis Hepática/epidemiología , Enfermedad Crónica/mortalidad , Adulto , Causas de Muerte , SARS-CoV-2/aislamiento & purificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/epidemiología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/epidemiología , Anciano de 80 o más Años

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Liver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges. This study aims to develop novel diagnostic and prognostic models while identifying new biomarkers for improved HCC treatment. Diagnostic and prognostic models for HCC were constructed using traditional binary classification methods and machine learning algorithms based on the TCGA database (Downloaded in August 2023). The mechanisms by which APLN (Apelin) affects HCC were investigated using single-cell sequencing data sourced from the GEO database (GSE149614). The diagnostic models yielded by various algorithms could effectively distinguished HCC samples from normal ones. The prognostic model, composed of four genes, was constructed using LASSO and Cox regression algorithms, demonstrating good performance in predicting the three-year survival rate of HCC patients. The HCC biomarker Apelin (APLN) was identified in this study. APLN in liver cancer tissues mainly comes from endothelial cells and is associated with the carcinogenesis of these cells. APLN expression is significantly upregulated in liver cancer tissues, marking it as a viable indicator of endothelial cell malignancy in HCC. Furthermore, APLN expression was determined to be an independent predictor of tumor endothelial cell carcinogenesis, unaffected by its modifications such as single nucleotide variation, copy number variation, and methylation. Additionally, liver cancers characterized by high APLN expression are likely to progress rapidly after T2 stage. Our study presents diagnostic and prognostic models for HCC with appreciably improved accuracy and reliability compared to previous reports. APLN is a reliable HCC biomarker and contributes to the establishment of our models.

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Apelina , Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Apelina/metabolismo , Apelina/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino

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BACKGROUND: Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. METHODS: In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman's rank correlation analysis to examine the association between POLH-AS1 expression and the tumor's immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. CONCLUSIONS: POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Proliferación Celular , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Movimiento Celular , Células Hep G2

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PURPOSE: To evaluate outcomes including safety and efficacy of drug-eluting bead trans-arterial chemo-embolization (DEB-TACE) in the treatment of locally advanced hepatocellular carcinoma (LA-HCC). MATERIALS AND METHODS: In this single-center, retrospective study, we evaluated 471 consecutive patients with LA-HCC who underwent DEB-TACE from 2015 to 2020. Efficacy of DEB-TACE was assessed based on the imaging response using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the biochemical response using alpha-fetoprotein (AFP) levels at 1-month follow-up. Adverse events, progression free survival (PFS), and overall survival were also examined. RESULTS: HCC distribution was bilobar in 49% with largest lesion mean size of 4.3 cm ± 3.2, and a majority of patients (46.7%) were Barcelona Club Liver Cancer (BCLC) stage B. Complete radiologic response was achieved in 120 (25.5%) patients, comparable to a reported 28% rate for conventional TACE. Biochemically, 41 (8.7%) patients achieved complete response, and 113 (24%) had a partial response. A total of 59 (12.5%) patients were successfully bridged to liver transplantation. Major adverse events were observed in 3%, while 7.2% experienced post-embolization syndrome. Mean PFS was 6.7 months ± 6.6, and overall survival was 64%, 16.3%, 2.1% at 1, 3, and 5 years, respectively. CONCLUSION: Based on our real world experience at a single center, DEB-TACE remains the locoregional therapy of choice for LA-HCC due to its favorable safety and efficacy profile.

