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1.
Oncologist ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907676

RESUMO

BACKGROUND: The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. METHODS: A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). RESULTS: Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). CONCLUSION: The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

2.
J Cancer Res Ther ; 20(2): 547-554, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687924

RESUMO

OBJECTIVE: To investigate the safety and short- and long-term efficacy of ultrasound-guided microwave ablation (MWA) with parallel acupuncture for treating single hepatocellular carcinoma (HCC) in high-risk areas. METHODS: Retrospective analysis was performed on 155 patients with single hepatocellular carcinoma who underwent microwave ablation in our hospital between December 2015 and September 2016. Patients with a tumor distance of ≤5 mm from the risk area were included in the observation group. Patients with a tumor distance of >5 mm from the risk area were placed in the control group. The patients' preoperative general health status, tumor site, tumor size, follow-up data, disease-free survival rate, overall survival rates, local tumor progression, and intrahepatic distant recurrence rate were collected and analyzed. RESULTS: The 1-, 3-, and 5-year overall survival rates for the observation group were 91.8%, 75.5%, and 59.2%, respectively. The 1-, 3-, and 5-year overall survival rates for the control group were 97.2%, 84.0%, and 66.0%, respectively. There were no significant differences between the two groups (P = 0.522). A tumor size of ≤20 mm (HR = 0.488, 95% CI = 0.254-0.940, P = 0.032) was an independent risk factor affecting the overall survival of patients with solitary HCC treated with MWA. The 1-, 3-, and 5-year recurrence-free survival rates for the observation group were 59.2%, 28.6%, and 18.4%, respectively, and those for the control group were 79.2%, 43.4%, and 31.1%, respectively. There was a statistical difference between the two groups (P = 0.007). Tumor size ≤20 mm (HR = 0.468, 95% CI = 0.303-0.723, P = 0.001), tumor location in a risk area (HR = 1.662, 95% CI = 1.121-2.465, P = 0.011), and an α-fetoprotein (AFP) level of <200 ug/L (HR = 0.612, 95% CI = 0.386-0.970, P = 0.036) are independent factors affecting the recurrence-free survival of MWA treatment for HCC. CONCLUSION: Microwave ablation with parallel acupuncture guided by ultrasound is a safe and effective treatment for single hepatocellular carcinoma in high-risk areas.


Assuntos
Terapia por Acupuntura , Carcinoma Hepatocelular , Neoplasias Hepáticas , Micro-Ondas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Idoso , Terapia por Acupuntura/métodos , Resultado do Tratamento , Taxa de Sobrevida , Recidiva Local de Neoplasia/patologia , Adulto , Seguimentos , Ultrassonografia de Intervenção/métodos
3.
Sci Rep ; 14(1): 6639, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503844

RESUMO

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics.


Assuntos
Neoplasias Hepáticas , Dor Visceral , Humanos , Butorfanol/uso terapêutico , Butorfanol/farmacologia , Dor Visceral/induzido quimicamente , Micro-Ondas/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Neoplasias Hepáticas/tratamento farmacológico
4.
Front Immunol ; 14: 1183871, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275887

RESUMO

Background: Idiopathic Pulmonary Fibrosis (IPF) can be described as a debilitating lung disease that is characterized by the complex interactions between various immune cell types and signaling pathways. Chromatin-modifying enzymes are significantly involved in regulating gene expression during immune cell development, yet their role in IPF is not well understood. Methods: In this study, differential gene expression analysis and chromatin-modifying enzyme-related gene data were conducted to identify hub genes, common pathways, immune cell infiltration, and potential drug targets for IPF. Additionally, a murine model was employed for investigating the expression levels of candidate hub genes and determining the infiltration of different immune cells in IPF. Results: We identified 33 differentially expressed genes associated with chromatin-modifying enzymes. Enrichment analyses of these genes demonstrated a strong association with histone lysine demethylation, Sin3-type complexes, and protein demethylase activity. Protein-protein interaction network analysis further highlighted six hub genes, specifically KDM6B, KDM5A, SETD7, SUZ12, HDAC2, and CHD4. Notably, KDM6B expression was significantly increased in the lungs of bleomycin-induced pulmonary fibrosis mice, showing a positive correlation with fibronectin and α-SMA, two essential indicators of pulmonary fibrosis. Moreover, we established a diagnostic model for IPF focusing on KDM6B and we also identified 10 potential therapeutic drugs targeting KDM6B for IPF treatment. Conclusion: Our findings suggest that molecules related to chromatin-modifying enzymes, primarily KDM6B, play a critical role in the pathogenesis and progression of IPF.


