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1.
J Transl Med ; 20(1): 492, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36309694

RESUMO

BACKGROUND: N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. METHODS: Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan-Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. RESULTS: Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan-Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. CONCLUSIONS: An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética
2.
Bioorg Chem ; 119: 105534, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34894576

RESUMO

Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2-11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15-50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Células Matadoras Naturais/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
3.
Genomics ; 113(2): 740-754, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33516849

RESUMO

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.


Assuntos
Autofagia/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Longo não Codificante/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , RNA Longo não Codificante/metabolismo
4.
HPB (Oxford) ; 24(4): 547-557, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34635434

RESUMO

BACKGROUND: Surgical resection is the primary treatment for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT). This study was conducted to investigate the efficacy of postoperative adjuvant TACE (PA-TACE) in patients with HCC and BDTT. METHODS: Data from patients who underwent surgery for HCC with BDTT at two medical centers were retrospectively analyzed. The survival outcomes of patients who were treated by hepatic resection followed by PA-TACE were compared with those of patients who underwent surgery alone. Propensity score matching (PSM) analysis was performed with a 1:1 ratio. RESULTS: Of the 308 consecutively enrolled HCC patients with BDTT who underwent surgical resection, 134 underwent PA-TACE whereas 174 underwent surgery alone. From the initial cohort, PSM matched 106 pairs of patients. The OS and DFS rates were significantly better for the PA-TACE group than the surgery alone group (for OS: before PSM, P = 0.026; after PSM, P = 0.039; for DFS: before PSM, P = 0.010; after PSM, P = 0.013). CONCLUSION: PA-TACE was associated with better survival outcomes than surgery alone for patients with HCC and BDTT. Prospective clinical trials are warranted to validate the beneficial effect of PA-TACE on HCC patients associated with BDTT.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Trombose , Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Prognóstico , Pontuação de Propensão , Estudos Prospectivos , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/terapia
5.
HPB (Oxford) ; 24(7): 1063-1073, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34961677

RESUMO

BACKGROUND: Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. METHODS: A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. RESULTS: Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. CONCLUSION: Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatectomia/efeitos adversos , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 409-413, 2022 May.
Artigo em Zh | MEDLINE | ID: mdl-35642147

RESUMO

Objective: To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease. Methods: Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells. Results: Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport. Conclusion: Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Animais , Chlorocebus aethiops , Enterovirus Humano A/genética , Células Vero , Virulência
7.
Bioorg Chem ; 108: 104641, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33517004

RESUMO

LC-MS guided chemical investigation of the periploside-rich extract of the root barks of Periploca sepium afforded six new minor pregnane glycosides, named periplosides A1-A6 (1-6). Their structures were characterized on the basis of extensive spectroscopic analysis. Compounds 1-6 were evaluated for their inhibitory activities against the proliferation of T and B lymphocytes in vitro, among them, compound 5 exhibited significant inhibitory activities and the most favorite selective index (SI) values against the proliferation of T lymphocyte (IC50 = 0.30 µM, SI = 176) and B lymphocyte (IC50 = 0.55 µM, SI = 97).


Assuntos
Linfócitos B/efeitos dos fármacos , Glicosídeos/farmacologia , Periploca/química , Raízes de Plantas/química , Pregnanos/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Glicosídeos/química , Glicosídeos/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Pregnanos/química , Pregnanos/isolamento & purificação , Relação Estrutura-Atividade
8.
Hepatology ; 69(5): 2076-2090, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586158

