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BACKGROUND: Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. METHODS: A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. RESULTS: Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. CONCLUSION: Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatectomía/efectos adversos , Humanos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Portal vein tumor thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch of the main portal vein (MPV) or above could benefit from negative margin (R0) liver resection (LR). An Eastern Hepatobiliary Surgery Hospital (EHBH)/PVTT scoring system was established to predict the prognosis of HCC patients with PVTT after R0 LR and guide selection of subgroups of patients that could benefit from LR. HCC patients with PVTT limited to a first-order branch of the MPV or above who underwent R0 LR as an initial therapy were included. The EHBH-PVTT score was developed from a retrospective cohort in the training cohort using a Cox regression model and validated in a prospective internal validation cohort and three external validation cohorts. There were 432 patients in the training cohort, 285 in the prospective internal validation cohort, and 286, 189, and 135 in three external validation cohorts, respectively. The score was calculated using total bilirubin, α-fetoprotein (AFP), tumor diameter, and satellite lesions. The EHBH-PVTT score differentiated two groups of patients (≤/>3 points) with distinct long-term prognoses (median overall survival [OS], 17.0 vs. 7.9 months; P < 0.001). Predictive accuracy, as determined by the area under the time-dependent receiver operating characteristic curves (AUCs; 0.680-0.721), was greater than that of the other commonly used staging systems for HCC and PVTT. Conclusion: The EHBH-PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR. It selected appropriate HCC patients with PVTT limited to a first-order branch of the MPV or above for LR. It can be used to supplement the other HCC staging systems.
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Carcinoma Hepatocelular/cirugía , Técnicas de Apoyo para la Decisión , Hepatectomía , Neoplasias Hepáticas/cirugía , Trombosis/etiología , Adulto , Carcinoma Hepatocelular/complicaciones , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Vena Porta , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). METHODS: The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). CONCLUSION: Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombosis , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/cirugía , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Estudios Retrospectivos , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/cirugíaRESUMEN
BACKGROUND: Microvascular invasion (MVI) is associated with poor postoperative survival outcomes in patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis in patients with HCC with MVI after R0 liver resection (LR) and to supplement the most commonly used classification systems. MATERIALS AND METHODS: Patients with HCC with MVI who underwent R0 LR as an initial therapy were included. The EHBH-MVI score was developed from a retrospective cohort from 2003 to 2009 to form the training cohort. The variables associated with overall survival (OS) on univariate analysis were subsequently investigated using the log-rank test, and the EHBH-MVI score was developed using the Cox regression model. It was validated using an internal prospective cohort from 2011 to 2013 as well as three independent external validation cohorts. RESULTS: There were 1,033 patients in the training cohort; 322 patients in the prospective internal validation cohort; and 493, 282, and 149 patients in the three external validation cohorts, respectively. The score was developed using the following factors: α-fetoprotein level, tumor encapsulation, tumor diameter, hepatitis B e antigen positivity, hepatitis B virus DNA load, tumor number, and gastric fundal/esophageal varicosity. The score differentiated two groups of patients (≤4, >4 points) with distinct long-term prognoses outcomes (median OS, 55.8 vs. 19.6 months; p < .001). The predictive accuracy of the score was greater than the other four commonly used staging systems for HCC. CONCLUSION: The EHBH-MVI scoring system was more accurate in predicting prognosis in patients with HCC with MVI after R0 LR than the other four commonly used staging systems. The score can be used to supplement these systems. IMPLICATIONS FOR PRACTICE: Microvascular invasion (MVI) is a major determinant of survival outcomes after curative liver resection for patients with hepatocellular carcinoma (HCC). Currently, there is no scoring system aiming to predict prognosis of patients with HCC and MVI after R0 liver resection (LR). Most of the widely used staging systems for HCC do not use MVI as an independent risk factor, and they cannot be used to predict the prognosis of patients with HCC and MVI after surgery. In this study, a new Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis of patients with HCC and MVI after R0 LR. Based on the results of this study, postoperative adjuvant therapy may be recommended for patients with HCC and MVI with an EHBH-MVI score >4. This score can be used to supplement the currently used HCC classifications to predict postoperative survival outcomes in patients with HCC and MVI.
