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PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Artéria Hepática/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Infusões Intra-ArteriaisRESUMO
OBJECTIVE: To investigate the effect of modified Vattikuti Institute prostatectomy (mVIP) in the treatment of localized PCa. METHODS: This retrospective study included 50 cases of localized PCa treated by mVIP and another 50 by robot-assisted radical prostatectomy (RARP) from March 2018 to April 2019. We analyzed the baseline data, the surgical techniques used and the results of short-term follow-up. RESULTS: All the operations were completed successfully without conversion to open surgery. The mVIP group, compared with the RARP, showed longer operation time (ï¼»90.35 ± 24.22ï¼½ vs ï¼»84.46 ± 19.18ï¼½ min, P > 0.05), more intraoperative blood loss (ï¼»220.00 ± 15.10ï¼½ vs ï¼»215.00 ± 15.10ï¼½ ml, P > 0.05), shorter postoperative hospital stay (ï¼»5.75 ± 1.45ï¼½ vs ï¼»6.20 ± 1.50ï¼½ d, P > 0.05), and higher rates of positive surgical margins (22.00% vs 14.00%, P > 0.05) and urinary continence at 1 month (76%vs 22%,P < 0.05), 6 months (84% vs 79%, P > 0.05) and 12 months after surgery (96% vs 94%, P > 0.05). CONCLUSIONS: Modified VIP can better preserve the lateral and posterolateral prostatic fascial tissue in the treatment of localized PCa and therefore significantly promote the recovery of urinary continence after surgery.
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Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Duração da Cirurgia , Próstata/cirurgia , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: ⢠TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. ⢠A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. ⢠The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Estadiamento de Neoplasias/métodos , Nomogramas , Terapia por Radiofrequência/métodos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Non-small-cell lung cancer (NSCLC) is the predominant form of lung cancer, and it is regulated by a complex signal transduction network. Single-agent targeted therapy often results in acquired resistance, which leads to treatment failure. In this study, we demonstrated that a combination of the kinase inhibitors trametinib and bosutinib can synergistically suppress the growth of NSCLC by inhibiting both the mitogen-activated protein kinase (MAPK) and proto-oncogene tyrosine-protein kinase (SRC) pathways. The combination was profiled against a panel of 22 NSCLC cell lines, including one erlotinib-resistant cell line, and this combination was found to show synergistic effects against 16 cell lines. NSCLC cell lines (HCC827, HCC827-erlotinib-resistant, and H1650) were treated with trametinib, bosutinib, or a combination of these drugs. The drug combination inhibited colony formation and induced cell apoptosis. A mechanism study showed that the phosphorylation of multiple kinases in the epidermal growth factor receptor (EGFR) signaling pathway in NSCLC was down-regulated. In addition, the combination significantly attenuated tumor growth of HCC827 xenografts with low toxicity. Our findings provide a theoretical basis for further study of the combination of MAPK and SRC pathway inhibitors in NSCLC, especially in the treatment of erlotinib-resistant NSCLC.
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Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.
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Técnicas de Ablação , Bilirrubina/sangue , Plaquetas , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Albumina Sérica/análise , Índice de Gravidade de Doença , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
SMYD3, a member that belongs to the SET and MYND-domain (SMYD) family, has also been proven to largely participate in gene transcription regulation and progression of several human cancers as a histone lysine methyltransferase. However, the role and significance of SMYD3 in both the clinic and progression of hepatocellular carcinoma (HCC) remain unclear. Herein, we find that SMYD3 is increased in cirrhotic livers, and strikingly upregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Subsequent analyses suggest that high expression level of SMYD3 significantly correlates with the malignant characteristics of HCC, and predicts poor prognosis in patients. Our results show that overexpression of SMYD3 increases, while silencing of SMYD3 inhibits, cell proliferation, invasiveness and tumorigenicity both in vitro and in vivo. SMYD3 also promotes intrahepatic metastasis of HCC cells. For the mechanisms, we identify that SMYD3 bound to CDK2 and MMP2 promoter and increased H3K4me3 modification at the corresponding promoters to promote gene transcription. Importantly, pharmacological targeting of SMYD3 with BCI-121 inhibitor effectively repressed the tumorigenicity of HCC cells. Finally, our results show that gene locus amplification is a cause for SMYD3 overexpression in HCC. These findings not only uncover that SMYD3 overexpression promotes the tumorigenicity and intrahepatic metastasis of HCC cell via upregulation of CDK2 and MMP2, but also suggest SMYD3 could be a practical prognosis marker or therapeutic target against the disease.
