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1.
BMC Med ; 20(1): 8, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-35027051

RESUMO

BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).


Assuntos
Carcinoma Hepatocelular , Ácidos Nucleicos Livres , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Ácidos Nucleicos Livres/genética , Metilação de DNA , Diagnóstico Diferencial , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética
2.
Sensors (Basel) ; 21(7)2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33916389

RESUMO

The credibility of sensor data is essential for security monitoring. High-credibility data are the precondition for utilizing data and data analysis, but the existing data credibility evaluation methods rarely consider the spatio-temporal relationship between data sources, which usually leads to low accuracy and low flexibility. In order to solve this problem, a new credibility evaluation method is proposed in this article, which includes two factors: the spatio-temporal relationship between data sources and the temporal correlation between time series data. First, the spatio-temporal relationship was used to obtain the credibility of data sources. Then, the combined credibility of data was calculated based on the autoregressive integrated moving average (ARIMA) model and back propagation (BP) neural network. Finally, the comprehensive data reliability for evaluating data quality can be acquired based on the credibility of data sources and combined data credibility. The experimental results show the effectiveness of the proposed method.

3.
Avian Pathol ; 49(6): 557-571, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32658552

RESUMO

Since 2017, novel variant strains of infectious bursal disease virus (nvIBDV) have been detected in China, while the current vaccines on the market against very virulent IBDV have limited protection against this subtype virus. In this context, a strain of the virus has been isolated, and sequencing alignment and bird regression experiments showed that the virus was IBDV, belonging to the nvIBDV subtype (and named IBDV FJ-1812). Furthermore, the Escherichia coli expression system was used to successfully express soluble nvIBDV rVP2, which is specifically recognized by an anti-IBDV standard serum and anti-nvIBDV positive serum, and could be assembled into 14 - 17 nm virus-like particles. Based on the purified nvIBDV rVP2, we developed an IBDV FJ-1812 VP2 VLP vaccine at a laboratory scale to evaluate protection by this vaccine; in addition, we also prepared an IBDV JZ 3/02 VP2 subunit vaccine targeting very virulent IBDV and evaluated its cross-protection against nvIBDV. Results of bird experiments showed that the nvIBDV rVP2 vaccine could induce high titres of specific antibodies, completely protect the bursa of Fabricius from viral infection, and provide 100% immune protection to SPF and Ross 308 broiler chickens. Furthermore, the IBDV JZ 3/02 VP2 subunit vaccine targeting very virulent IBDV could provide 60% protection for SPF chickens and 80% protection for Ross 308 broiler chickens. This report provides important technical supports for the prevention and control of nvIBDV in the future.


Assuntos
Infecções por Birnaviridae/veterinária , Galinhas/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Doenças das Aves Domésticas/prevenção & controle , Proteínas Estruturais Virais/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Birnaviridae/prevenção & controle , Infecções por Birnaviridae/virologia , Galinhas/virologia , Proteção Cruzada , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Imunogenicidade da Vacina , Vírus da Doença Infecciosa da Bursa/genética , Filogenia , Doenças das Aves Domésticas/virologia , Vacinas Sintéticas , Carga Viral/veterinária , Proteínas Estruturais Virais/genética
4.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(9): 1020-1025, 2018 Sep 28.
Artigo em Chinês | MEDLINE | ID: mdl-30333295

RESUMO

OBJECTIVE: To explore the feasibility and efficacy of isolated caudate lobe resection for caudate lobe in huge hepatocellular carcinoma(10 cm or larger in diameter).
 Methods: Clinical data of 27 patients with hepatocellular carcinoma larger than 10 cm who underwent isolated caudate lobe resection from January 2001 to December 2011 were retrospectively analyzed.
 Results: All the patients successfully completed the operation. There was no postoperative death. Median operative time was 288 min, and the estimated intraoperative blood loss was 2 260 mL. Postoperative morbidity rate was 44.4%. The patients were discharged successfully after active treatment. Overall survival rates at 1, 3, and 5 years were 80.2%, 52.1%, and 27.1%, respectively.
 Conclusion: Isolated caudate lobe resection is safe and effective for caudate lobe huge hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 39(9): 879-82, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25269496

RESUMO

OBJECTIVE: To explore the technique and effect of liver hanging maneuver in anterior approach for isolated complete liver caudate lobectomy. METHODS: We recruited 17 patients with liver caudate lobe tumor (13 primary hepatocellular carcinoma, 3 cholangiocarcinoma and 1 liver metastasis from colorectal cancer). Isolated complete caudate lobectomy with liver hanging maneuver was performed in 17 patients. RESULTS: All 17 patients were successfully received the above-mentioned operation. The operative time was 166-427 (211.5 ± 20.1) min and the intraoperative blood loss was 372-1 208 (472.7 ± 83.6) mL. There was no operative death. The survival rates of follow up for 1, 3 and 5 years were 76.5%, 52.9% and 23.5%, respectively. CONCLUSION: Liver hanging maneuver for isolated complete resection of the caudate lobe is an ideal approach for liver neoplasms resection.


