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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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Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Tempo Operativo , Próstata/cirugía , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
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 , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Microondas/uso terapéutico , Estadificación de Neoplasias/métodos , Nomogramas , Terapia por Radiofrecuencia/métodos , Adolescente , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
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 Ablación , Bilirrubina/sangre , Plaquetas , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Microondas/uso terapéutico , Albúmina Sérica/análisis , Índice de Severidad de la Enfermedad , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
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.
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Laparoscopía/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos Robotizados , Pérdida de Sangre Quirúrgica , Humanos , Tiempo de Internación , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Tempo Operativo , Periodo Posoperatorio , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
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.
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Traumatismos de las Arterias Carótidas/etiología , Traumatismos de las Arterias Carótidas/cirugía , Tumor del Cuerpo Carotídeo/cirugía , Disección/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Anciano , Arterias Carótidas/cirugía , Femenino , Humanos , Ligadura , Masculino , Persona de Mediana Edad , Reoperación , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/AIMS: To evaluate the curative effect and clinical application of hepatic arterial infusion (HAI) chemotherapy combined with endogenetic field tumor hyperthermia (EFTH) in patients with hilar cholangiocarcinoma. METHODOLOGY: Nine patients with unresectable hilar cholangiocarcinoma were enrolled. They were first treated with HAI using gemcitabine, and then carboplatin was continuously infused intra-arterially whereas EFTH was applied to the hilar region for 60 min. After hyperthermia, 5-fluorouracil was administered intra-arterially for three days. The same dose of gemcitabine was administered intravenously on Day 8. The side effects, tumor markers, tumor response and overall survival (OS) were observed and assessed. RESULTS: Nine patients underwent 27 cycles of the combination therapy. Of the nine patients, five patients achieved complete remission and they are still alive, and four died. Of the four patients who died, two achieved partial remission, one had stable disease, and one had progressive disease. The tumor markers decreased at varied degrees among the seven patients. The overall response rate was 77.78% (7/9), and the disease control rate was 88.89% (8/9). The treatment had no severe side effects and complications, including grade 3/4 hematological toxicities. CONCLUSIONS: HAI chemotherapy combined with EFTH is safe, minimally invasive, and well tolerated.
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Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/terapia , Arteria Hepática , Hipotermia Inducida/métodos , Anciano , Biomarcadores de Tumor/análisis , Carboplatino/uso terapéutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Diagnóstico por Imagen , Femenino , Fluorouracilo/uso terapéutico , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
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/patología , Neoplasias Hepáticas/patología , Resultado del Tratamiento , Arteria Hepática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéutico , Infusiones IntraarterialesRESUMEN
BACKGROUND AND AIM: To evaluate the clinical benefits of transarterial chemoembolization (TACE) monotherapy or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of patients with large primary hepatocellular carcinoma (HCC) treated with these techniques. METHODS: This is a retrospective study involving 136 patients with unresectable large HCC (189 tumor nodules, ≥ 5.0 cm in diameter) admitted to Sun Yat-Sen University Memorial Hospital (Guangzhou, China) between January 2004 and December 2011. The median follow-up time was 41 months (range, 6-96 months). Of these patients, 80 patients received TACE monotherapy and 56 patients received TACE combined with PMCT. The median interval between treatments and overall survival (OS) were hierarchically analyzed using log-rank tests. RESULTS: All patients successfully underwent TACE alone or TACE with PMCT with no serious complications. The median survival time was 13 months (range, 3-84 months) for the TACE group and 25 months (range, 7-96 months) for the TACE-PMCT group. The 1-year, 3-year, and 5-year OS rates were 62.5%, 17.5%, and 5.0% in the TACE group, respectively. In contrast, in the TACE-PMCT group, the 1-year, 3-year, and 5-year OS rates were 87.5%, 50.0%, and 10.0%, respectively. This difference was statistically significant between the groups (P < 0.001). CONCLUSIONS: TACE combined with PMCT had advantages in prolonging OS with satisfying time to progression and improving liver function in patients with large unresectable HCC. The results suggest that further prospective studies are required to confirm the findings of this study.
