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1.
Molecules ; 26(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672380

RESUMO

In the present study, a sunflower-like nanostructure array composed of a series of synaptic nanoparticles and nanospheres was manufactured through an efficient and low-cost colloidal lithography technique. The primary electromagnetic field contribution generated by the synaptic nanoparticles of the surface array structures was also determined by a finite-difference time-domain software to simulate the hotspots. This structure exhibited high repeatability and excellent sensitivity; hence, it was used as a surface-enhanced Raman spectroscopy (SERS) active substrate to achieve a rapid detection of ultra-low concentrations of Alpha-fetoprotein (AFP). This study demonstrates the design of a plasmonic structure with strong electromagnetic coupling, which can be used for the rapid detection of AFP concentration in clinical medicine.


Assuntos
Nanoestruturas/química , alfa-Fetoproteínas/análise , Coloides/química , Campos Eletromagnéticos , Tamanho da Partícula , Software , Análise Espectral Raman , Propriedades de Superfície
2.
ACS Appl Mater Interfaces ; 13(7): 8823-8831, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33583183

RESUMO

The detection of cancer biomarkers at an early stage of tumor development is vital for effective diagnosis and treatment of cancer. Current diagnostic tools can often detect cancer only when the biomarker levels are already too high, so that the tumors have spread and treatments are less effective. It is urgent therefore to develop highly sensitive assays for the detection of such biomarkers at the lowest possible concentration. In this context, we developed a sandwich immunoassay based on surface-enhanced Raman scattering (SERS) for the ultrasensitive detection of α-fetoprotein (AFP), which is typically present in human serum as a biomarker indicative of early stages of hepatocellular carcinoma. In the immunoassay design, molybdenum disulfide (MoS2) modified with a monoclonal antibody was used as a capture probe for AFP. A secondary antibody linked to an SERS-encoded nanoparticle was employed as the Raman signal reporter, that is, the transducer for AFP detection. The sandwich immunocomplex "capture probe/target/SERS tag" was deposited on a silicon wafer and decorated with silver-coated gold nanocubes to increase the density of "hot spots" on the surface of the immunosensor. The developed SERS immunosensor exhibits a wide linear detection range (1 pg mL-1 to 10 ng mL-1) with a limit of detection as low as 0.03 pg mL-1 toward AFP with good reproducibility (RSD < 6%) and stability. These parameters demonstrate that the proposed immunosensor has the potential to be used as an analytical platform for the detection of early-stage cancer biomarkers in clinical applications.


Assuntos
Dissulfetos/química , Ouro/química , Imunoensaio , Nanopartículas Metálicas/química , Molibdênio/química , Prata/química , alfa-Fetoproteínas/análise , Humanos , Tamanho da Partícula , Análise Espectral Raman , Propriedades de Superfície
3.
Medicine (Baltimore) ; 100(4): e24326, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530224