Assuntos
Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Perda Sanguínea Cirúrgica , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/secundário , Taxa de Sobrevida
6.
Hepatogastroenterology ; 59(118): 1706-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22193437

RESUMO

BACKGROUND/AIMS: Preservation of functional liver parenchyma should be a priority in hepatic surgery to avoid postoperative liver failure and enhance the opportunity to perform repeat resection in case of tumor recurrence. METHODOLOGY: A tumor localized in segments VII, VIII and adhering to or compressing the middle hepatic vein sometimes indicates a need to perform bisegmentectomy VII-VIII without surgical margin. From June 2006 to June 2011, fourteen patients with such a tumor underwent null-margin bisegmentectomy VII-VIII in our hospital. We retrospectively review our experience with this uncommon and technique-challenging hepatic resection. RESULTS: Mean intraoperative blood loss was estimated to be 300 mL and only four patients required blood transfusions less than 4U each person. Mean postoperative hospitalization was 11.2 days. Postoperative complications were encountered in 28.5% of patients and there was no postoperative mortality. Median overall and disease-free survivals were 35 and 23 months, respectively. CONCLUSIONS: The lack of ability to obtain an adequate surgical margin should not be considered as a contraindication for hepatectomy of HCC. In patients with impaired liver functional reserve and with right superiorly located tumors, the preservation of the middle hepatic vein should take priority and null-margin bisegmentectomy VII-VIII for HCC should be recommended.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Veias Hepáticas/cirurgia , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , China , Intervalo Livre de Doença , Hepatectomia/efeitos adversos , Veias Hepáticas/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Ann Transl Med ; 10(22): 1237, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36544691

RESUMO

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications. Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards. Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches. Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists.

8.
Hepatogastroenterology ; 58(106): 318-23, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21661389

RESUMO

BACKGROUND/AIMS: Mesohepatectomy is rarely used to treat central liver tumors because of its technical complexity. This retrospective study aimed to evaluate the application of irregular mesohepatectomy with alternating regional blood occlusion for central liver tumors. METHODOLOGY: From 2003 to 2008, 128 patients with central liver tumors were treated by irregular mesohepatectomy (Group I, n=85) and anatomic mesohepatectomy (Group II, n=43) respectively. The clinical profiles and follow-up data, including the operation time, bleeding volume, blood transfusion volume, postoperative recovery of liver function and postoperative complications, were compared among the two groups. Kaplan-Meier analysis was made for survival rates comparison. RESULTS: The average operative durations were 195.1 +/- 52.4 min and 264.3 +/- 57.3 min in Group I and Group II, respectively. There was significant difference between the two groups in incidence of postoperative biliary fistula (18.8% vs 9.3%, p<0.05), but not in bleeding volume, blood transfusion volume, post-operative LFT changes and 1, 3 and 5-year survival rates. Kaplan-Meier survival analysis showed no significant difference between the two groups on survival rate. CONCLUSION: Irregular mesohepatectomy with alternating regional blood occlusion can achieve an efficacy comparable to anatomic mesohepatectomy.


Assuntos
Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Alanina Transaminase/sangue , Transfusão de Sangue , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida
9.
Hepatogastroenterology ; 58(106): 575-82, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21661434