RESUMO

Portal vein tumor thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch of the main portal vein (MPV) or above could benefit from negative margin (R0) liver resection (LR). An Eastern Hepatobiliary Surgery Hospital (EHBH)/PVTT scoring system was established to predict the prognosis of HCC patients with PVTT after R0 LR and guide selection of subgroups of patients that could benefit from LR. HCC patients with PVTT limited to a first-order branch of the MPV or above who underwent R0 LR as an initial therapy were included. The EHBH-PVTT score was developed from a retrospective cohort in the training cohort using a Cox regression model and validated in a prospective internal validation cohort and three external validation cohorts. There were 432 patients in the training cohort, 285 in the prospective internal validation cohort, and 286, 189, and 135 in three external validation cohorts, respectively. The score was calculated using total bilirubin, α-fetoprotein (AFP), tumor diameter, and satellite lesions. The EHBH-PVTT score differentiated two groups of patients (≤/>3 points) with distinct long-term prognoses (median overall survival [OS], 17.0 vs. 7.9 months; P < 0.001). Predictive accuracy, as determined by the area under the time-dependent receiver operating characteristic curves (AUCs; 0.680-0.721), was greater than that of the other commonly used staging systems for HCC and PVTT. Conclusion: The EHBH-PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR. It selected appropriate HCC patients with PVTT limited to a first-order branch of the MPV or above for LR. It can be used to supplement the other HCC staging systems.


Assuntos
Carcinoma Hepatocelular/cirurgia , Técnicas de Apoio para a Decisão , Hepatectomia , Neoplasias Hepáticas/cirurgia , Trombose/etiologia , Adulto , Carcinoma Hepatocelular/complicações , Feminino , Humanos , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Veia Porta , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
BMC Urol ; 20(1): 100, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677927

RESUMO

BACKGROUND: To investigate the value of using contrast-enhanced transrectal ultrasound (CETRUS) to reduce unnecessary collection of biopsies during prostate cancer diagnosis and its utility in predicting biochemical recurrence in patients with localized prostate cancer. METHODS: This was a prospective study of suspected prostate cancer patients who were evaluated with CETRUS followed by a prostate biopsy. Prostate blood flow via CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcome was then analyzed for all patients; univariate and multi-variate analyses were used to determine the probable prognostic factors for biochemical recurrence in patients with localized prostate cancer that underwent a radical prostatectomy. RESULTS: A total of 347 patients were enrolled in the study. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer incidence. Using CETRUS scores ≥2 as the threshold for when to biopsy could have safely reduced the number of biopsies taken overall by 12.1% (42/347) and spared 23.0% (42/183) of patients from undergoing an unnecessary biopsy. 77 patients with localized prostate cancer underwent a radical prostatectomy. The median follow-up time was 30 months (range: 8-56 months) and 17 of these 77 patients exhibited biochemical recurrence during the follow-up period. 3-year biochemical recurrence-free survival rates were 86% for patients with low CETRUS scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis indicated that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00-24.69; p = 0.002). CONCLUSIONS: CETRUS scores may be a useful tool for reducing the collection unnecessary biopsy samples during prostate cancer diagnosis and are predictive of biochemical recurrence in patients with localized prostate cancer following a radical prostatectomy.


Assuntos
Neoplasias da Próstata/diagnóstico por imagem , Procedimentos Desnecessários/estatística & dados numéricos , Idoso , Biópsia/estatística & dados numéricos , Meios de Contraste , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Reto , Ultrassonografia/métodos
10.
HPB (Oxford) ; 22(7): 1025-1033, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31732465

RESUMO

BACKGROUND: The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). METHODS: The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). CONCLUSION: Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/cirurgia
11.
Lancet Oncol ; 20(4): 591-600, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30880070

RESUMO

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único/genética , Área Sob a Curva , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Nomogramas , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
12.
Oncologist ; 24(12): e1476-e1488, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31138726