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Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Femenino , Hospitales , Humanos , Neoplasias Hepáticas/patología , Masculino , Invasividad Neoplásica , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Vascular invasion is a major determinant of survival outcomes after curative resection for hepatocellular carcinoma (HCC) patients. This study was designed to investigate the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with HCC with hepatic vein tumor thrombus (HVTT). METHODS: Data from patients who underwent LR for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-TACE after LR were compared with those who underwent LR alone. Propensity score matching (PSM) analysis was performed to match patients in a ratio of 1:1. RESULTS: All included 319 patients who underwent LR for HCC with HVTT, 134 underwent LR alone (the LR group), and 185 patients underwent in adjuvant TACE (the PA-TACE group). PSM matched 107 patients in two groups. The overall survival (OS) and recurrence-free survival (RFS) were significantly better for patients in the PA-TACE group than the LR group (for OS: before PSM, P < 0.001; after PSM, P = 0.004; for RFS: before PSM, P < 0.001; after PSM, P = 0.013), respectively. On subgroup analysis, equivalent acceptable results were obtained in patients with peripheral HVTT (pHVTT) and major HVTT (mHVTT). However, PA-TACE resulted in no survival benefits for patients when the HVTT had extended to the inferior vena cava (IVCTT). CONCLUSIONS: PA-TACE was associated with significantly better survival outcomes than LR alone for patients with HCC and HVTT (pHVTT and mHVTT). There was no survival benefits in patients whose HVTT had extended to form IVCTT.
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Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/mortalidad , Hepatectomía/mortalidad , Venas Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Cuidados Posoperatorios , Adyuvantes Inmunológicos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Venas Hepáticas/patología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Microvascular invasion (MVI) predicts poor prognosis in patients with hepatocellular carcinoma (HCC). HCC patients with hypercoagulability are prone to develop thrombosis; however, the relationship between preoperative coagulability state, as reflected by the international normalized ratio (INR) level, and MVI remains unclear. METHODS: From January 2009 to December 2012, HCC patients who underwent R0 liver resection (LR) from four cancer centers entered into this study. The overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the 2509 HCC patients who were included into this study, 1104 were found to have MVI in the resected specimens. These patients were divided into the low (n = 151), normal (n = 796), and high (n = 157) INR subgroups based on the preoperative INR levels. The low INR subgroup had a significantly higher incidence of MVI than the normal or high INR subgroups (61.6% vs. 41.6% vs. 44.6%; p < 0.001). HCC patients with MVI were significantly more likely to have a low preoperative INR level (p < 0.001); the INR level (p < 0.001) was an independent risk factor of OS and RFS. HCC patients with MVI in the low INR subgroup had significantly worse RFS and OS than the normal or high INR subgroups (median RFS 13.5 vs. 20.2 vs. 21.6 months, p < 0.001; median OS 35.5 vs. 59.5 vs. 57.0 months, p < 0.001). CONCLUSIONS: Preoperative hypercoagulability was associated with poor long-term prognosis in HCC patients with MVI after R0 LR.