RESUMO

BACKGROUND/AIMS: Anatomic mesohepatectomy is often anatomically restricted by the hilar structure and, therefore, difficult to perform with an adequate resection margin. Especially, in the case of a tumor which is in contact without infiltration with the critical intrahepatic vessels, mesohepatectomy has to be performed without a surgical margin. METHODOLOGY: From January 2005 to December 2009, thirty-seven patients with centrally located HCC underwent anatomic mesohepatectomy without resection margin in our hospital. The surgical techniques, clinicopathological characteristics and outcomes were reviewed. RESULTS: Mean operative time was 210 minutes (range 130 to 310 minutes) and mean intraoperative blood loss was 950 mL (range 150 to 4,500 mL). Mean postoperative hospitalization was 12.6 days (range 10 to 32 days). Postoperative complications were encountered in 37.8% of patients. The 1-, 3-, and 5-year recurrence-free survival rate was 75.1%, 39.3%, 22.5%, respectively, and the 1-, 3- and 5-year overall survival rate was 91.9%, 60.4%, 28.5%, respectively. CONCLUSION: Null-margin mesohepatectomy is an oncologically radical but parenchyma-sparing hepatic resection. In patients with impaired functional liver reserve and with centrally located tumors in contact without infiltration with major vessels, expected zero resection margins should not be considered as a contraindication for surgery, and null-margin mesohepatectomy should be recommended as a reasonable surgical option.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Hepatectomia/efeitos adversos , Humanos , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia
10.
J Vet Med Sci ; 83(8): 1263-1272, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34234054

RESUMO

The Cap of porcine circovirus type 2 (PCV2) can be assembled into virus like particles (VLPs) in vitro that have multiple loops located on the particle surface. This would make it a good vehicle for displaying exogenous proteins or epitopes. We derived two epitopes, epitope B (EpB, S37HIQLIYNL45) and epitope 7 (Ep7, Q196WGRL200) from Gp5 of the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). We replaced the core region of Loop CD (L75PPGGGSN82) and the carboxyl terminus (K222DPPL226) of PCV2 Cap, respectively, to construct a bi-epitope chimeric PCV2 Cap. Its immunogenicity and protective effects were evaluated as one PRRSV subunit vaccine. The chimeric PCV2 Cap was soluble, efficiently expressed in an Escherichia coli expression system, and could be self-assembled into chimeric virus like particles (cVLPs) with a diameter of 12-15 nm. Western blotting confirmed that the cVLPs could be specifically recognized by anti-PCV2, anti-EpB and anti-Ep7 antibodies. The cVLPs vaccine could alleviate the clinical symptoms and reduce the viral loads after HP-PRRSV challenge in 100-120 days old pigs. These data suggest that the cVLPs vaccine could provide pigs with partial protection against homologous PRRSV strains, and it provides a new design for additional PRRSV subunit vaccines.


Assuntos
Infecções por Circoviridae , Circovirus , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Vacinas Virais , Animais , Anticorpos Antivirais , Infecções por Circoviridae/prevenção & controle , Infecções por Circoviridae/veterinária , Circovirus/genética , Epitopos , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Suínos
11.
Virus Res ; 305: 198552, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34454971

RESUMO

Hepatitis-hydropericardium syndrome (HHS) is widespread in China and causes high chicken mortality that results in great economic losses. A safe and effective vaccine is needed, and a subunit vaccine has potential for development. In this study, a truncated region of the FAdV-4 fiber 2 fused with coding sequence of one epitope of hexon was expressed in a prokaryotic expression system, and the immune protective effects of different doses of recombinant fiber 2 subunit vaccine on SPF chickens were compared. The recombinant fiber2 (Gly275- Pro479 aa)-hexon (Met21-Val51 aa) protein (rFH) obtained in Escherichia coli showed good solubility. The chicken survival rate at the lowest dose (2.5 µg/bird) was 75% (6/8), and at higher doses (≥5 µg/bird) was 100% (8/8) in challenge experiment. Two chickens in the 2.5 µg/bird treatment showed severe lesions, while birds in the higher dose treatments showed no obvious tissue damage as determined by histopathologic analysis of liver and spleen. Absolute quantitative real-time PCR showed no viral load in the ≥5 µg/bird treatments, but two chickens in the 2.5 µg/bird treatment had high viral loads. The challenge experience demonstrated that the rFH vaccine provided 100% protection at ≥5 µg/bird. These results suggested that rFH protein as an effective vaccine to protect against FAdV-4 and provided a new idea for the development of vaccine against HHS.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves Domésticas , Adenoviridae , Infecções por Adenoviridae/prevenção & controle , Infecções por Adenoviridae/veterinária , Animais , Aviadenovirus/genética , Galinhas , Sorogrupo , Vacinas de Subunidades Antigênicas/genética
12.
Drug Deliv ; 28(1): 1722-1736, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34463179