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Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Quinase 2 Dependente de Ciclina/genética , Amplificação de Genes , Histona-Lisina N-Metiltransferase/genética , Neoplasias Hepáticas/patologia , Metaloproteinase 2 da Matriz/genética , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/secundário , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Progressão da Doença , Feminino , Amplificação de Genes/fisiologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Ativação Transcricional , Células Tumorais Cultivadas , Regulação para Cima/genéticaRESUMO
F-652 is a recombinant fusion protein consisting of two human interleukin-22 (IL-22) molecules linked to an immunoglobulin constant region (IgG2-Fc). IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection. The safety, pharmacokinetics (PK), tolerability, and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized, double-blind, placebo-controlled study. Following single-dose subcutaneous (SC) injection of F-652 at 2.0 µg/kg into healthy subjects, six out of six subjects experienced delayed injection site reactions, which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing. F-652 was then administered to the healthy subjects via an intravenous (IV) infusion at 2.0, 10, 30, and 45 µg/kg. No severe adverse event (SAE) was observed during the study. Among the IV-dosed cohorts, eye and skin treatment emergent adverse events (TEAEs) were observed in the 30 and 45 µg/kg cohorts. F-652 IV dosing resulted in linear increases in Cmax and AUC(0-t), and the T1/2 ranged from 39.4 to 206 h in the cohorts. An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A, C-reactive protein, and FIB, and decreased serum triglycerides. The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45 µg/kg. In conclusion, IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties. These results warrant further clinical development of F-652 to treat inflammatory diseases.
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Infecções Bacterianas/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Cicatrização/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Citocinas/sangue , Dimerização , Relação Dose-Resposta a Droga , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Voluntários Saudáveis , Humanos , Regiões Constantes de Imunoglobulina/genética , Mediadores da Inflamação/sangue , Infusões Intravenosas , Reação no Local da Injeção/etiologia , Interleucinas/genética , Masculino , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacocinética , Proteína Amiloide A Sérica/metabolismo , Adulto Jovem , Interleucina 22RESUMO
PURPOSE: The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC). METHODS: Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group. CONCLUSION: TACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC.
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OBJECTIVE: To compare the clinical efficacy and safety of transcatheter hepatic arterial infusion chemotherapy (HAIC) with those of sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C. METHODS: Potentially relevant studies comparing the clinical efficacy and safety of HAIC with those of sorafenib were searched using Medline, PubMed, Embase, Cochrane Library, and Chinese databases (Wanfang Data and China National Knowledge Infrastructure). Overall survival rate (OSR), tumor response rate, disease control rate (DCR), and serious adverse events (SAEs) were compared and analyzed. Pooled ORs with 95% CIs were calculated using either the fixed-effects model or the random-effects model. All statistical analyses were conducted using Review Manager (version 5.3) from the Cochrane Collaboration. RESULTS: A total of 1,264 patients were included in this meta-analysis. The results of this study showed that HAIC was associated with significantly higher 1-, 2-, and 3-year OSRs than sorafenib (OR 1.88, 95% CI1-year: [1.27-2.78], P1-year=0.002; OR 2.15, 95% CI2-year: [1.06-4.37], P2-year=0.03; OR 7.90, 95% CI3-year: [2.12-29.42], P3-year=0.002). Compared to sorafenib, HAIC was associated with superior complete response (CR), partial response (PR), and objective response rate (ORR) (OR 3.90, 95% CICR: [1.89-8.03], P CR =0.0002; OR 3.47, 95% CIPR: [2.31-5.24], P PR <0.00001; OR 3.02, 95% CIOR: [2.05-4.45], P OR <0.0001). There was no statistically significant difference between HAIC and sorafenib in stable disease (SD), progressive disease (PD), DCR, and SAEs (OR 0.86, 95% CISD: [0.51-1.45], P SD =0.56; OR 0.62, 95% CIPD: [0.35-1.11], P PD =0.11; OR 0.53, 95% CISAE: [0.14-1.92], P SAE =0.33). CONCLUSION: This study showed that HAIC was associated with better efficacy than sorafenib in terms of OSR and tumor response. Therefore, HAIC can be considered as an alternative treatment option for patients with HCCs of BCLC stage C.