RESUMO

ABSTRACT: The spleen plays an important role in tumor progression and the curative effects of splenectomy before hepatectomy for hypersplenism and hepatocellular carcinoma (HCC) are not clear. We investigated whether splenectomy before hepatectomy increases survival rate among patients with HCC and hypersplenism compared with that of patients who underwent synchronous hepatectomy and splenectomy or hepatectomy alone.Between January 2011 and December 2016, 266 patients who underwent hepatectomy as a result of HCC and portal hypertension secondary to hepatitis were retrospectively analyzed. Their perioperative complications and survival outcome were evaluated.Patients underwent synchronous hepatectomy and splenectomy (H-S group) and underwent splenectomy before hepatectomy (H-preS group) exhibited significantly higher disease-free survival (DFS) rates than those of patients underwent hepatectomy alone (H-O group). The DFS rates for patients in the H-S group, H-preS group, and H-O group were 74.6%, 48.4%, 39.8%, and 80.1%, 54.2%, 40.1%, and 60.5%, 30.3%, 13.3%, at 1, 3, and 5 years after surgery, respectively. Tumor size, tumors number, and levels of alpha fetoprotein (AFP) were independent risk factors for DFS. Gender and tumor size were independent prognostic factor for overall survival (OS). The preoperative white blood cell (WBC) and platelet (PLT) counts were significantly higher in the H-preS group than in those of the H-S group and the H-O group. After operation, the WBC and PLT counts in the H-S group and H-preS groups were significantly higher compared to those of the H-O group.No matter splenectomy before hepatectomy or synchronous hepatectomy and splenectomy, hepatectomy with splenectomy may improve DFS rates in patients with HCC and hypersplenism, and splenectomy before hepatectomy alleviates hypersplenism without an increased surgical risk.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/mortalidade , Hiperesplenismo/cirurgia , Neoplasias Hepáticas/cirurgia , Esplenectomia/mortalidade , Adulto , Biomarcadores/sangue , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Hiperesplenismo/complicações , Hiperesplenismo/mortalidade , Contagem de Leucócitos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Esplenectomia/métodos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/análise
4.
Medicine (Baltimore) ; 100(1): e23678, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429736

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common type of malignant tumors in adults, and is the most common cause of death in people with cirrhosis. Both laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) are radical treatments for small HCC. However, there is no international standard for the treatment of small HCC, and it is still controversial to choose LH or RFA in treating small HCC. We try to carry out a randomized, controlled, prospective study to compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC. METHODS: This study is a single-center, evaluator-blinded, randomized, controlled clinical trial (RCT). The patients will be randomly divided into RFA group and LH group in a 1:1 ratio according to a computer-generated randomization list. Postoperative complications rates, Alpha fetoprotein (AFP), hospital stay, 1, 2, 3-year overall survival (OS) rates, disease-free survival (DFS) rates and all possible adverse events will be recorded. Statistical analyses will be performed with SPSS v22.0 software. CONCLUSIONS: The study will compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC. OSF REGISTRATION NUMBER: doi: 10.17605/OSF.IO/HNX2T.


Assuntos
Carcinoma Hepatocelular/cirurgia , Protocolos Clínicos , Hepatectomia/normas , Laparoscopia/normas , Ablação por Radiofrequência/normas , Adulto , China , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ablação por Radiofrequência/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , alfa-Fetoproteínas/análise
5.
Clin Biochem ; 89: 44-50, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309517

RESUMO

OBJECTIVES: The study compared the diagnostic efficiency of serum oligosaccharide chain (G-test) and alpha-fetoprotein (AFP) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: Serum samples from 100 patients (divided into five groups of 20 each, namely the hepatitis, liver cirrhosis, liver cancer, health, and interference groups) who were admitted to the Second Affiliated Hospital of Nanchang University from October 2019 to January 2020 were collected, and the levels of G-test and AFP were determined. The sensitivity and specificity of the two indicators were compared, and the receiver operating characteristic curve of the subjects was drawn to evaluate the diagnostic values of G-test and AFP for HCC. RESULTS: The diagnostic ability of G-test (area under the curve [AUC]: 0.88 ± 0.05) was better than that of AFP (AUC: 0.76 ± 0.05). When G-test and AFP were combined for detection, the AUC was larger than that of either indicator. The G-test was superior to AFP in the differential diagnosis of early HCC and cirrhosis. A combination of the two indicators (AUC: 0.769 ± 0.05) significantly improved the diagnostic rate for early HCC, indicating that G-test and AFP complemented each other. CONCLUSION: G-test was better than AFP for screening HCC in patients with chronic hepatitis B and cirrhosis. The combination of the two further improved the diagnostic rate of hepatitis B-related liver cancer. The G-test improves the screening rate of early HCC in patients with cirrhosis. Therefore, these markers are of great clinical significance and can improve the sensitivity of HCC detection and reduce missed diagnosis rates.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Neoplasias Hepáticas/diagnóstico , Oligossacarídeos/sangue , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
6.
Med Sci Monit ; 26: e927444, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320844