Assuntos
Fibrose Pulmonar Idiopática , Camundongos , Animais , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/patologia , Bleomicina , Cromatina , Biologia Computacional , Histona Desmetilases com o Domínio Jumonji/genética , Histona-Lisina N-Metiltransferase/genética
5.
World J Surg Oncol ; 21(1): 42, 2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36765340

RESUMO

BACKGROUND: Hepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC. METHODS: Data on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group) and did not receive it (non-AVT group). Logistic regression was used to identify the independent factors for viral reactivation. The tumor recurrence and overall survival (OS) rates were analyzed using the Kaplan-Meier method. Recurrence patterns were also investigated. RESULTS: HBV reactivation developed in 10.8% (58/538) of patients after PRFA. AVT was associated independently with decreased viral reactivation (odd ratio: 0.061, 95% confidence interval: 0.018-0.200). In 215 pairs of patients obtained after PSM, the AVT group had lower 1-, 3-, and 5-year recurrence rates (24%, 55%, and 67% vs 33%, 75%, and 85%, respectively) and higher 1-, 3-, and 5-year OS rates (100%, 67%, and 59% vs 100%, 52%, and 42%, respectively) than non-AVT group (P < 0.001 for both). Additionally, the relapses in distant hepatic segments and the late recurrence after 2 years of PRFA were significantly reduced in the AVT group (78/215 vs 111/215 vs., P = 0.001; 39/109 vs. 61/91, P = 0.012, respectively). CONCLUSIONS: AVT reduced late and distal intrahepatic recurrence and improved OS in patients undergoing PRFA for HBV-related HCC by inhibiting viral reactivation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/patologia , Vírus da Hepatite B/genética , Neoplasias Hepáticas/patologia , Hepatectomia/efeitos adversos , Recidiva Local de Neoplasia/cirurgia , Antivirais/uso terapêutico , DNA Viral , Estudos Retrospectivos
6.
Front Oncol ; 12: 1020898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561516

RESUMO

Purpose: This study aimed to identify independent prognosis-associated factors of bone-metastatic prostate cancer. The nomograms were further developed to obtain indicators for the prognostic evaluation. Methods: A total of 7315 bone-metastatic prostate cancer (PCa) patients from 2010 to 2016 were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n=5,120) and test cohort (n=2,195) in a ratio of 7:3. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors. A 1:1 propensity score matching (PSM) was further performed to decrease the confounding effect and re-evaluate the influence of radical prostatectomy and chemotherapy on prognosis. Combining these potential prognosis factors, the nomograms of cancer-specific survival (CSS) and overall survival (OS) at different times were established. C-indexes, calibration curves, and decision curves were developed to evaluate the discrimination, calibration, and clinical benefit of the nomograms. Results: Eleven independent prognosis factors for CSS and twelve for OS were utilized to conduct the nomograms respectively. The C-indexes of nomograms for CSS and OS were 0.712 and 0.702, respectively. A favorable consistency between the predicted and actual survival probabilities was demonstrated by adopting calibration curves. Decision curves also exhibited a positive clinical benefit of the nomograms. Conclusions: Nomograms were formulated successfully to predict 3-year and 5-year CSS and OS for bone-metastatic PCa patients. Radical prostatectomy and chemotherapy were strongly associated with the bone-metastatic PCa prognosis.

7.
Front Immunol ; 13: 988479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211429

RESUMO

Background: The coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma. Methods: Two sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury. Results: We discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein-protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor-gene interactions, DEG-microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes. Conclusion: We identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.