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Carcinoma Hepatocelular/patología , Hepatectomía/mortalidad , Neoplasias Hepáticas/patología , Microvasos/patología , Recurrencia Local de Neoplasia/patología , Trombofilia/mortalidad , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/irrigación sanguínea , Recurrencia Local de Neoplasia/cirugía , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trombofilia/fisiopatologíaRESUMEN
AIM: Because of the rarity of hepatic vein tumor thrombus (HVTT) in patients with hepatocellular carcinoma (HCC), little is known about HVTT. Thus, the survival benefit of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) for HCC patients with HVTT or inferior vena cava tumor thrombus (IVCTT) remains controversial. We aimed to explore the survival benefits of LR versus TACE for the treatment of these patients. METHODS: From 2012 to 2016, a total of 276 patients with HVTT or IVCTT who underwent liver resection or TACE were enrolled in this study. Patients in the LR group were matched at a 1:1 ratio with patients treated with TACE as an initial treatment (TACE group). Clinical characteristics, overall survival, and disease-free survival were analyzed. RESULTS: The median survival time in the LR group was 4.7 months longer than that in the TACE group before PSM (19.4 vs. 14.7 months, P = 0.006) and 6.9 months longer than that in the TACE group after PSM (20.9 vs. 14.0 months, P = 0.019). The median disease-free survival time in the LR group was 3.2 months longer than that in the TACE group before PSM (12.3 vs. 9.1 months, P = 0.038) and 5.8 months longer than that in the TACE group after PSM (13.0 vs. 7.2 months, P = 0.011). CONCLUSION: Liver resection provides a good prognosis for HCC patients with HVTT or IVCTT compared with patients undergoing TACE, and coexistence with portal vein tumor thrombus is the most important factor related to survival.
RESUMEN
BACKGROUND: The effect of microvascular invasion (MVI) on the postoperative long-term prognosis of solitary small hepatocellular carcinoma remains controversial. We compared the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma. METHODS: The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma from inception to November 1, 2018. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS: Fourteen studies involving 3033 patients were evaluated. A meta-analysis of all 14 studies suggested that the OS of the MVI-positive group was significantly worse than that of the MVI-negative group (HR = 2.39, 95% CI = 2.02-2.84, I2 = 22.8%; P < 0.001). Twelve studies were included in the meta-analysis of DFS, and MVI showed a worse prognosis (HR = 1.79, 95% CI = 1.59-2.02, I2 = 25.3%; P < 0.001). Subgroup analysis demonstrated that MVI still showed a negative effect on the long-term OS and DFS of patients with solitary small HCC measuring up to 2 cm, 3 cm, or 5 cm. CONCLUSION: Microvascular invasion was a risk factor for poorer prognosis for solitary small hepatocellular carcinoma.
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Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Causas de Muerte , Hepatectomía/mortalidad , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Anciano , Carcinoma Hepatocelular/cirugía , China , Femenino , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/cirugía , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). METHODS: The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. RESULTS: 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. CONCLUSIONS: PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Sorafenib/uso terapéutico , Adulto , Quimioterapia Adyuvante , Femenino , Hepatectomía , Humanos , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Invasividad Neoplásica , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
IL-8 over-expression could enhance cancer metastasis. In present study, berberine hydrochloride (BER) triggered proliferative inhibition and G2/M arrest in AGS cells, down-regulated protein expression of cyclin B1, Bcl-2, up-regulated expression of p21, p53 and cleaved caspase 3, but showed no effect on protein expression of CHOP, Bip, and caspase 4. BER could down-regulate the enhanced IL-8 expression through down-regulating ERK1/2 and p38 MAPK over-activation induced by SN 38. The increased IL-8 mediated adhesive ability of AGS cells to HUVECs induced by SN 38, could be reduced by BER. Thus, BER could reduce the side-effect of SN 38 in clinic.
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Berberina/farmacología , Interleucina-8/antagonistas & inhibidores , Interleucina-8/biosíntesis , Irinotecán/antagonistas & inhibidores , Irinotecán/farmacología , Inhibidores de Topoisomerasa I/farmacología , Proteínas Reguladoras de la Apoptosis/biosíntesis , Adhesión Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidoresRESUMEN
Robo1 is a member of the Robo immunoglobulin superfamily of proteins, and it plays an important role in angiogenesis and cancer. In this study, we investigate the role of roundabout 1 (Robo1) in tumor angiogenesis in hepatocellular carcinoma (HCC). Firstly, the relationship between Robo1 expression on tumors and patient's survival and endothelial cells in tumor blood vessels and patient's survival was studied. Secondly, Robo1 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). Cell proliferation, motility, and tube formation were compared in HUVEC with different Robo1 expression. Also, HUVECs with different Robo1 expression were mixed with HCCLM3 and HepG2 hepatoma cells and then implanted in a nude mouse model to examine the effects of Robo1 in endothelial cells on tumor growth and angiogenesis. Cell motility-related molecules were studied to investigate the potential mechanism how Robo1 promoted tumor angiogenesis in HCC. The disease-free survival of the patients with high Robo1 expression in tumoral endothelial cells was significantly shorter than that of those with low expression (P = 0.021). Overexpression of Robo1 in HUVECs resulted in increased proliferation, motility, and tube formation in vitro. In the implanted mixture of tumor cells and HUVECs with an increased Robo1 expression, tumor growth and microvessel density were enhanced compared with controls. Robo1 promoted cell division cycle 42 (Cdc42) expression in HUVECs, and a distorted actin cytoskeleton in HUVECs was observed when Robo1 expression was suppressed. In conclusion, Robo1 promoted angiogenesis in HCC mediated by Cdc42.