RESUMO

BACKGROUND: Microvascular invasion (MVI) is associated with poor postoperative survival outcomes in patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis in patients with HCC with MVI after R0 liver resection (LR) and to supplement the most commonly used classification systems. MATERIALS AND METHODS: Patients with HCC with MVI who underwent R0 LR as an initial therapy were included. The EHBH-MVI score was developed from a retrospective cohort from 2003 to 2009 to form the training cohort. The variables associated with overall survival (OS) on univariate analysis were subsequently investigated using the log-rank test, and the EHBH-MVI score was developed using the Cox regression model. It was validated using an internal prospective cohort from 2011 to 2013 as well as three independent external validation cohorts. RESULTS: There were 1,033 patients in the training cohort; 322 patients in the prospective internal validation cohort; and 493, 282, and 149 patients in the three external validation cohorts, respectively. The score was developed using the following factors: α-fetoprotein level, tumor encapsulation, tumor diameter, hepatitis B e antigen positivity, hepatitis B virus DNA load, tumor number, and gastric fundal/esophageal varicosity. The score differentiated two groups of patients (≤4, >4 points) with distinct long-term prognoses outcomes (median OS, 55.8 vs. 19.6 months; p < .001). The predictive accuracy of the score was greater than the other four commonly used staging systems for HCC. CONCLUSION: The EHBH-MVI scoring system was more accurate in predicting prognosis in patients with HCC with MVI after R0 LR than the other four commonly used staging systems. The score can be used to supplement these systems. IMPLICATIONS FOR PRACTICE: Microvascular invasion (MVI) is a major determinant of survival outcomes after curative liver resection for patients with hepatocellular carcinoma (HCC). Currently, there is no scoring system aiming to predict prognosis of patients with HCC and MVI after R0 liver resection (LR). Most of the widely used staging systems for HCC do not use MVI as an independent risk factor, and they cannot be used to predict the prognosis of patients with HCC and MVI after surgery. In this study, a new Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis of patients with HCC and MVI after R0 LR. Based on the results of this study, postoperative adjuvant therapy may be recommended for patients with HCC and MVI with an EHBH-MVI score >4. This score can be used to supplement the currently used HCC classifications to predict postoperative survival outcomes in patients with HCC and MVI.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Hospitais , Humanos , Neoplasias Hepáticas/patologia , Masculino , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos
13.
Ann Surg Oncol ; 26(12): 4117-4125, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31321582

RESUMO

BACKGROUND: Microvascular invasion (MVI) predicts poor prognosis in patients with hepatocellular carcinoma (HCC). HCC patients with hypercoagulability are prone to develop thrombosis; however, the relationship between preoperative coagulability state, as reflected by the international normalized ratio (INR) level, and MVI remains unclear. METHODS: From January 2009 to December 2012, HCC patients who underwent R0 liver resection (LR) from four cancer centers entered into this study. The overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the 2509 HCC patients who were included into this study, 1104 were found to have MVI in the resected specimens. These patients were divided into the low (n = 151), normal (n = 796), and high (n = 157) INR subgroups based on the preoperative INR levels. The low INR subgroup had a significantly higher incidence of MVI than the normal or high INR subgroups (61.6% vs. 41.6% vs. 44.6%; p < 0.001). HCC patients with MVI were significantly more likely to have a low preoperative INR level (p < 0.001); the INR level (p < 0.001) was an independent risk factor of OS and RFS. HCC patients with MVI in the low INR subgroup had significantly worse RFS and OS than the normal or high INR subgroups (median RFS 13.5 vs. 20.2 vs. 21.6 months, p < 0.001; median OS 35.5 vs. 59.5 vs. 57.0 months, p < 0.001). CONCLUSIONS: Preoperative hypercoagulability was associated with poor long-term prognosis in HCC patients with MVI after R0 LR.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/patologia , Microvasos/patologia , Recidiva Local de Neoplasia/patologia , Trombofilia/mortalidade , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/irrigação sanguínea , Recidiva Local de Neoplasia/cirurgia , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Trombofilia/fisiopatologia
14.
Ann Surg Oncol ; 26(5): 1465-1473, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30767178

RESUMO

BACKGROUND: Vascular invasion is a major determinant of survival outcomes after curative resection for hepatocellular carcinoma (HCC) patients. This study was designed to investigate the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with HCC with hepatic vein tumor thrombus (HVTT). METHODS: Data from patients who underwent LR for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-TACE after LR were compared with those who underwent LR alone. Propensity score matching (PSM) analysis was performed to match patients in a ratio of 1:1. RESULTS: All included 319 patients who underwent LR for HCC with HVTT, 134 underwent LR alone (the LR group), and 185 patients underwent in adjuvant TACE (the PA-TACE group). PSM matched 107 patients in two groups. The overall survival (OS) and recurrence-free survival (RFS) were significantly better for patients in the PA-TACE group than the LR group (for OS: before PSM, P < 0.001; after PSM, P = 0.004; for RFS: before PSM, P < 0.001; after PSM, P = 0.013), respectively. On subgroup analysis, equivalent acceptable results were obtained in patients with peripheral HVTT (pHVTT) and major HVTT (mHVTT). However, PA-TACE resulted in no survival benefits for patients when the HVTT had extended to the inferior vena cava (IVCTT). CONCLUSIONS: PA-TACE was associated with significantly better survival outcomes than LR alone for patients with HCC and HVTT (pHVTT and mHVTT). There was no survival benefits in patients whose HVTT had extended to form IVCTT.