Assuntos
Asma , COVID-19 , MicroRNAs , Animais , Asma/genética , Biomarcadores Tumorais/genética , COVID-19/genética , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Interleucina-13/genética , Interleucina-5/genética , Camundongos , MicroRNAs/genética , Biologia de Sistemas , Fatores de Transcrição/genética
8.
Int J Surg ; 105: 106843, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35995351

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) are two commonly used biomarkers for detection and prognostic prediction of hepatocellular carcinoma (HCC). This study sought to evaluate and compare the use of these two biomarkers to detect HCC, as well as predict postoperative early recurrence (within 2 years after HCC resection). METHODS: Data on consecutive patients who underwent curative resection for HCC between 2014 and 2020 was prospectively collected and reviewed. Serum AFP and PIVKA-II levels within one week before surgery or at the time of detection of early recurrence were assessed; preoperative AFP positivity (≥20 ng/ml) and preoperative PIVKA-II positivity (≥40 mAU/ml) were examined relative to recurrence using univariate and multivariate Cox-regression analyses. RESULTS: Among 751 patients who underwent curative HCC resection, 589 (78.4%) patients had preoperative PIVKA-II positivity versus 498 (66.3%) patients had preoperative AFP positivity (P < 0.001). With a median follow-up of 41.6 months, 370 (50.1%) patients had an early HCC recurrence; among patients with an early recurrence, the proportion of patients with PIVKA-II positivity versus AFP positivity (76.5% vs. 60.0%, P = 0.002) was higher. On multivariate analysis, preoperative PIVKA-II positivity, but not preoperative AFP positivity was an independent risk factor to predict early recurrence after HCC resection. CONCLUSIONS: AFP and PIVKA-II are useful biomarkers to detect resectable HCC and predict early recurrence after HCC resection, with the latter showing higher rates of positivity. Preoperative PIVKA-II positivity was independently associated with early recurrence following HCC resection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Precursores de Proteínas , Protrombina , Curva ROC , Estudos Retrospectivos , Vitamina K , alfa-Fetoproteínas/análise
9.
J Cancer Res Ther ; 18(2): 329-335, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35645097

RESUMO

Purpose: To compare the therapeutic efficacy and safety of percutaneous microwave ablation (MWA) with those of percutaneous radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) adjacent to major vessels. Methods: From January 2010 to April 2011, 78 patients with a single nodule, no >5 cm, adjacent to major vessels were enrolled in this study. Forty-four patients (forty-one men, three women; age range, 33-72 years) treated by MWA were compared with thirty-four patients (thirty-one men, three women; age range, 33-75 years) treated by RFA. Local tumor progression rate, overall survival rate, and disease-free survival rate were calculated using the Kaplan-Meier method, and differences between groups were estimated by log-rank test. Results: No death related to treatment occurred in the two groups. The 1-, 2-, and 3-year local tumor progression rates were 6.8%, 11.4%, and 15.9%, respectively, in the microwave group versus 17.6%, 20.6%, and 20.6%, respectively in the radiofrequency group (P = 0.544). The rates of major complications associated with microwave and RFA were 2.3% (1/44) versus 0% (0/34; P = 0.376). The microwave group's 1-, 2-, and 3-year disease-free survival rates were 72.7%, 65.9%, and 51.8%, respectively, and those in the radiofrequency were 58.8%, 52.9%, and 47.1%, respectively (P = 0.471). The microwave group's 1-, 2-, and 3-year overall survival rates were 93.2%, 90.9%, and 83.6%, respectively, and those in the radiofrequency group were 91.2%, 88.2%, and 82.4%, respectively (P = 0.808) There was no significant difference in local tumor progression, complications related to treatment, and long-term results between the two modalities. The incidence of peritumoral structure damage on image scan was significantly higher in the microwave group than in the RFA group (P = 0.025). Conclusions: Both RFA and MWA are safe and effective techniques for HCC adjacent to major vessels and have the same clinical value.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablação por Radiofrequência , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Resultado do Tratamento
10.
Ann Surg Oncol ; 28(13): 8174-8185, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34409542