RESUMO

BACKGROUND Alpha-fetoprotein (AFP) is widely used to screen for hepatocellular carcinoma (HCC). However, the use of this biomarker has been challenged due to its low sensitivity and high rate of false negatives. In this study, we evaluated the diagnostic capability of cyclin D2 (CCND2) promoter methylation in patients with HCC related to hepatitis B virus (HBV). MATERIAL AND METHODS Using methylation-specific PCR and quantitative real-time PCR, we measured methylation status and mRNA levels of CCND2 in plasma and peripheral blood mononuclear cells (PBMCs) from 275 subjects: 75 patients with chronic hepatitis B (CHB), 47 with liver cirrhosis (LC), 118 with HCC, and 35 healthy controls (HCs). RESULTS The methylation rate of the CCND2 promoter was significantly higher in HCC patients than in patients without HCC (P<0.001). Furthermore, advanced HCC (TNM III/IV) was associated with a significantly higher frequency of CCND2 methylation and lower CCND2 mRNA levels than early-stage disease (TNM I/II; P<0.05). Combined measurement of CCND2 methylation and AFP yielded significantly higher sensitivity and area under the curve (AUC) than AFP alone in distinguishing patients with HCC from subjects with LC and CHB (P<0.001). CONCLUSIONS CCND2 methylation may be useful for predicting HCC progression. In addition, combined measurement of CCND2 methylation and AFP could serve as a non-invasive diagnostic marker for patients with HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Ciclina D2/genética , Metilação de DNA , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , alfa-Fetoproteínas/análise , Área Sob a Curva , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Leucócitos Mononucleares/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , RNA Mensageiro/análise , Sensibilidade e Especificidade
7.
Medicine (Baltimore) ; 99(42): e22782, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080748

RESUMO

INTRODUCTION: Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. PATIENT CONCERNS: Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. DIAGNOSIS: In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. INTERVENTIONS: In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. OUTCOMES: In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). LESSONS: This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/terapia , Hepatectomia , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Biomarcadores/análise , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , alfa-Fetoproteínas/análise
8.
Zhonghua Wai Ke Za Zhi ; 58(10): 776-781, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-32993265

RESUMO

Objective: To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC). Methods: The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 µg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ(2) test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results: The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter (r(2)=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter (r(2)=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP (P<0.01) . Conclusions: PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular , Neoplasias Hepáticas , Precursores de Proteínas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Protrombina , Estudos Retrospectivos , Adulto Jovem , alfa-Fetoproteínas/análise
9.
PLoS One ; 15(8): e0238078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845895

RESUMO

BACKGROUNDS AND AIMS: Because of the known limitations of ultrasonography (US) alone, we re-evaluated whether complimentary testing for serum alpha-fetoprotein (AFP) is helpful in surveilling for hepatocellular carcinoma (HCC) in high-risk populations. METHODS: We included, from a hospital-based cancer registry, 1,776 asymptomatic adults who were surveilled biannually with the AFP test and US and eventually diagnosed with HCC between 2007 and 2015. Based on the screening results, these patients were divided into three groups: AFP (positive for AFP only; n = 298 [16.8%]), US (positive for US only; n = 978 [55.0%]), and AFP+US (positive for both; n = 500 [28.2%]). We compared the outcomes of the three groups, calculating the survival of the AFP group both as observed survival and as survival corrected for lead-time. RESULTS: In terms of tumor-related factors, the separate AFP and US groups were more likely to have early stage HCC and to receive curative treatments than the combined AFP+US group (Ps<0.05). The AFP group had significantly better overall and cancer-specific survival than the AFP+US group after adjusting for covariates (adjusted hazard ratios [HRs] 0.68 and 0.62, respectively). In analyses correcting for lead-time in the AFP group (doubling time 120 days), the respective adjusted HRs for the AFP group were unchanged (0.74 and 0.67), but they were no longer significant after additional adjustment for tumor stage and curative treatment (0.87 and 0.81). CONCLUSIONS: HCC cases detected by the AFP test without abnormal ultrasonic findings appear to have better survival, possibly as a result of stage migration and the resulting cures. Complementary AFP surveillance, together with US, could be helpful for at-risk patients.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Detecção Precoce de Câncer , Feminino , Hepatite B/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Ultrassonografia
10.
PLoS One ; 15(8): e0237475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790728