RESUMO

Bioactive therapeutic molecules are generally impermeable to the cell membrane, hindering their utility and efficacy. A group of peptides called cell-penetrating peptides (CPPs) were found to have the capability of transporting different types of cargo molecules across the cell membrane. Here, we identified a short peptide named P2, which has a higher proportion of basic residues than the CDN1 (cyclin-dependent kinase inhibitor 1) protein it is derived from, and we used bioinformatic analysis and experimental validation to confirm the penetration property of peptide P2. We found that peptide P2 can efficiently enter different cell lines in a concentration-dependent manner. The endocytosis pathway, especially receptor-related endocytosis, may be involved in the process of P2 penetration. Our data also showed that peptide P2 is safe in cultured cell lines and red blood cells. Lastly, peptide P2 can efficiently deliver self-labeling protein HaloTag into cells for imaging. Our study illustrates that peptide P2 is a promising imaging agent delivery vehicle for future applications.


Assuntos
Transporte Biológico/fisiologia , Membrana Celular/metabolismo , Peptídeos Penetradores de Células/metabolismo , Animais , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/química , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Relação Dose-Resposta a Droga , Endocitose/fisiologia , Eritrócitos/metabolismo , Feminino , Hepatócitos , Humanos , Ratos
13.
J Med Microbiol ; 69(9): 1183-1196, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32812860

RESUMO

Introduction. PCV2 is a DNA virus that exists widely in pigs and has caused great economic losses to the pig industry worldwide. In the existing commercial PCV2 enzyme-linked immunosorbent assay (ELISA) kits both natural infection with PCV2 and vaccine immunization produce results that are positive for PCV2 Cap antibodies and therefore they cannot diagnose PCV2 infection in immunized pig farms.Aim. To establish a PCV2 non-structural protein antibody detection method that distinguishes between antibodies resulting from natural prior exposure (infection) and those induced by subunit vaccine immunization.Methodology. Based on the non-structural Rep' protein, we established an indirect ELISA (iELISA) using sera from guinea pigs and piglets.Results. The results for iELISA for guinea pig serum showed that animals vaccinated with a whole-virus inactivated PCV2 vaccine had 100 % (10/10) Cap antibody positivity and 100 % (10/10) Rep' antibody positivity. Guinea pigs vaccinated with a recombinant subunit PCV2 vaccine had 100 % (10/10) Cap antibody positivity, while no (0/10) guinea pigs were Rep' antibody-positive. The combined detection results for the Rep' iELISA and a PCV2 Antibody Test kit (Commercial) showed that pigs vaccinated with a whole-virus inactivated PCV2 vaccine or PCV2 SD/2017 had 100 % (5/5) Cap antibody positivity and 100 % (5/5) Rep' antibody positivity. Pigs vaccinated with a recombinant subunit PCV2 vaccine had 100 % (5/5) Cap antibody positivity, while no (0/10) pigs were Rep' antibody-positive.Conclusion. This paper describes an effective iELISA method that can distinguish natural infection with PCV2 (Cap and Rep positive) or inoculation with a whole-virus inactivated vaccine (Cap and Rep positive) from subunit vaccine immunization (Cap-positive, Rep-negative). These comparative assays could be very useful in the control of PCV2 in pig herds.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Circoviridae/sangue , Infecções por Circoviridae/veterinária , Circovirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Doenças dos Suínos/sangue , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/análise , Infecções por Circoviridae/imunologia , Circovirus/genética , Imunização , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
14.
Hepatogastroenterology ; 56(96): 1730-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20214226

RESUMO

BACKGROUND/AIMS: Intraoperative bleeding remains a major concern during mesohepatectomy because of doubled area of cut surface and proximity to important intrahepatic vascular structures. Preliminary extrahepatic exposure and looping of the main hepatic veins with the possibility of clamping them in association with total or partial vascular inflow occlusion, can lead to substantially reducing intraoperative bleeding. METHODOLOGY: From January 2003 to July 2008, preliminary exposure and looping of the main hepatic veins was performed in 67 patients undergoing mesohepatectomy. Among these patients, mesohepatectomy was performed with clamping of more than one of the main hepatic veins in 47 patients. We report the results obtained in those patients. RESULTS: Total vascular inflow occlusion with Pringle maneuver or partial vascular inflow occlusion based on an intrahepatic approach was used in all patients. The amount of intraoperative blood loss averaged (580 +/- 308) (range 180 to 4500) ml. No macroscopic tumor residue was encountered. There were no hospital deaths and the morbidity rate was 25.7%. The mean hospital stay was 11.2 days (range, 9-26). CONCLUSIONS: Our study showed that preliminary extrahepatic control of the main hepatic veins was a safe and technically feasible maneuver. During mesohepatectomy, clamping more than one of the main hepatic veins, in association with total or partial vascular inflow occlusion, is efficacious in reducing intraoperative bleeding.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Veias Hepáticas , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Hepatogastroenterology ; 56(90): 442-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19579617