RESUMO

OBJECTIVES: The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) based on preoperative predicted microvascular invasion (MVI) risk. METHODS: Data on consecutive patients who underwent LR (n = 1344) or PRFA (n = 853) for hepatitis B virus-related HCC within the Milan criteria (MC) were analyzed. A preoperative nomogram was used to estimate MVI risk. Overall survival (OS), time to recurrence, and patterns of recurrence were compared using propensity score matching. RESULTS: The concordance indices of the nomogram to predict MVI were 0.813 and 0.781 among LR patients with HCC within the MC or ≤ 3 cm, respectively. LR and PRFA resulted in similar 5-year recurrence and OS for patients with nomogram-predicted low-risk of MVI. LR provided better 5-year recurrence and OS versus PRFA for patients with high-risk of MVI (71.6% vs. 80.7%, p = 0.013; 47.9% vs. 34.0%, p = 0.002, for HCC within the MC; 62.3% vs. 78.8%, p = 0.020; 63.6% vs. 38.3%, p = 0.015, for HCC ≤ 3 cm). Among high-risk patients, LR was associated with lower recurrence and improved OS compared with PRFA, on multivariate analysis [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63-0.97, and HR 0.68, 95% CI 0.52-0.88, for HCC within the MC; HR 0.51, 95% CI 0.32-0.81, and HR 0.47, 95% CI 0.26-0.84, for HCC ≤ 3 cm], and resulted in less early and local recurrence than PRFA (42.4% vs. 54.8%, p = 0.007, and 31.2% vs. 46.1%, p = 0.007, for HCC within the MC; 27.9% vs. 50.8%, p = 0.016, and 15.6% vs. 39.5%, p = 0.046, for HCC ≤ 3 cm). CONCLUSIONS: LR was oncologically superior over PRFA for early HCC patients with predicted high-risk of MVI. LR was associated with better local disease control than PRFA in these patients.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/cirurgia , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos
12.
JAMA Oncol ; 6(2): 255-263, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774468

RESUMO

Importance: Repeat hepatectomy and percutaneous radiofrequency ablation (PRFA) are most commonly used to treat early-stage recurrent hepatocellular carcinoma (RHCC) after initial resection, but previous studies comparing the effectiveness of the 2 treatments have reported conflicting results. Objective: To compare the long-term survival outcomes after repeat hepatectomy with those after PRFA among patients with early-stage RHCC. Design, Setting, and Participants: This open-label randomized clinical trial was conducted at the Eastern Hepatobiliary Surgery Hospital and the National Center for Liver Cancer of China. A total of 240 patients with RHCC (with a solitary nodule diameter of ≤5 cm; 3 or fewer nodules, each ≤3 cm in diameter; and no macroscopic vascular invasion or distant metastasis) were randomized 1:1 to receive repeat hepatectomy or PRFA between June 3, 2010, and January 15, 2013. The median (range) follow-up time was 44.3 (4.3-90.6) months (last follow-up, January 15, 2018). Data analysis was conducted from June 15, 2018, to September 28, 2018. Interventions: Repeat hepatectomy (n = 120) or PRFA (n = 120). Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary outcomes included repeat recurrence-free survival (rRFS), patterns of repeat recurrence, and therapeutic safety. Results: Among the 240 randomized patients (216 men [90.0%]; median [range] age, 53.0 [24.0-59.0] years), 217 completed the trial. In the intention-to-treat (ITT) population, the 1-year, 3-year, and 5-year OS rates were 92.5% (95% CI, 87.9%-97.3%), 65.8% (95% CI, 57.8%-74.8%), and 43.6% (95% CI, 35.5%-53.5%), respectively, for the repeat hepatectomy group and 87.5% (95% CI, 81.8%-93.6%), 52.5% (95% CI, 44.2%-62.2%), and 38.5% (95% CI, 30.6%-48.4%), respectively, for the PRFA group (P = .17). The corresponding 1-year, 3-year, and 5-year rRFS rates were 85.0% (95% CI, 78.8%-91.6%), 52.4% (95% CI, 44.2%-62.2%), and 36.2% (95% CI, 28.5%-46.0%), respectively, for the repeat hepatectomy group and 74.2% (95% CI, 66.7%-82.4%), 41.7% (95% CI, 33.7%-51.5%), and 30.2% (95% CI, 22.9%-39.8%), respectively, for the PRFA group (P = .09). Percutaneous radiofrequency ablation was associated with a higher incidence of local repeat recurrence (37.8% vs 21.7%, P = .04) and early repeat recurrence than repeat hepatectomy (40.3% vs 23.3%, P = .04). In subgroup analyses, PRFA was associated with worse OS vs repeat hepatectomy among patients with an RHCC nodule diameter greater than 3 cm (hazard ratio, 1.72; 95% CI, 1.05-2.84) or an α fetoprotein level greater than 200 ng/mL (hazard ratio, 1.85; 95% CI, 1.15-2.96). Surgery had a higher complication rate than did ablation (22.4% vs 7.3%, P = .001). Conclusions and Relevance: No statistically significant difference was observed in survival outcomes after repeat hepatectomy vs PRFA for patients with early-stage RHCC. Repeat hepatectomy may be associated with better local disease control and long-term survival in patients with an RHCC diameter greater than 3 cm or an AFP level greater than 200 ng/mL. Trial Registration: ClinicalTrials.gov identifier: NCT00822562.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Ablação por Radiofrequência , Reoperação , Adulto , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Adulto Jovem
13.
Radiology ; 292(1): 237-247, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31135299