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Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Neovascularización Patológica/genética , Proteínas del Tejido Nervioso/biosíntesis , Receptores Inmunológicos/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Animales , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas del Citoesqueleto , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones , Persona de Mediana Edad , Neovascularización Patológica/patología , Proteínas del Tejido Nervioso/genética , Receptores Inmunológicos/genética , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de Unión al GTP rho , Proteínas RoundaboutRESUMEN
Endothelial cells (ECs) are critical for angiogenesis, and microRNAs play important roles in this process. We investigated the regulatory role of microRNAs in ECs of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-146a as the most highly upregulated microRNA. Furthermore, we revealed that miR-146a promoted the expression of platelet-derived growth factor receptor α (PDGFRA) in HUVECs, and this process was mediated by BRCA1. Overexpression of PDGFRA in the ECs of HCC tissues was associated with microvascular invasion and predicted a poorer prognosis. These results suggest that miR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a-BRCA1-PDGFRA pathway. MiR-146a and PDGFRA may emerge as potential anti-angiogenic targets on ECs for HCC therapy.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Proteína BRCA1/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Regulación Neoplásica de la Expresión Génica/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal/genética , Regulación hacia ArribaRESUMEN
Antiangiogenic therapy, specially sorafenib, has become the standard of care for patients with advanced hepatocellular carcinoma (HCC), however, the improvement in survival time is not satisfactory. Previous studies have found that, in some circumstances, antiangiogenic therapy promoted tumor metastasis and the mechanistic studies were mainly focus on cancer-cell-autonomous manners. In two experimental metastasis models with tail-vein injection with hepatoma cells and an orthotopic HCC mouse model, we found that pretreatment with two vascular endothelial growth factor receptor (VEGFR) inhibitors, sunitinib and sorafenib, facilitated tumor cell survival in blood stream and promoted lung metastasis from tumors that were subsequently incubated after drug discontinuation, indicating that host response joined into the pro-metastatic effects. An antibody microarray identified that interleukin (IL)-12b was decreased in the peripheral blood of the mice treated with the two VEGFR inhibitors. IL-12b suppression in macrophages and dendritic cells from host organs was found to play a crucial role in treatment-induced metastasis. Supplement with recombinant mouse IL-12b or restoration of IL-12b expression in the host by zoledronic acid, which was previously reported to enhance IL-12 expression in vitro and in vivo, alleviated the metastasis-promoting effects of sunitinib and sorafenib. These studies suggest that host response to VEGFR inhibitors facilitates HCC metastasis and restoration of IL-12b expression could translate into clinical benefits.