Assuntos
Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/mortalidade , Hepatectomia/mortalidade , Veias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Cuidados Pós-Operatórios , Adjuvantes Imunológicos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Veias Hepáticas/patologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Hepatol Res ; 49(4): 441-452, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30549370

RESUMO

AIM: Because of the rarity of hepatic vein tumor thrombus (HVTT) in patients with hepatocellular carcinoma (HCC), little is known about HVTT. Thus, the survival benefit of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) for HCC patients with HVTT or inferior vena cava tumor thrombus (IVCTT) remains controversial. We aimed to explore the survival benefits of LR versus TACE for the treatment of these patients. METHODS: From 2012 to 2016, a total of 276 patients with HVTT or IVCTT who underwent liver resection or TACE were enrolled in this study. Patients in the LR group were matched at a 1:1 ratio with patients treated with TACE as an initial treatment (TACE group). Clinical characteristics, overall survival, and disease-free survival were analyzed. RESULTS: The median survival time in the LR group was 4.7 months longer than that in the TACE group before PSM (19.4 vs. 14.7 months, P = 0.006) and 6.9 months longer than that in the TACE group after PSM (20.9 vs. 14.0 months, P = 0.019). The median disease-free survival time in the LR group was 3.2 months longer than that in the TACE group before PSM (12.3 vs. 9.1 months, P = 0.038) and 5.8 months longer than that in the TACE group after PSM (13.0 vs. 7.2 months, P = 0.011). CONCLUSION: Liver resection provides a good prognosis for HCC patients with HVTT or IVCTT compared with patients undergoing TACE, and coexistence with portal vein tumor thrombus is the most important factor related to survival.

16.
Future Oncol ; 15(17): 2009-2018, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30931608

RESUMO

Aim: To study the expression of EIF5A2 in urinary tract urothelial carcinoma and its clinicopathological features and prognosis. Methods: EIF5A2 expression was detected via immunohistochemistry in 101 patients. Results: Kaplan-Meier analysis showed that the EIF5A2 low expression group had significantly longer overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001) than the EIF5A2 high expression group. The high expression of EIF5A2 significantly predict poor OS and PFS in the subset patients (p < 0.05). EIF5A2 was an independent prognostic factor for OS and PFS (p = 0.003 and p = 0.001). The established nomogram model and its calibration curve predicted the probability of survival accurately. Conclusion: EIF5A2 is a potential molecular marker of poor prognosis in urinary tract urothelial carcinoma.


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias Renais/patologia , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Ureterais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Pelve Renal/patologia , Pelve Renal/cirurgia , Masculino , Pessoa de Meia-Idade , Nefroureterectomia , Prognóstico , Intervalo Livre de Progressão , Ureter/patologia , Ureter/cirurgia , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/cirurgia , Fator de Iniciação de Tradução Eucariótico 5A
17.
HPB (Oxford) ; 21(8): 935-944, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30871805

RESUMO

BACKGROUND: The effect of microvascular invasion (MVI) on the postoperative long-term prognosis of solitary small hepatocellular carcinoma remains controversial. We compared the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma. METHODS: The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma from inception to November 1, 2018. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS: Fourteen studies involving 3033 patients were evaluated. A meta-analysis of all 14 studies suggested that the OS of the MVI-positive group was significantly worse than that of the MVI-negative group (HR = 2.39, 95% CI = 2.02-2.84, I2 = 22.8%; P < 0.001). Twelve studies were included in the meta-analysis of DFS, and MVI showed a worse prognosis (HR = 1.79, 95% CI = 1.59-2.02, I2 = 25.3%; P < 0.001). Subgroup analysis demonstrated that MVI still showed a negative effect on the long-term OS and DFS of patients with solitary small HCC measuring up to 2 cm, 3 cm, or 5 cm. CONCLUSION: Microvascular invasion was a risk factor for poorer prognosis for solitary small hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Causas de Morte , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Idoso , Carcinoma Hepatocelular/cirurgia , China , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Medição de Risco , Análise de Sobrevida , Fatores de Tempo
18.
HPB (Oxford) ; 21(3): 335-344, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30104175