RESUMO

Background The evidence of combining sorafenib with transarterial chemoembolization (TACE) for intermediate-stage recurrent hepatocellular carcinoma (HCC) is limited. Patient responses to this treatment varied because of the heterogeneous nature of intermediate-stage recurrent HCC, making it important to identify patients who are most likely to benefit from this combination therapy. Purpose To compare sorafenib administered in combination with TACE versus TACE alone in the treatment of recurrent intermediate-stage HCC after initial hepatectomy and to determine the relationship of microvascular invasion (MVI) to survival. Materials and Methods In this retrospective multicenter study, 3652 consecutive patients were found to have intrahepatic recurrences after initial hepatectomy of primary HCC from January 2010 to December 2016. Of these, 260 patients with intermediate-stage recurrent HCC underwent combination treatment with sorafenib and TACE or TACE alone. Overall survival (OS) and progression-free survival (PFS) were compared between these two treatments according to MVI status by using log-rank tests. Results A total of 128 patients were administered combination therapy (mean age, 55 years ± 7.6 [standard deviation]; 107 men) and 132 patients were administered TACE alone (mean age, 56 years ± 8.3; 110 men). The 5-year OS and PFS were higher in the combination group than in the TACE group (OS: 38.9% vs 20.5%, respectively, P = .01; PFS, 37.5% vs 18.7%, respectively, P = .003). For patients with MVI-positive lesions, the median OS and PFS after combination treatment (n = 55) were longer than those after TACE alone (n = 72; OS: 17.2 months vs 12.1 months, respectively, P = .02; PFS: 17.0 months vs 11.0 months, respectively, P = .02). Multivariable analysis showed that tumor number, MVI status, and treatment allocation were significant predictors of OS and PFS, whereas tumor size was a prognostic factor for PFS. Conclusion Patients with recurrent intermediate-stage hepatocellular carcinoma and lesions positive for microvascular invasion (MVI) had longer survival times by using a combined treatment of sorafenib with transarterial chemoembolization (TACE) compared with TACE alone; patients with MVI-negative lesions did not show survival benefit from combined therapy. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Malloy in this issue.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Microvasos/patologia , Recidiva Local de Neoplasia/terapia , Sorafenibe/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Terapia Combinada , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/irrigação sanguínea , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Resultado do Tratamento
14.
J Exp Med ; 215(9): 2397-2412, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30021797