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Técnicas de Ablación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Técnicas de Ablación/métodos , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Radiografía Intervencional , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
OBJECTIVE: To investigate the safety and clinical efficacy of uterime artery chemoembolization in postpartum hemorrhage (PPH) caused by abnormal placental implantation. METHODS: Between December 2006 and September 2009, there were 23 cases of abnormal placental implantation with PPH in our hospital, among which 9 presented with continuous small amount of vaginal bleeding and 14 with acute excessive bleeding. The average bleeding time was (8+/-6) d and the mean blood loss was (980+/-660) ml. Abnormal placental implantation was confirmed by color Doppler ultrasound (CD-US) in all cases, the internal iliac artery angiography was performed to identify the uterine artery and bilateral uterine artery chemoembolization (UACE) with methotrexate (MTX) and gelfoam particles to the distal end of uterine artery was conducted after. CD-US rechecked all patients within 48 h after UACE and those patients with blurred margins between placenta and uterus and abnormal blood flow (>1 cmx1 cm) received ultrasonic-guided per vagina MTX multipoint injections. All cases were followed up for 3-26 months (average 12 months) to observe vaginal bleeding, placenta tissue discharge, serum human chorionic gonadotropin (hCG), uterine involution, menses, and side-effects or complications. RESULTS: (1) Curative effect: These 23 cases underwent 24 procedures of UACE successfully and vaginal bleeding ceased at an average of (3.5+/-1.3) min after UACE. Reduced blood flow in the placental implantation area was detected under CD-US after UACE. Among the 23 patients, wterine curettage was required in 16 cases due to retained placenta tissues with the mean blood loss of (40+/-28) ml during the operation, 2 underwent subtotal hysterectomy and confirmed to be placenta percreta by pathology examination, and placenta tissues were spontaneously discharged completely in 5 cases. Totally, 91% of the patients (21/23) reserved their uterus. (2) FOLLOW-UP: the serum hCG reduced to normal within 1-13 d after the placenta tissue were evacuated. Regular menstruation returned within 2-3 months in those patients who reserved uterus and normal size uterus was found under sonography at 3 months. No severe complication was reported except for some post embolization syndrome, such as pelvic pain or fever. CONCLUSIONS: UACE, combined with ultrasonic-guided transvaginal MTX injection, is a safe, minimal invasive and quick hemostatic procedure in treatment of abnormal placental implantation with PPH, and allows the preservation of uterus possible. CD-US is helpful in evaluation of the blood flow changes before and after UACE in abnormal placental implantation patients.
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Quimioembolización Terapéutica/métodos , Metotrexato/administración & dosificación , Placenta Accreta/terapia , Hemorragia Posparto/terapia , Adulto , Gonadotropina Coriónica/sangre , Femenino , Estudios de Seguimiento , Humanos , Placenta Accreta/diagnóstico por imagen , Hemorragia Posparto/etiología , Embarazo , Resultado del Tratamiento , Ultrasonografía Doppler en Color , Arteria Uterina , Útero/irrigación sanguínea , Útero/diagnóstico por imagen , Vagina/diagnóstico por imagen , Adulto JovenRESUMEN
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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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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Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Quinasa 2 Dependiente de la Ciclina/genética , Amplificación de Genes , N-Metiltransferasa de Histona-Lisina/genética , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/genética , Animales , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/secundario , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Progresión de la Enfermedad , Femenino , Amplificación de Genes/fisiología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Activación Transcripcional , Células Tumorales Cultivadas , Regulación hacia Arriba/genéticaRESUMEN
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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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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Infecciones Bacterianas/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Adulto , Biomarcadores/sangre , Citocinas/sangre , Dimerización , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Voluntarios Sanos , Humanos , Regiones Constantes de Inmunoglobulina/genética , Mediadores de Inflamación/sangre , Infusiones Intravenosas , Reacción en el Punto de Inyección/etiología , Interleucinas/genética , Masculino , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/farmacocinética , Proteína Amiloide A Sérica/metabolismo , Adulto Joven , Interleucina-22RESUMEN
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/cirugía , Ablación por Catéter/métodos , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/cirugía , Ablación por Radiofrecuencia/métodos , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Tiempo de Internación , Neoplasias Hepáticas/patología , Masculino , Oportunidad Relativa , Tasa de Supervivencia , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
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.
RESUMEN
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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Quimioembolización Terapéutica/métodos , Sarcoma/terapia , Adulto , Quimioembolización Terapéutica/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sarcoma/irrigación sanguínea , Tasa de SupervivenciaRESUMEN
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.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Sorafenib/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/secundario , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Vena Porta/patología , Pronóstico , Modelos de Riesgos Proporcionales , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Carga Tumoral , Adulto JovenRESUMEN
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.