RESUMO

BACKGROUND: Lymph node metastasis (LNM)has widely been recognized as a poor prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative prediction of LNM is important for clinicians to decide on treatment. This study was designed to develop a simple and convenient system to predict LNM. METHODS: Consecutive HCC patients who were suspected to have LNM were divided into a training, an internal validation and an external validation cohort. The receiver operating characteristic (ROC) analysis was used to determine the threshold value of the preoperative serological variables. A nomogram visualization system model was then established. RESULT: Of the 287 patients, there were 31 patients who had LNM (10.8%), and 21 of 203 patients (10.3%) were in the training cohort and 10 of 84 patients (11.9%) in the internal validation cohort. Sixteen of 176 patients (9.1%) in the external validation cohort had LNM. The serological indices including neutrophil/lymphocyte rate, age, platelet, prothrombin time, and total protein, were included in the nomogram. The areas of the ROC curve were 0.846, 0.679 and 0.738 in predicting LNM in the training cohort, the internal validation cohort and the external validation cohort, respectively. CONCLUSION: The scoring system constructed using the preoperative serological variables predicted LNM in HCC patients.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Adulto , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Medição de Risco
19.
HPB (Oxford) ; 21(12): 1687-1696, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31153833

RESUMO

BACKGROUND: Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). METHODS: The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. RESULTS: 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. CONCLUSIONS: PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Sorafenibe/uso terapêutico , Adulto , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Invasividade Neoplásica , Pontuação de Propensão , Estudos Retrospectivos
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 806-811, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31416507

RESUMO

OBJECTIVE: To explore the predictive significance of exhaled breath temperature (EBT) for airway inflammation changes in children with asthma. METHODS: A total of 60 children with asthma who met the inclusion criteria at the first visit were chosen as the asthma group, and 60 healthy children were selected as the control group. The EBT level was measured by the latest third-generation product (X-halo). The Childhood Asthma Control Test (C-ACT) score was recorded. EBT level and C-ACT score were compared between the asthma and control groups. At the subsequent visit one month later, the children were divided into well-controlled, partially-controlled, and uncontrolled groups according to their C-ACT scores. The EBT level and the FeNO level of the three groups were measured. EBT level and C-ACT score were compared among the three groups. The correlation between EBT and FeNO was analyzed. The data of initial diagnosis were reviewed, the EBT level and C-ACT score at the first visit were compared among the three groups, and the differences in EBT level and C-ACT score among the three groups at the second and first visits were evaluated. RESULTS: At the first visit, the asthma group had a significantly higher EBT and a significantly lower C-ACT score compared with the control group (P<0.05). At the time of the subsequent visit, there was a significant difference in EBT level between the three groups, i.e., uncontrolled group > partially-controlled group > well-controlled group (P<0.05), and there was also a significant difference in C-ACT score between the three groups, i.e., well-controlled group > partially-controlled group > uncontrolled group (P<0.05). There were no significant differences in EBT level and C-ACT score at the first visit between the three groups. From the first visit to the subsequent visit, EBT level was significantly decreased in the well-controlled group (P<0.05), but significantly increased in both partially-controlled group uncontrolled groups (P<0.05); C-ACT score was significantly increased in the well-controlled and partially-controlled groups (P<0.05), but significantly decreased in the uncontrolled group (P<0.05). EBT and FeNO levels at the subsequent visit were positively correlated with each other in the uncontrolled group (P<0.05). CONCLUSIONS: EBT has predictive significance for the changes in airway inflammation in children with asthma.


Assuntos
Asma , Testes Respiratórios , Criança , Humanos , Inflamação , Óxido Nítrico , Temperatura
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