RESUMO

Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Numerous studies have suggested that early life exposure to lipopolysaccharide (LPS) is negatively associated with allergic asthma. One proposed mechanism invokes desensitization of lung epithelial cells by LPS. We report here that acyloxyacyl hydrolase (AOAH), a host lipase that degrades and inactivates LPS, renders mice more susceptible to house dust mite (HDM)-induced allergic asthma. Lung epithelial cells from Aoah-/- mice are refractory to HDM stimulation, decreasing dendritic cell activation and Th2 responses. Antibiotic treatment that diminished commensal LPS-producing bacteria normalized Aoah-/- responses to HDM, while giving LPS intrarectally ameliorated asthma. Aoah-/- mouse feces, plasma, and lungs contained more bioactive LPS than did those of Aoah+/+ mice. By inactivating commensal LPS, AOAH thus prevents desensitization of lung epithelial cells. An enzyme that prevents severe lung inflammation/injury in Gram-negative bacterial pneumonia has the seemingly paradoxical effect of predisposing to a Th2-mediated airway disease.


Assuntos
Asma/imunologia , Hidrolases de Éster Carboxílico/imunologia , Células Dendríticas/imunologia , Células Epiteliais/imunologia , Lipase/imunologia , Lipopolissacarídeos/toxicidade , Pulmão/imunologia , Animais , Asma/genética , Asma/patologia , Hidrolases de Éster Carboxílico/genética , Células Dendríticas/patologia , Modelos Animais de Doenças , Células Epiteliais/patologia , Lipase/genética , Lipopolissacarídeos/imunologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Células Th2/imunologia , Células Th2/patologia
15.
Eur Radiol ; 28(9): 3651-3660, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29600474

RESUMO

OBJECTIVES: To compare combined percutaneous radiofrequency ablation and ethanol injection (RFA-PEI) with hepatic resection (HR) in the treatment of resectable solitary hepatocellular carcinoma (HCC) with 2.1-5.0 cm diameter. METHODS: From June 2009 to December 2015, 271 patients whom underwent RFA-PEI (n = 141) or HR (n = 130) in three centres were enrolled. The overall survival (OS) and recurrence-free survival (RFS) between groups were compared with Kaplan-Meier method and log-rank tests. Complications, hospital stay and cost were assessed. RESULTS: The OS rates at 1, 3 and 5 years were 93.5%, 72.7%, 58.6% in RFA-PEI group and 82.3%, 57.5%, 51.8% in HR group (p = 0.021). The corresponding 1-, 3- and 5-year RFS rates were 65.8%, 41.3%, 34.3% in RFA-PEI group and 50.5%, 33.8%, 28.4% in HR group (p = 0.038). For patients with 2.1-3.0 cm tumours, the 1-, 3- and 5-year OS after RFA-PEI and HR were 98.0%, 82.3%, 74.2% and 89.4%, 65.1%, 61.9%, respectively (p = 0.024). The corresponding RFS were 79.6%, 54.7%, 45.1% in RFA-PEI group, and 57.6%, 43.9%, 31.7% in HR group, respectively (p = 0.020). RFA-PEI was superior to HR in major complication rates, length of hospital stay and cost (all p < 0.001). CONCLUSION: RFA-PEI had a survival benefit over HR in the treatment of solitary HCCs, especially for those with 2.1-3.0 cm in diameter. KEY POINTS: • RFA-PEI provided superior survival to HR in solitary HCC with 2.1-5.0 cm in diameter. • RFA-PEI is superior to HR in complications, length of hospital stay and cost. • RFA-PEI might be an alternative treatment for solitary HCC within 5.0 cm in diameter.