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Objective: To meta-analytically compare combined transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) and surgical resection (SR) for the treatment of hepatocellular carcinoma (HCC) within the Milan criteria. Materials and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for studies comparing these two therapies that were published between January 2006 and August 2017. Overall survival rate (OS), recurrence-free survival rate (RFS), major complications and the average length of hospital stay were compared between these two therapies. Meta-analytic pooled odds ratio (OR) was calculated using TACE plus RFA as the base category. Results: Seven case-control studies and one randomized trial were identified. Meta-analytic results revealed that, compared with SR, TACE plus RFA had significantly higher 1-year OS (OR for survival = 0.50, p = 0.009) and lower major complications (OR = 1.88, p = 0.02) after therapy. Three studies reported on the length of hospital stay. The average length ± standard deviation reported in individual studies for SR and TACE plus RFA groups was 19.8 ± 8.4 days and 7.4 ± 2.2 days, respectively; 18.7 ± 4.9 days and 11.5 ± 6.9 days, respectively; and 16.6 ± 6.7 days and 8.5 ± 4.1 days, respectively (p < 0.0001 for all studies). Three or 5-year OS and 1-, 3-, or 5-year RFS did not significantly differ between the two therapies. Conclusion: Combined TACE plus RFA may be an alternative to SR for the treatment of patients with HCC within Milan the criteria. Non-randomized design in most of the original studies was a limitation.
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Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência/métodos , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Tempo de Internação , Neoplasias Hepáticas/patologia , Masculino , Razão de Chances , Taxa de Sobrevida , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
PURPOSE: To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. METHODS: Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. RESULTS: All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19 months and the median survival time was 21 months (range 11-30 months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE. CONCLUSIONS: Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy.
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Quimioembolização Terapêutica/métodos , Sarcoma/terapia , Adulto , Quimioembolização Terapêutica/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma/irrigação sanguínea , Taxa de SobrevidaRESUMO
RATIONALE AND OBJECTIVE: The objective of this study was to analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stages B and C. MATERIALS AND METHODS: Clinical data of 198 patients with BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June 2012 and January 2017 were retrospectively collected and analyzed. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 11 prognostic factors potentially affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant. RESULTS: By the end of this study, the median follow-up duration was 43.6 months. The median overall survival (OS) of the patients was 21.0 months (95% confidence interval [CI]: 16.94-25.05), and the 1-, 2-, 3- and 5-year OS rates were 72%, 43%, 28%, and 4%, respectively. Tumor size (χ2 = 33.607, P < 0.0001), tumor number (χ2 = 4.084, P = 0.043), Child-Pugh class (χ2 = 33.187, P < 0.0001), BCLC stage (χ2 = 50.224, P < 0.0001), portal vein tumor thrombus (χ2 = 88.905, P < 0.0001), Eastern Cooperative Oncology Group (ECOG) performance status (χ2 = 98.007, P < 0.0001), extrahepatic spread (χ2 = 34.980, P < 0.0001), TACE times (χ2 = 8.350, P = 0.015), and sorafenib treatment strategy (χ2 = 81.593, P < 0.0001) were found to be significantly associated with OS by univariate analysis. Multivariate analysis showed that BCLC stage (95% CI: 1.133-3.982, P = 0.019), extrahepatic spread (95% CI: 1.136-2.774, P = 0.012), and sorafenib treatment duration (95% CI: 0.352-0.574, P = 0.000) were independent prognostic factors associated with OS. There were no serious treatment-related adverse events. CONCLUSIONS: This study showed that extrahepatic spread was a risk factor, and sorafenib treatment and superior BCLC stage were protective factors. Therefore, the study indicated that TACE combined with sorafenib was an effective and safe treatment for patients with BCLC stage B HCC without extrahepatic spread.