RESUMO

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors. METHODS: We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors. RESULTS: The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development. CONCLUSION: Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Incidência , Isoquinolinas/uso terapêutico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , alfa-Fetoproteínas/análise
12.
PLoS One ; 15(7): e0235576, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614912

RESUMO

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels. METHODS: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence. RESULTS: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5. CONCLUSION: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
13.
Aliment Pharmacol Ther ; 52(2): 359-370, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32519782

RESUMO

BACKGROUND: We conducted a prospective study using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to determine whether sustained virological response (SVR) by direct-acting anti-viral (DAA) drugs suppresses hepatocarcinogenesis in patients with hepatitis C virus (HCV) infection. AIM: To use serial Gd-EOB-MRI to assess the impact of DAAs on hepatocarcinogenesis. METHODS: Between February 2008 and December 2018, 1083 consecutive patients with HCV infection underwent Gd-EOB-MRI. Of these, 719 patients were enrolled, including 210 patients in the 'Non-DAA group', who did not receive DAAs before the introduction of DAAs, and 509 patients in the 'DAA group', who achieved SVR after the introduction of DDAs. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. In addition, hepatocarcinogenesis was classified into two types, 'multistep' and 'de novo', on the basis of Gd-EOB-MRI findings. Factors associated with each type were analysed by Fine and Gray proportional hazards models. RESULTS: Hepatocarcinogenesis was observed in 67 of 719 (9.3%) patients. Factors associated with hepatocarcinogenesis were male gender, albumin-bilirubin (ALBI) grade 2 or 3, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) ≥5%, the presence of nonhypervascular hypointense nodules (NHHNs) and Non-DAA group. Of 67 patients, multistep hepatocarcinogenesis occurred in 58 patients (86.6%) and de novo hepatocarcinogenesis occurred in nine patients (13.4%). Factors associated with multistep hepatocarcinogenesis were male gender and Non-DAA group. CONCLUSION: The eradication of HCV by DAA therapy reduces multistep hepatocarcinogenesis.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Idoso , Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/virologia , Meios de Contraste , Feminino , Seguimentos , Gadolínio DTPA , Hepatite C/diagnóstico por imagem , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/virologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Albumina Sérica/análise , Caracteres Sexuais , Resposta Viral Sustentada , alfa-Fetoproteínas/análise
14.
Acta Obstet Gynecol Scand ; 99(10): 1346-1353, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32356359

RESUMO

INTRODUCTION: Preeclampsia affects about 10% of twin pregnancies and significantly increases the risk of adverse pregnancy outcomes. However, screening models for preeclampsia in twin pregnancies remain elusive. The present study aimed to evaluate the performance of a multi-marker first trimester preeclampsia screening model in low-risk twin pregnancies. MATERIAL AND METHODS: Between 2014 and 2017, we prospectively assessed first trimester biomarkers for preeclampsia in a 'low-risk' twin pregnancy cohort at a single center. Multiple logistic regression was used to determine significant predictors for early preeclampsia (occurring prior to 34 weeks) and late preeclampsia (occurring after 34 weeks). The performance of the screening models fitted using the significant predictors was calculated using receiver operating characteristics curves, and internal validation was performed using bootstrapping. RESULTS: A total of 769 twin pregnancies were included in the study. Early preeclampsia and late preeclampsia developed in 27 (3.5%) and 59 (7.7%) cases, respectively. Logistic regression analyses showed that maternal age, body mass index, mean artery pressure and placental growth factor were significant predictors for early preeclampsia. Maternal age, body mass index, mean artery pressure and pregnancy-associated plasma protein A were significant for late preeclampsia. Uterine artery pulsatility index was not predictive of either early or late preeclampsia. For the fitted screening model of early and late preeclampsia, the areas under receiver operating characteristics curves were 0.82 (95% confidence interval [CI] 0.76-0.88) and 0.66 (95% CI 0.59-0.73), which were expected to decrease to 0.77 and 0.60, respectively, based on bootstrapping; the positive predictive values were 10.2% and 12.5%; and the estimated detection rates were 40.7% and 22.0%, respectively, at a false-positive rate of 10%. CONCLUSIONS: A multi-marker screening model for preeclampsia in low-risk twin pregnancies, using a modified version of Fetal Medicine Foundation predictors in singletons, does not perform well. Uterine artery pulsatility index is of little value in screening for preeclampsia in low-risk twin pregnancies.