RESUMO

BACKGROUND/AIMS: To evaluate the hemihepatic vascular occlusion with hanging maneuver in hepatectomy. METHODOLOGY: Ninety-four cases of hepatectomy were analyzed retrospectively. All patients were randomized into 3 groups: Pringle maneuver was applied in Group 1 (n=40), hemihepatic inflow control was Group 2 (n=30) and complete hemihepatic vascular occlusion with hanging maneuver was applied in Group 3 (n=24).The clamping period, operation time, bleeding volume, blood transfusion volume, postoperative recovery of liver function and postoperative complications were compared among three groups. RESULTS: The average times of clamping in Group 1 was 1.6 +/- 0.7, but only one clamping in Group 2 and 3. There were significant differences among three groups in bleeding volume as well. The postoperative serum ALT and total bilirubin (TBIL) in Group 2 and 3 were significantly lower than those of Group 1.5 patients died of liver failure after operation in Group 1. But liver failure or morbidity wasn't happened in Group 2 and 3. The rates of biliary leakage in Group 1 and 2 were more than that of Group 3. The hospitalization duration of Group 1 was significantly longer than those of Group 2 and 3. CONCLUSION: Hemihepatic vascular occlusion with hanging maneuver, which can reduce bleeding volume and enhance the recovery of liver function, is safe and practicable, especially for patients with liver cirrhosis.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/irrigação sanguínea , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Carcinoma Hepatocelular/fisiopatologia , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
Biomed Pharmacother ; 118: 109270, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401394

RESUMO

The landscape of cellular plasticity and sources with relevant niche signals in hepatocellular carcinoma is still obscure. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is involved in a variety of malignancies and overexpressed in hepatocellular carcinoma (HCC). We have investigated the role of TRPV1 in HCC from different angles by various experimental techniques, such as in vivo and in vitro experiments, and by bioinformatics analysis of data from genetic models induced by diethylnitrosamine (DEN), mice samples and human HCC samples. We find that TRPV1 knockout promotes to hepatocarcinogenesis and deconstructs the portal triad adjacent to tumor border that is contributed by originations of tumor initiating cells and biliary cells. Epithelial to mesenchymal transition (EMT) is involved and transcription factors Ovol2 and Zeb1 coordinated with Sox 10 drive gene expression in the event which is also confirmed by the expression of these proteins in human HCC samples. Treatment with TRPV1 agonist Capsaicin inhibits the growth of HCC cells in xenograft models. Our findings demonstrate that TRPV1 is a potential therapeutic target in human HCC and exerts effects on cellular plasticity with modulation of Ovol2, Zeb1 and Sox10.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Plasticidade Celular , Neoplasias Hepáticas/metabolismo , Canais de Cátion TRPV/metabolismo , Fatores de Transcrição/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Capsaicina/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/ultraestrutura , Linhagem Celular Tumoral , Plasticidade Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/ultraestrutura , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Hepatogastroenterology ; 55(85): 1153-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18795648

RESUMO

BACKGROUND/AIMS: For treatment of centrally located hepatocellular carcinoma (HCC), mesohepatectomy is a technically demanding procedure. The technique of an intrahepatic access to Glissonian pedicles achieves a safe inflow blood control of the liver segments to be resected and allows the anatomical removal of the tumor-bearing segment(s). No reports have mentioned the use of an intrahepatic access for mesohepatectomy in cirrhotic livers. METHODOLOGY: Seventeen consecutive patients underwent mesohepatectomy between January 1, 2005, and September 30, 2007. All these patients had hepatocellular carcinoma. The surgery was performed by making 3 small incisions around the hilar-plate, the gallbladder bed, and the round ligament. With a standardized method, the right anterior and left medial sheaths were reached by combining these incisions. RESULTS: Mesohepatectomy was feasible with the proposed technique in all patients. No patients experienced massive bleeding during the operation, and 14 patients did not require blood transfusion. Minor postoperative complications were observed in 8 patients and resolved with conservative management. No hospital mortality occurred. CONCLUSIONS: Intrahepatic Glissonian access for mesohepatectomy in cirrhotic patients is safe and effective. It may reduce intraoperative blood loss and the need for the Pringle maneuver.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Renais/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Hemostasia Cirúrgica , Humanos , Neoplasias Renais/patologia , Circulação Hepática , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Biomed Pharmacother ; 101: 910-919, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29635900