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Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/secundário , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Veia Porta/patologia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
PURPOSE: To study whether transarterial embolization (TAE) with RNA interference (RNAi) targeting hypoxia-inducible factor-1α (HIF-1α) can improve efficacy of TAE in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: CBRH-7919 rat hepatoma cell line was used and HCC models of rats were constructed. The siRNA transfection compound was made by mixing specific siRNA and Lipofectamine 2000™. Delivery and transfection of siRNA were administered by injecting iodized oil emulsion (diluted lipiodol and siRNA) via hepatic artery. The expression levels of mRNA and protein were detected using the real-time reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting assays, respectively. RESULTS: In vitro experiment, the specific HIF-1α-siRNA was proved to inhibit expression levels of HIF-1α and vascular endothelial growth factor (VEGF) effectively. In animal study, real-time RT-PCR assay showed the average relative mRNA expressions of HIF-1α were 0.31 ± 0.01, 0.65 ± 0.03, 0.46 ± 0.005, and 1.00 ± 0.00 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Western blotting assay showed the average relative protein expressions of HIF-1α were 0.13 ± 0.02, 0.87 ± 0.02, 0.39 ± 0.02, and 1.02 ± 0.01 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Compared with control, TAE, and siRNA groups, TAE + siRNA can significantly inhibit protein expressions of HIF-1α and VEGF (P HIF-1α < 0.001; P VEGF < 0.001). Overall survival of rats underwent TAE + siRNA was significantly longer than that of rats treated with TAE monotherapy (P = 0.001). CONCLUSION: This animal study showed TAE combined with HIF-1α-RNAi could significantly improve efficacy of TAE in treating HCC by inhibiting expressions of HIF-1α and VEGF after TAE treatment.
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Carcinoma Hepatocelular/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas Experimentais/terapia , Neoplasias Pulmonares/prevenção & controle , RNA Interferente Pequeno/genética , Animais , Carcinoma Hepatocelular/secundário , Linhagem Celular Tumoral , Embolização Terapêutica , Expressão Gênica , Técnicas de Silenciamento de Genes , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Pulmonares/secundário , Interferência de RNA , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer diagnosed by prostate biopsy, and eventually treated with laparoscopic radical prostatectomy. The prognostic impact of age, prostate volume, preoperative prostate-specific antigen, biopsy Gleason score, maximum percentage tumor per core, number of positive cores, biopsy perineural invasion, capsule invasion on imaging, and tumor laterality on surgical margin was assessed. The overall positive surgical margin rate was 29.1%. Gleason score, number of positive cores, perineural invasion, tumor laterality in the biopsy specimen, and prostate volume significantly correlated with risk of positive surgical margin by univariate analysis (P < 0.05). Gleason score (odds ratio [OR] = 2.286, 95% confidence interval [95% CI] = 1.431-3.653, P = 0.001), perineural invasion (OR = 4.961, 95% CI = 2.656-9.270, P < 0.001), and number of positive cores (OR = 4.403, 95% CI = 1.878-10.325, P = 0.001) were independent predictors of positive surgical margin at the multivariable logistic regression analysis. Patients with perineural invasion, higher biopsy Gleason scores and/or a large number of positive cores in biopsy pathology had more possibility of capsule invasion. The positive surgical margin rate in patients with capsule invasion (49.5%) was much higher than that with localized disease (17.8%). In contrast, prostate volume showed a protective effect against positive surgical margin (OR = 0.572, 95% CI = 0.346-0.945, P = 0.029). Gleason score, perineural invasion, and number of positive cores in the biopsy specimen were preoperative independent predictors of positive surgical margin after laparoscopic radical prostatectomy while prostate volume was a protective factor against positive surgical margin.
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Biópsia por Agulha/estatística & dados numéricos , Laparoscopia/métodos , Gradação de Tumores/estatística & dados numéricos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Próstata/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the application of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) in the treatment of early-stage prostate cancer. METHODS: We retrospectively analyzed the clinical data about 10 cases of early-stage prostate cancer treated by RS-RARP with the Da Vinci Robot Surgical System from September to October 2016. RESULTS: All the operations were successfully completed without positive surgical margins. The operation time was 170ï¼250 min (ï¼»196±25ï¼½ min), the intraoperative blood loss was 150ï¼500 ml (ï¼»260±128ï¼½ ml), the postoperative hospital stay was 6ï¼7 days, and the catheterization time was 14 days. Urinary continence occurred after catheter removal in 1 patient and was recovered 1 month later. CONCLUSIONS: RS-RARP is a safe, effective and reliable method for the treatment of prostate cancer and conducive to the early recovery of urinary continence.