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Inhibidores de la Angiogénesis/toxicidad , Carcinoma Hepatocelular/secundario , Indoles/toxicidad , Subunidad p40 de la Interleucina-12/fisiología , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Niacinamida/análogos & derivados , Compuestos de Fenilurea/toxicidad , Pirroles/toxicidad , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacología , Animales , Carcinoma Hepatocelular/irrigación sanguínea , Línea Celular Tumoral , Células Dendríticas/inmunología , Difosfonatos/uso terapéutico , Xenoinjertos , Humanos , Imidazoles/uso terapéutico , Terapia de Inmunosupresión , Indoles/administración & dosificación , Indoles/farmacología , Subunidad p40 de la Interleucina-12/deficiencia , Subunidad p40 de la Interleucina-12/genética , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/irrigación sanguínea , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Desnudos , Trasplante de Neoplasias , Células Neoplásicas Circulantes , Neovascularización Patológica/tratamiento farmacológico , Niacinamida/administración & dosificación , Niacinamida/farmacología , Niacinamida/toxicidad , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/farmacología , Pirroles/administración & dosificación , Pirroles/farmacología , Sorafenib , Sunitinib , Ácido ZoledrónicoRESUMEN
BACKGROUND: Early and late recurrence of hepatocellular carcinoma (HCC) have different clinical outcomes, especially for those accompanied by microvascular invasion (MVI), but the definition of early recurrence remains controversial. Therefore, a reasonable identification of the early recurrence time for HCC is urgently needed. METHODS: Resected recurrence patients were enrolled and divided into two cohorts, one for identification of the early recurrence time and another for verification of the accuracy of the point. Univariable and multivariable Cox regression analyses were adopted to identify the prognostic factors of recurrence HCC (rHCC) and Kaplan-Meier method was applied to analyze the overall survival (OS). The appropriate cutoff value was determined by the exhaustive method using different recurrence intervals from 1 to 24 months in turn. RESULTS: In total, 292 resected rHCC patients were analyzed to calculate the early recurrence interval, and another 421 resected rHCC patients with MVI were enrolled to verify the efficacy of adjuvant transarterial chemoembolization (TACE) in this recurrence interval. MVI was identified as an independent risk factor by multivariable analysis. The OS of rHCC patients without MVI is better than that of patients with MVI when the recurrence time was within 13 months, while not beyond 13 months. The verification cohort demonstrated that adjuvant TACE provided longer survival for rHCC with MVI when the recurrence time was within 13 months, while not beyond 13 months. CONCLUSION: For HCC patients with MVI who underwent R0 resection, 13 months may be a reasonable early recurrence time point, and within this interval, postoperative adjuvant TACE may result in longer survival compared with surgery alone.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Quimioembolización Terapéutica/métodos , Invasividad Neoplásica , Hepatectomía , Adyuvantes Inmunológicos , Recurrencia Local de Neoplasia/patologíaRESUMEN
BACKGROUND: This multicenter-based retrospective study aimed to investigate the prognostic factors and report our experiences with the diagnosis and treatment of hepatic epithelioid hemangioendothelioma (HEHE), a rare malignant vascular tumor. METHODS: A total of 33 patients with HEHE from two centers between 2004 and 2011 were retrospectively reviewed with respect to their clinical, radiologic, and pathologic characteristics; treatment modalities and outcomes; and potential prognostic factors. RESULTS: A total of 17 patients underwent liver resections (LRs) alone, 12 patients had transcatheter arterial chemoembolization (TACE) alone, three patients had LR followed by TACE, and one patient underwent liver transplantation (LT). The difference of overall survival (OS) between LR and TACE was not significant (p = 0.499). Older patients [≥47 years, n = 17; p = 0.035, hazard ratio (HR) = 7.0), those with symptoms (n = 17; p = 0.001, HR = 86.5], and those with an elevated serum CA19-9 level (>37 U/ml, n = 5; p = 0.018, HR = 5.0) had a poorer OS, according to univariate analysis. The presence of symptoms was validated as a prognostic factor (p = 0.012) by multivariate analysis. CONCLUSIONS: Liver resection and TACE have comparable outcomes in HEHE patients. The presence of symptoms indicates a poor prognosis. Older age and elevated serum CA19-9 are potential negative impact factors on outcome.