Assuntos
Pré-Eclâmpsia/diagnóstico , Primeiro Trimestre da Gravidez , Gravidez de Gêmeos , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Índice de Massa Corporal , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Idade Materna , Pré-Eclâmpsia/sangue , Valor Preditivo dos Testes , Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Estudos Prospectivos , Fluxo Pulsátil , Ultrassonografia Doppler , Artéria Uterina/diagnóstico por imagem , alfa-Fetoproteínas/análise
15.
Medicine (Baltimore) ; 99(20): e20326, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443384

RESUMO

The hypomethylation of the Cyclin D1 (CCND1) promoter induced by excess oxidative stress likely promotes the development of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). We aimed to evaluate methylation status of the CCND1 promoter as a new plasma marker for the detection of HBV-HCC.We consecutively recruited 191 participants, including 105 patients with HBV-HCC, 54 patients with chronic hepatitis B (CHB), and 32 healthy controls (HCs). Using methylation-specific polymerase chain reaction, we identified the methylation status of the CCND1 promoter in plasma samples. We analyzed the expression levels of the CCND1 mRNA in peripheral blood mononuclear cells by using quantitative real-time PCR. We assessed the plasma levels of superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde by using enzyme-linked immunosorbent assays.Patients with HBV-HCC (23.81%) presented a reduced methylation frequency compared with patients with CHB (64.81%) or HCs (78.13%) (P < .001). When receiver operating characteristic curves were plotted for patients with HBV-HCC versus CHB, the methylation status of the CCND1 promoter yielded diagnostic parameter values for the area under the curve of 0.705, sensitivity of 76.19%, and specificity of 64.81%, thus outperforming serum alpha-fetoprotein (AFP), which had an area under the curve of 0.531, sensitivity of 36.19%, and specificity of 90.74%. Methylation of the CCND1 promoter represents a prospective diagnostic marker for patients with AFP-negative HBV-HCC and AFP-positive CHB. The expression levels of CCND1 mRNA was increased in patients with HBV-HCC compared with patients with CHB (Z = -4.946, P < .001) and HCs (Z = -6.819, P < .001). Both the extent of oxidative injury and antioxidant capacity indicated by the superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde levels were increased in patients with HBV-HCC. Clinical follow up of patients with HBV-HCC revealed a worse overall survival (P = .012, log-rank test) and a decreased progression-free survival (HR = 0.109, 95%CI: 0.031-0.384) for the unmethylated CCND1 group than methylated CCND1 group.Our study confirms that oxidative stress appears to correlate with plasma levels of CCND1 promoter methylation, and the methylation status of the CCND1 promoter represents a prospective biomarker with better diagnostic performance than serum AFP levels.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/fisiopatologia , Ciclina D1/metabolismo , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/fisiopatologia , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Metilação de DNA/fisiologia , Detecção Precoce de Câncer , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Regiões Promotoras Genéticas/fisiologia , Estudos Prospectivos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Superóxido Dismutase/metabolismo , alfa-Fetoproteínas/análise
16.
Klin Lab Diagn ; 65(6): 353-357, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32459893