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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Quimioembolización Terapéutica/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis

RESUMEN

BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Receptores Inmunológicos , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Masculino , Femenino , Pronóstico , Receptores Inmunológicos/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Quimioembolización Terapéutica/métodos , Anciano , Linfocitos T/inmunología , Linfocitos T/metabolismo , Adulto , Receptores Virales/metabolismo

RESUMEN

Objective: To examine the effects of peripheral blood eosinophil (EOS) count and its dynamic alterations on the treatment efficacy and prognosis of patients with advanced hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) receiving camrelizumab combined with lenvatinib (C + L) therapy. Methods: A retrospective analysis was performed on 200 patients with advanced HBV-HCC who were admitted to two centers from January 2018 to August 2023 and treated with C + L. EOS, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were determined before C + L treatment (EOS0, NLR0, and PLR0) and after three cycles of treatment (EOS3, NLR3, and PLR3). The area under the curve was calculated using the receiver operating characteristic (ROC) curve. NLR and PLR served as references to analyze the effect of differences in EOS in predicting the survival efficacy of patients with HBV-HCC treated using C + L. The independent risk factors affecting progression-free survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate Cox proportional risk models. Results: The ROC curve revealed that the predictive value of EOS3 was better than those of NLR3 and PLR3 for the long-term treatment efficacy of patients with intermediate and advanced HBV-HCC receiving C + L. Statistically significant differences were observed between groups with different levels of EOS0 and EOS3 and the evaluation of treatment efficacy after 3 weeks (P < 0.05). The median PFS of the high-EOS0 group was higher than that of the low-EOS0 group (P = 0.027); median PFS of the high EOS3 group was higher than that of the low EOS3 group (P = 0.018); median OS of the high EOS0 group was higher than that of the low EOS0 group (P = 0.032); median OS of the high EOS3 group was higher than that of the low EOS3 group (P < 0.0001). Multifactorial Cox analysis revealed that EOS3 was an independent predictor of PFS and that EOS0 was an independent predictor of OS (P < 0.05). Conclusion: EOS may be an ideal indicator for predicting the treatment efficacy and prognosis of patients with advanced HBV-HCC receiving C + L.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Eosinófilos , Hepatitis B , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/sangre , Femenino , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Curva ROC , Anciano , Recuento de Leucocitos , Adulto , Virus de la Hepatitis B/aislamiento & purificación , Resultado del Tratamiento

RESUMEN

Objectives: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection. Methods: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented. Results: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted. Conclusion: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments.

Asunto(s)

Neoplasias Colorrectales , Neoplasias Hepáticas , Mutación , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Biomarcadores de Tumor/genética , Pronóstico , Hepatectomía/métodos , Proteínas Proto-Oncogénicas B-raf/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteína Smad4/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía

RESUMEN

BACKGROUND: The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability. METHODS: This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP. RESULTS: A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03). CONCLUSIONS: CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP.

Asunto(s)

Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Mutación , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Hepatectomía/métodos , Pronóstico , Tasa de Supervivencia , Anciano , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Adulto , Biomarcadores de Tumor/genética

RESUMEN

BACKGROUND: Evaluation of the influence of the age of the patients upon the outcomes of liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent LR between 2010 and 2020 were analyzed. They were divided into 3 groups depending on the patient's age. Group I (patients less than 60 years), Group II (patients between 60 and 69 years), and Group III (patients equal to or more than 70 years). RESULTS: 364 patients were included. A significantly higher serum bilirubin and alpha feto-protein were noted in Group I and serum creatinine was noted in Group III. The study groups did not show any significant differences regarding HCC site, number, macrovascular invasion, the extent of LR, Pringle maneuver, and perioperative blood transfusions. Longer operation time was found in Groups II and III, while more blood loss was noted in Group (I) Group I patients had longer hospital stays. Higher postoperative morbidities were noted in both Group I and Group (II) Higher incidence of post-hepatectomy liver dysfunction was noted in Group I. More early mortalities were found in Group I, related to liver failure. We did not experience early mortality in Group (III) Late Mortalities occurred in 117 patients (32.1%). HCC recurrence occurred in 165 patients (45.3%). Regarding the overall- and tumor-free survival, we did not experience any significant differences among the 3 groups (Log Rank: p = 0.371 and 0.464 respectively). CONCLUSIONS: Curative LR can be safely performed in selected elderly patients with HCC. An advanced patient's age should not be considered as a contraindication for curative LR.