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Hemangioendotelioma Epitelioide , Neoplasias Hepáticas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The aim of this study is to evaluate the long-term prognosis of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) in these patients. Methods: Data from HCC patients with BDTT who underwent liver resection and TACE were analyzed respectively. Propensity score matching (PSM) analysis was performed in these patients. Results: A total of 145 HCC patients with BDTT were divided into two groups: the LR group (n = 105) and the TACE group (n = 40). The median OS in the LR group was 8.0 months longer than that in the TACE group before PSM (21.0 vs. 13.0 months, P <0.001) and 9.0 months longer after PSM (20.0 vs. 11.0 months, P <0.001). The median DFS in the LR group was 3.5 months longer than that in the TACE group before PSM (7.0 vs. 3.5 months, P = 0.007) and 5 months longer after PSM (7.0 vs. 2.0 months, P = 0.007). Conclusion: If surgery is technically feasible, liver resection provides better prognosis for HCC patients with BDTT compared with TACE.
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Purpose: This study aimed to assess the efficacy and safety of a triple therapy that comprises transarterial chemoembolization (TACE), antiangiogenic-targeted therapy, and programmed death-1 (PD-1) inhibitors in a real-world cohort of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: Consecutive patients treated with TACE combined with antiangiogenic therapy and PD-1 inhibitors at the Eastern Hepatobiliary Surgery Hospital between June 2019 and May 2021 were enrolled. The baseline characteristics and treatment course of the patients were recorded. The tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST). The overall survival (OS) and progression-free survival (PFS) of the patients were analyzed using the Kaplan-Meier method. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: As of the data cutoff on 30 August 2021, the median follow-up time was 10.0 (3.9-28.4) months. A total of 39 eligible patients were included. The objective response rate (ORR) and the disease control rate (DCR) were 35.9% and 74.4% according to the RECIST 1.1, and 48.7% and 84.6% according to mRECIST criteria, respectively. The median OS and PFS were 14.0 and 9.2 months, respectively. Moreover, 34 (87.2%) patients experienced at least one treatment-related AE and 8 (20.5%) patients experienced grade 3/4 treatment-related AEs. The most common treatment- and laboratory-related AEs were hypertension (46.2%) and decreased albumin (53.8%), respectively. No treatment-related mortality occurred during the study period. Conclusions: TACE combined with antiangiogenic-targeted therapy and immune checkpoint inhibitors may have promising anticancer activity in unresectable HCC patients with PVTT. AEs were manageable, with no unexpected overlapping toxicities.
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BACKGROUND: Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS: Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS: Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.
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Carcinoma Hepatocelular/patología , Diabetes Mellitus Tipo 2/epidemiología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/patología , Microvasos/patología , Adulto , Anciano , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/cirugía , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Previous studies have demonstrated that tyroserleutide (YSL) inhibits tumor growth in an animal model of hepatocellular carcinoma (HCC). However, its effects on HCC metastasis are still not fully understood. To examine YSL as a novel agent to prevent HCC metastasis, a metastatic human HCC orthotopic nude mouse model of MHCC97L was used. The antitumor and antimetastasis effects of YSL were also evaluated in combination with radiation. Hypoxia and epithelial-mesenchymal transition (EMT)-related molecules were studied. YSL inhibited MHCC97L cell invasion in vitro with or without irradiation. YSL did not significantly inhibit tumor growth but decreased pulmonary metastasis and prolonged life-span for more than 40 days, which correlated with down-regulation of matrix metalloproteinase-2. Radiotherapy inhibited early-stage tumor growth and promoted tumor hypoxia. The re-implanted tumor volume in the radiotherapy group was not significantly different from the control, in which the incidence of lung metastasis increased after radiotherapy (6/6 versus 3/6, P = 0.046); however, YSL inhibited the growth of re-implanted tumor after radiotherapy. Furthermore, YSL at 160 or 320 µg/kg/day almost completely inhibited lung metastasis induced by irradiation (1/6 versus 6/6, P = 0.002 for both dosages). YSL down-regulated hypoxia-inducible factor 1α (HIF-1α) and transmembrane protease serine 4 (TMPRSS4), and inhibited EMT was associated with the antimetastasis capability of YSL. Our data suggest that YSL inhibits the enhanced invasiveness and metastatic potential of HCC induced by irradiation through down-regulation of HIF-1α and TMPRSS4 and inhibition of EMT. YSL may have potential as a new antimetastasis agent for radiotherapy.