RESUMO

Comparative analysis of serum concentrations of chorionic gonadotropin (hCG) associated with the pregnancy of plasma protein A (PAPP-A) and alpha-fetoprotein (AFP), based on the results of a survey of women as part of a standard screening program (the results were expressed as a MoM - multiply of the median), found a significant increase in the performance of all the studied specific pregnancy proteins in women with a scar on the uterus and placenta acctera (75 patients) compared with the data of the group of pregnant women without scar on the uterus and without abnormalities of attachment of the placenta (150 women). AFP indices were 1.68 ± 0.76 and 1.19 ± 0.43 MoM (p = 0.0018), hCG - 1.62 ± 1.48 and 1.23 ± 0.76 MoM (p = 0, 0112), PAPP-A - 1.93 ± 1.24 and 1.23 ± 0.67 MoM (p <0.0001). Using the ROC analysis, the diagnostic thresholds for the concentrations of AFP, hCG and PAPP-A were calculated. The risk of placenta accreta in women with a scar on the uterus in cases of exceeding the diagnostic threshold of AFP concentration (1.64 MoM) increased 2.5 times (RR = 2.5; 95% CI 1.17-5.36, p = 0, 0185), hCG (1.41 MoM) - 1.6 times (RR = 1.59; 95% CI 1.09-2.32, p = 0.0147), PAPP-A (1.41 MoM) - 2.65 times (RR = 2.65; 95% CI 1.76-3.99, p <0.0001). Determination of the level of specific pregnancy proteins can be used in the system of complex prediction of placental growth in pregnant women with a scar on the uterus as an addition to the assessment of clinical and anamnestic risk factors.


Assuntos
Gonadotropina Coriônica/sangue , Cicatriz/patologia , Placenta Acreta/diagnóstico , Proteína Plasmática A Associada à Gravidez/análise , Útero/patologia , alfa-Fetoproteínas/análise , Biomarcadores/sangue , Gonadotropina Coriônica Humana Subunidade beta , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Prognóstico
17.
Environ Toxicol ; 35(9): 971-981, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32302048

RESUMO

Hepatocellular carcinoma (HCC) ranks the sixth position among various cancers worldwide. Recent research shows that natural and dietary compounds possess many therapeutic effects. Citral is a monoterpene aldehyde that contains geranial and neral. The present study was considered to study the role of citral against N-nitrosodiethylamine (NDEA)-induced HCC via modulation of antioxidants and xenobiotic-metabolizing enzymes in vivo. NDEA-alone-administered group II animals profoundly showed increased tumor incidence, reactive oxygen species, liver marker enzyme levels, serum bilirubin levels, tumor markers of carcinoembryonic antigen, α-fetoprotein, proliferative markers of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen (PCNA) expressions, phase I xenobiotic-metabolic enzymes and simultaneously decreased antioxidants, and phase II enzymes levels. Citral (100 mg/kg b.w.) treatment significantly reverted the levels in group III cancer-bearing animals when compared to group II cancer-bearing animals. In group IV animals, citral-alone administration did not produce any adverse effect during the experimental condition. Based on the results, citral significantly inhibits the hepatocellular carcinogenesis through restoring the antioxidants and phase II xenobiotic-enzyme levels; thereby, it strongly proves as an antiproliferative agent against rat HCC.


Assuntos
Monoterpenos Acíclicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Animais , Antígeno Carcinoembrionário/análise , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Dietilnitrosamina , Humanos , Testes de Função Hepática , Neoplasias Hepáticas Experimentais/enzimologia , Neoplasias Hepáticas Experimentais/patologia , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , alfa-Fetoproteínas/análise
18.
Monaldi Arch Chest Dis ; 90(1)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268717

RESUMO

Testicular carcinoma recurrences represent a rare finding (1-6% in non-seminomatous germ cell tumours). However, cases of recurrence have been described many years later. We report a case of late recurrence of embryonic testicular carcinoma, after 26 years, with pulmonary metastases. Following evidence of increase of alpha-fetoprotein (AFP), the patient underwent a total body computed tomography scan that exhibited two pulmonary nodules, one in upper left lobe and other in left hilar region with multiple mediastinal and retrocrural lymph node enlargements All consolidations showed increased sugar uptake value at PET CT. Biopsies of lung consolidations confirmed diagnosis of recurrence of testicular carcinoma.