Asunto(s)

Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Hepatectomía/métodos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Factores de Edad , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Adulto , Tempo Operativo , Tiempo de Internación/estadística & datos numéricos

RESUMEN

INTRODUCTION: Liver cancer (LC) is frequently preceded by cirrhosis and poses a significant public health challenge in the United States (US). Recent decades have seen notable shifts in the epidemiological patterns of LC, yet national data guiding the optimal allocation of resources and preventive efforts remain limited. This study aims to investigate the current trends, risk factors, and outcomes of LC in the US. METHODS: This study utilized the Global Burden of Disease (GBD) dataset to collect data on the annual incident cases, deaths, Disability-Adjusted Life Years (DALYs), age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized DALY rates of primary LC and its etiologies and risk factors, between 1990 and 2019. Percentage changes in incident cases, DALYs, and deaths and the estimated annual percentage change (EAPC) in ASIR and deaths rates of LC were calculated to conduct temporal analysis. Linear regression was applied for the calculation of EAPCs. Correlations of EAPC with socio-demographic index (SDI) were separately evaluated by Pearson correlation analyses. RESULTS: We observed a marked increase in the ASIR of LC, increasing from 2.22 (95% CI: 2.15-2.27) per 100,000 people in 1990 to 5.23 (95% CI: 4.28-6.29) per 100,000 people in 2019, a percentage change of 135.4%. LC due to hepatitis C followed by alcohol use were the primary factors driving this increase. The ASIR and age-standardized death rates of LC showed a significant average annual increase of 3.0% (95% CI: 2.7-3.2) and 2.6% (95% CI: 2.5-2.8), respectively. There was a significant negative correlation between the SDI and the EAPC in ASIR (ρ = -0.40, p = 0.004) and age-standardized death rates (ρ = -0.46, p < 0.001). In 2019, drug and alcohol use, followed by elevated body mass index (BMI) were the primary risk factors for age-standardized DALY rates attributable to LC. CONCLUSION: The increased burden of LC in the US highlights the need for interventions. This is particularly important given that LC is mostly influenced by modifiable risk factors, such as drug and alcohol use, and elevated BMI. Our findings highlight the urgent need for public health interventions targeting socio-economic, lifestyle, and modifiable risk factors to mitigate the escalating burden of LC.

Asunto(s)

Neoplasias Hepáticas , Humanos , Estados Unidos/epidemiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Factores de Riesgo , Incidencia , Persona de Mediana Edad , Carga Global de Enfermedades/tendencias , Años de Vida Ajustados por Discapacidad , Anciano , Adulto , Costo de Enfermedad , Años de Vida Ajustados por Calidad de Vida

RESUMEN

Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1-3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1-3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0-2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1-2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Aspirina , Bevacizumab , Carcinoma Hepatocelular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insulina , Neoplasias Hepáticas , Metformina , Compuestos de Fenilurea , Quinolinas , Humanos , Metformina/uso terapéutico , Metformina/administración & dosificación , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Anciano , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Pronóstico , Insulina/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más Años

RESUMEN

RATIONALE: Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. OBJECTIVES: To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. ELIGIBILITY CRITERIA: Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis. OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious. RISK OF BIAS: We assessed risk of bias using the RoB 2 tool. SYNTHESIS METHODS: We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE. INCLUDED STUDIES: We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years. SYNTHESIS OF RESULTS: Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials. AUTHORS' CONCLUSIONS: Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014869.

Asunto(s)

Antineoplásicos Hormonales , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamoxifeno , Humanos , Tamoxifeno/uso terapéutico , Tamoxifeno/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Femenino , Adulto , Calidad de Vida , Masculino , Sesgo , Causas de Muerte , Persona de Mediana Edad , Progresión de la Enfermedad

RESUMEN

No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend < 0.001). HBV antiviral therapy was increased and improved OS and RFS in patients treated using RFA. The outcomes after RFA over a 20-year period improved due to changes over time in target tumors and patients. The results could be useful for selecting patients who will benefit from RFA.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/epidemiología , Adulto , Estimación de Kaplan-Meier