Assuntos
Carcinoma Hepatocelular/terapia , Ablação por Cateter/métodos , Etanol/administração & dosagem , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/secundário , Terapia Combinada , Feminino , Humanos , Injeções Intralesionais , Tempo de Internação/estatística & dados numéricos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
Radiology ; 287(2): 705-714, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29390197

RESUMO

Purpose To retrospectively investigate the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) in the treatment of recurrent hepatocellular carcinoma (rHCC) with portal vein tumor thrombosis, extrahepatic metastases (advanced hepatocellular carcinoma), or both after initial hepatectomy. Materials and Methods The study was centrally approved by the ethics committee of three tertiary medical centers in China. From January 2010 to January 2015, 207 consecutive patients with advanced rHCC after initial hepatectomy received sorafenib combined with TACE-RFA (combination group, n = 106) or sorafenib alone (sorafenib group, n = 101) at the three medical centers. Overall survival (OS) and time to progression (TTP) were compared between the two groups. Complications were assessed. Survival curves were constructed with the Kaplan-Meier method and were compared with the log-rank test. Results Baseline characteristics were balanced between the two groups. No treatment-related death occurred in either group. The toxicity profile in the combination group was similar to that in the sorafenib group. After treatment, median OS (14.0 vs 9.0 months, respectively; P < .001) and TTP (7.0 vs 4.0 months, respectively; P < .001) were significantly longer in the combination group than in the sorafenib group. Multivariate analysis showed that treatment allocation was a significant predictor of OS and TTP, while the number of intrahepatic tumors was another prognostic factor of OS. Conclusion Sorafenib combined with TACE-RFA was well tolerated and safe and was superior to sorafenib alone in improving survival outcomes in patients with advanced rHCC after initial hepatectomy. © RSNA, 2018 Online supplemental material is available for this article.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Ablação por Cateter , Quimioembolização Terapêutica , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/prevenção & controle , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Eur Radiol ; 27(9): 3877-3887, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28188425

RESUMO

OBJECTIVES: This study aimed to evaluate the feasibility, local efficacy and long-term outcomes of microwave (MW) ablation for the treatment of hepatocellular carcinoma (HCC) that met up-to-seven criteria. METHODS: Between January 2007 and January 2012, 142 HCC patients with 294 nodules, which conformed to up-to-seven criteria, were enrolled into this retrospective study. All patients were followed up for more than 3 years after receiving MW ablation. Technical success, complications, local tumour progression (LTP) and distant recurrence (DR) were monitored. Recurrence-free survival (RFS), overall survival (OS) and prognostic factors were analysed. RESULTS: Primary technical efficacy was achieved in 95.2% (280/294) of the carcinomatous nodules, and major complications occurred in four (2.8%) patients. Among the 294 tumours, LTP was observed in 44 (15.0%) tumours. Among the 142 patients, DR was observed in 97 (68.3%) patients. The estimated OS rates after MW ablation at 1, 3 and 5 years were 97.2%, 75.4% and 50.6%, respectively; and the corresponding RFS rates were 76.1%, 33.1% and 19.5%, respectively. CONCLUSIONS: MW ablation is a safe and effective treatment with a high rate of primary technical efficacy for patients with HCC that met up-to-seven criteria. KEY POINTS: • The first study expanding MW ablation to HCC category beyond Milan criteria. • The first report that used up-to-seven criteria as indications for MW ablation. • HCC of up-to-seven criteria viewed as a subgroup of BCLC stage B. • MW ablation is safe and effective for treating HCC within up-to-seven criteria. • MW ablation is preferable in treating unresectable HCC within up-to-seven criteria.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Chin J Cancer ; 36(1): 14, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-28103953