Assuntos
Carcinoma Embrionário/patologia , Neoplasias Pulmonares/secundário , Neoplasias Testiculares/patologia , Biópsia , Carcinoma Embrionário/sangue , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/sangue , Fatores de Tempo , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/análise
19.
Zhonghua Yi Xue Za Zhi ; 100(11): 864-867, 2020 Mar 24.
Artigo em Chinês | MEDLINE | ID: mdl-32234160

RESUMO

Objective: To investigate the accuracy and safety of ultrasound-guided puncture biopsy and enhanced MRI in the diagnosis of alpha-fetoprotein (AFP) negative liver occupying lesions. Methods: Retrospective analysis was conducted on the clinical data of 59 patients with liver occupying lesions who were admitted to the Fifth Medical Center of the PLA General Hospital from February 2015 to November 2017 and received ultrasound-guided coarse needle biopsy with AFP negative. Among them, 35 cases were males and 24 cases were females, the age range was from 25 to 67 years,with an average age of (51±3) years. Serum AFP in all patients were within the normal range. The difference between the pathological results of ultrasound-guided biopsy and the diagnosis of lesions by enhanced MRI was compared, and the diagnostic value of ultrasound-guided biopsy was analyzed. Meanwhile, complications during and after puncture were recorded. SPSS 24.0 software was used for statistical analysis.The measurement data were expressed as x±s and enumeration data were expressed as rate,if the P value was less than 0.05, it indicated that the difference was statistically significant. Results: There were 32 malignant cases and 27 benign cases based on the final pathological diagnosis. The sensitivity and specificity of ultrasound-guided needle biopsy were 100%, in contrast, the enhanced MRI was 96.9% and 81.5%, respectively, with the former significantly higher than the latter. There were no abdominal bleeding,infections and pneumothoraxduring and after the puncture. Conclusion: Ultrasound-guided puncture biopsy and enhanced MRI are both safe for the diagnosis of AFP negative liver occupying lesions,but the former is more sensitive than the latter.When the clinical symptoms of the patient are relatively mild and there is uncertainty in the diagnosis due to the lack of specific enhanced imaging, ultrasound-guided puncture is more conducive to identifying the nature of the lesion.


Assuntos
Biópsia por Agulha/métodos , Hepatopatias/diagnóstico , Ultrassonografia de Intervenção , Adulto , Idoso , Feminino , Humanos , Fígado , Masculino , Pessoa de Meia-Idade , Punções , Estudos Retrospectivos , Sensibilidade e Especificidade , alfa-Fetoproteínas/análise
20.
PLoS One ; 15(3): e0230005, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163475

RESUMO

BACKGROUND AND AIMS: The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafeninb is one of the recommended therapies. We aim to evaluate the real world clinical treatment and survival of BCLC stage C patients in an Asian cohort. METHODS: This is a retrospective cohort study that enrolled 427 consecutive BCLC stage C patients diagnosed between 2011 and 2017 by using the HCC registry data for our hospital. All patients were managed via a multidisciplinary team (MDT) approach. RESULTS: Hepatitis B surface antigen positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n = 83; 19.4%), PS2 alone (n = 23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n = 321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type. CONCLUSIONS: We reported the real world management in BCLC stage C patients in an Asian cohort through the use of personalized management via a MDT approach.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sorafenibe/uso terapêutico , Análise de Sobrevida , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/secundário , alfa-Fetoproteínas/análise
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