Assuntos
Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Perda Sanguínea Cirúrgica , Humanos , Tempo de Internação , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Surgical treatment of carotid body tumors remains challenging, and this study evaluated the outcomes of carotid body tumor and pseudoaneurysm after blunt dissection of the tumors. METHODS: Six cases were classified as Shamblin groups I, II, and III (1, 1, and 4 cases, respectively). Tumor size ranged from 2 × 3 to 5 × 6 (median, 3.7 × 4.7) cm. Two patients underwent blunt dissection of the carotid body tumor, two underwent blunt dissection and ligation of the external carotid artery of the carotid body tumor, and two patients had common carotid artery-internal carotid artery artificial vascular reconstruction. RESULTS: No perioperative mortality or stroke occurred. The mean blood loss was 455 (range, 250-650) mL. Two patients had pseudoaneurysm or vocal cord paralysis postoperatively and recovered with stent graft implantation and medical treatment, respectively. The patients were followed for 6 to 17 (mean, 11) months, with no recurrence observed. CONCLUSION: Surgical treatment of a carotid body tumor is acceptably safe and effective according to Shamblin classification. Pseudoaneurysm can occur after blunt dissection of the tumor and can be treated with a stent graft.
Assuntos
Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/cirurgia , Tumor do Corpo Carotídeo/cirurgia , Dissecação/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Artérias Carótidas/cirurgia , Feminino , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC). METHODS: Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ(2) = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ(2) = 29.765, P = 0.000), Child-Pugh class (χ(2) = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ(2) = 43.086, P = 0.000), arterio-venous fistula (χ(2) = 29.791, P = 0.000), MWA therapy times (χ(2) = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ(2) = 28.660, P = 0.000) and targeted drug usage (χ(2) = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival. CONCLUSION: Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.
Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/mortalidade , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Veia Porta/patologia , Veia Porta/cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Trombose Venosa/etiologia , Trombose Venosa/mortalidade , Trombose Venosa/patologia , Trombose Venosa/terapia , Adulto JovemRESUMO
AIM: To compare conventional transarterial chemoembolization (c-TACE) with microsphere embolization in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and the Cochrane Library for trials assessing the efficacy and safety of c-TACE in comparison with those of yttrium-90 microsphere or drug-eluting bead embolization from January 2004 to December 2013. Overall survival rate (OSR), tumor response [complete response, partial response (PR), stable disease (SD), progressive disease (PD)], α-fetoprotein (AFP) response, progression rate and complications were compared and analyzed. Pooled ORs with 95%CI were calculated using either the fixed-effects model or random-effects model. All statistical analyses were conducted using the Review Manager (version 5.1.) from the Cochrane collaboration. RESULTS: Thirteen trials were identified, including a total of 1834 patients; 1233 were treated with c-TACE, 377 underwent yttrium-90 microsphere embolization and 224 underwent drug-eluting bead embolization. The meta-analysis with either the random-effects model or fixed-effects model indicated that microsphere embolization was associated with significantly higher OSRs compared with those of c-TACE (OR(1-year) = 1.38, 95%CI(1-year): 1.05-1.82; OR(2-year) = 2.88, 95%CI(2-year): 1.18-7.05; OR(3-year) = 2.15, 95%CI(3-year): 1.18-3.91). The complete tumor response rates of patients who underwent microspheres embolization were significantly higher than those of patients treated with c-TACE (OR = 2.19, 95%CI: 1.31-3.64). The tumor progression rate after microsphere embolization was markedly lower than that after c-TACE (OR = 0.56, 95%CI: 0.39-0.81). There was no significant difference between microsphere embolization and c-TACE in PR (OR = 0.73, 95%CI: 0.47-1.15), SD (OR = 1.07, 95%CI: 0.79-1.44), PD (OR = 0.75, 95%CI: 0.33-1.68), AFP response (OR = 1.38, 95%CI: 0.64-2.94) and complications (OR = 0.68, 95%CI: 0.46-1.00). CONCLUSION: Our analysis indicated that microsphere embolization was associated with superior survival and treatment response in comparison with c-TACE in the treatment of patients with HCC.