RESUMO

TRPV4 (transient receptor potential vanilloid 4), a member of the TRP superfamily, has been reported to correlate with several different forms of cancers. However, the role of TRPV4 in human hepatocellular carcinoma (HCC) remains unclear. The present study demonstrated that elevated expression of TRPV4 was shown in HCC tumor tissues when compared with paired non-tumoral livers both in protein and mRNA levels. Furthermore, the enhanced expression of TRPV4 was highly associated with histological grade (P = 0.036) and the number of tumors (P = 0.045). Pharmacological inhibition of TRPV4 channels in HCC cells with the specific antagonist HC-067047 suppressed cell proliferation, induced apoptosis and decreased the migration capability by attenuating the epithelial-mesenchymal transition (EMT) process in vitro. The p-ERK expression was apparently repressed after treatment with the TRPV4 antagonist, further blockade of the ERK pathway with U0126 could significantly aggravate HCC cells apoptosis. In NOD-SCID mouse xenograft models, intraperitoneal injection of HC-067047 could obviously suppress tumor growth and induce apoptosis in vivo. Together, our studies showed that the antitumor effects caused by TRPV4 channel inhibition in HCC cell lines might be attributed to the suppression of EMT process and inactivation of p-ERK which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 channel may be an option for HCC treatment.


Assuntos
Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Canais de Cátion TRPV/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade
19.
Hepatogastroenterology ; 54(77): 1311-4, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17708243

RESUMO

BACKGROUND/AIMS: Preservation of nontumorous liver parenchyma should be a priority in hepatic surgery in order to avoid the risk of life-threatening liver failure and maximize the possibility of repeat resection. METHODOLOGY: A tumor localized in segments VII, VIII and infiltrating the main trunk of the superior right hepatic vein usually indicates a need to perform a right hepatectomy. With the presence of a stout inferior right hepatic vein, bisegmentectomy VII, VIII can be carried out without the risk of hepatic congestion in the remaining segment VI. We retrospectively review our experience with this rare and challenging hepatic resection. RESULTS: In 23 of 715 patients with primary hepatocellular carcinoma, the tumor was localized in segments VII, VIII and involved with the superior right hepatic vein. Eleven underwent bisegmentectomy VII, VIII. Mean operative blood loss was estimated to be 300mL (200-1200mL), and only three patients required blood transfusions less than 2U each person. No patient had postoperative life-threatening liver failure and there was no postoperative mortality. All resection margins were negative. Median overall and disease-free survivals were 31 and 11 months, respectively, with five patients alive and disease-free. CONCLUSIONS: Bisegmentectomy VII and VIII is an oncologically radical but parenchyma-preserving liver resection. Though a rare hepatic resection, it can be performed safely with low morbidity and mortality in selected patients.


Assuntos
Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(6): 1085-8, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18182732

RESUMO

OBJECTIVE: To evaluate the highly-selective regional vascular exclusion in the risk hepatectomy for liver tumor. METHODS: Short hepatic veins were ligated and divided followed by the dissection, and isolation of the inflow and outflow vessels of the tumor-bearing lobe, which were completely devascularized after the occlusion of these vessels. The blood loss volume, postoperative recovering situation of the liver function and the incidence of complication were observed in 68 cases. RESULTS: Main hepatic veins were dissected and isolated exo-hepatically in 65 cases. In the other 3 cases, the main hepatic veins were blocked by Satin skin clamp applied longitudely along the inferior vena cava. Hepatic pedicle was routinely excluded.The amount of blood loss was from 400 to 1200 (600+/-200) mL and 26 (65%) cases didn't receive transfusion.There was no operative mortality and liver function failure. Surgical complications included subphrenic abscess in 2 cases and bile leakage in 2 cases, which were cured conservatively. CONCLUSION: Highly-selective regional exclusion of hepatic blood flow during the risk hepatectomy is safe and effective to prevent massive bleeding and to reduce the incidence of liver failure.


Assuntos
Hepatectomia/métodos , Veias Hepáticas/cirurgia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Adulto , Idoso , Feminino , Humanos , Fígado/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Cava Inferior/cirurgia
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