RESUMO

BACKGROUND: Percutaneous radiofrequency ablation (RFA) is a first-line treatment for very-early-stage hepatocellular carcinoma (HCC), whereas the efficacy of percutaneous microwave ablation (MWA) for very-early-stage HCC remains unclear. The purpose of this study was to clarify this issue by comparing the safety and efficacy of percutaneous MWA with percutaneous RFA in treating very-early-stage HCC. METHODS: Clinical data of 460 patients who were diagnosed with very-early-stage HCC and treated with percutaneous MWA or RFA between January 2007 and July 2012 at the Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, in Shanghai, China were retrospectively analyzed. Of these 460 patients, 159 received RFA, 301 received MWA. Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), complete ablation, and complication occurrence rates were compared between the two groups, and the prognostic factors associated with survival were analyzed. RESULTS: No significant differences were observed between the two groups in terms of the 1-, 3-, or 5-year OS rates (99.3%, 90.4%, and 78.3% for MWA vs. 98.7%, 86.8%, and 73.3% for RFA, respectively; P = 0.331). Furthermore, no significant differences were observed between the two groups in terms of the corresponding RFS rates (94.4%, 71.8%, and 46.9% for MWA vs. 89.9%, 67.3%, and 54.9% for RFA, respectively; P = 0.309), the LTP rates (9.6% vs. 10.1%, P = 0.883), the complete ablation rates (98.3% vs. 98.1%, P = 0.860), or the occurrence rates of major complications (0.7% vs. 0.6%, P = 0.691). By multivariate analysis, LTP, antiviral therapy, and treatment of recurrence were independent risk factors for OS (P < 0.001), and the alpha-fetoprotein level was an independent prognostic factor for RFS (P = 0.002). CONCLUSIONS: MWA is as safe and effective as RFA in treating very-early-stage HCC, supporting MWA as a first-line treatment option for this disease.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Micro-Ondas , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
Int J Hyperthermia ; 33(3): 247-254, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27649577

RESUMO

OBJECTIVE: This study aims to evaluate the local efficacy and long-term outcomes of microwave ablation (MWA) for treating large unresectable hepatocellular carcinomas (HCCs). METHODS: A total of 82 patients with 5-6 cm unresectable HCCs, who underwent a single MWA procedure during the period of January 2007 to July 2011, were retrospectively enrolled into this study. Percentages of technical success and complications of MWA and HCC local recurrence (LR) after MWA were determined. In addition, prognostic factors were screened and overall survival (OS) and recurrence-free survival (RFS) rates were estimated. RESULTS: One-, three- and five-year OS rates in this MWA-treated cohort were 92.7, 63.4 and 41.1%, respectively; and the corresponding RFS rates were 65.9, 31.7 and 23.0%, respectively. Primary technical efficacy was 89.0% after the first round of ablation, three (3.7%) patients developed major complications, and LR rate was 20.7%. Child-Pugh classification (p < .001), tumour location (p = .049) and LR (p = .002) were independent factors associated with OS, as determined by multivariate analysis. CONCLUSIONS: MWA is safe and effective for the treatment of selected large HCCs, and provides an alternative treatment option for patients with unresectable HCCs. Furthermore, the favourable local efficacy of MWA could potentially improve long-term survival.

20.
Oncotarget ; 7(26): 40816-40829, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27027235

RESUMO

Hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT) is associated with poor prognosis, early recurrence of HCC, and limited treatment options. Current guidelines do not have standardized diagnostic and treatment modalities, thus creating a need for a multidisciplinary treatment model for standardization of the treatment. Eastern Hepatobiliary Surgical Hospital (China) convened two working parties of experts from all the departments, to consolidate the current evidence, prevailing vision for the future, and experience of the practicing clinicians engaged in HCC management, so as to develop a consensus for PVTT diagnosis and treatment according to the GRADE system. Based on the quality of the existing evidence and the strength of recommendations, the consensus statements were categorized into 3 evidence levels (A/B/C) and 5 classes (I/II/IIa/IIb/III).The panel discussed and provided clarity on the management and research options in the field of HCC with PVTT. In addition, the panel also assessed the quality of the cited studies and assigned grades to the recommendation statements. Among the group of experts, there was excellent agreement with regard to effective diagnosis and treatment of HCC with PVTT. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective management of HCC with PVTT.


Assuntos
Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/complicações , Administração Oral , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , China , Hepatectomia , Humanos , Imunoterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Oncologia/métodos , Oncologia/normas , Microcirculação , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia , Veia Porta/patologia , Prognóstico , Radioterapia/métodos , Trombose/complicações , Trombose/patologia , Resultado do Tratamento
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