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1.
Gut ; 67(11): 2006-2016, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29802174

RESUMO

OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Misturas Complexas/uso terapêutico , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante , Misturas Complexas/efeitos adversos , Feminino , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Análise de Sobrevida , Trametes , Resultado do Tratamento
2.
Med Sci Monit ; 24: 3720-3725, 2018 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-29860264

RESUMO

BACKGROUND The transient receptor potential melastatin 8 (TRPM8) was found to be expressed abnormally in a variety of tumors and is associated with unfavorable prognosis in human cancers. However, its clinical significance in pancreatic cancer (PC) is mostly unknown. MATERIAL AND METHODS qRT-PCR was performed to measure the expression of TRPM8 in 110 pairs of PC tissues and the adjacent non-cancerous tissues. The association of TRPM8 expression with the clinical characters of PC patients was analyzed using the chi-square test. Furthermore, the prognostic value of TRPM8 was determined with Kaplan-Meier survival curve and Cox regression analysis. RESULTS We found that the expression level of TRPM8 was significantly elevated in PC tissues compared to the non-cancerous controls (P<0.001). In addition, a close relationship was observed between elevated TRPM8 expression with large tumor size (P=0.001), advanced TNM (P=0.013), and distant metastasis (P=0.034). Survival analysis suggested that patients with high TRPM8 expression has worse OS (P=0.001) and DFS (P<0.001) than those with low TRPM8 expression. Moreover, TRPM8 was confirmed as a valuable prognostic biomarker for OS (HR=1.913; 95% CI: 1.020-3.589; P=0.043) or DFS (HR=2.374; 95% CI: 1.269-4.443; P=0.007) of PC patients. CONCLUSIONS This study shows that TRPM8 expression is significantly up-regulated in PC and it might be a useful prognostic factor for patients with PC.


Assuntos
Neoplasias Pancreáticas/metabolismo , Canais de Cátion TRPM/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Prognóstico , Análise de Sobrevida , Canais de Cátion TRPM/genética , Transcriptoma
4.
Hepatogastroenterology ; 62(138): 378-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25916067

RESUMO

The aim of the study is to identify the differentially expressed microRNAs (miRNAs) between hepatocellular carcinoma (HCC) samples and controls and provide new diagnostic potential miRNAs for HCC. The miRNAs expression profile data GSE20077 included 7 HCC samples, 1 HeLa sample and 3 controls. Differentially expressed miRNAs (DE-miRNAs) were identified by t-test and wilcox test. The miRNA with significantly differential expression was chosen for further analysis. Target genes for this miRNA were selected using TargetScan and miRbase database. STRING software was applied to construct the target genes interaction network and topology analysis was carried out to identify the hub gene in the network. And we identified the mechanism for affecting miRNA function. A total of 54 differentially expressed miRNAs were identified, in which there were 13 miRNAs published to be related to HCC. The differentially expressed hsa-miR-106b was chosen for further analysis and PTPRT (Receptor-type tyrosine-protein phosphatase T) was its potential target gene. The target genes interaction network was constructed among 33 genes, in which PTPRT was the hub gene. We got the conclusion that the differentially expressed hsa-miR-106b may play an important role in the development of HCC by regulating the expression of its potential target gene PT-PRT.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/genética , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Biologia Computacional , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Células HeLa , Humanos , Neoplasias Hepáticas/patologia , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Software
5.
Zhonghua Wai Ke Za Zhi ; 53(9): 676-9, 2015 Sep 01.
Artigo em Zh | MEDLINE | ID: mdl-26654146

RESUMO

OBJECTIVE: To investigate the method and effect of percutaneous nephroscopic necrosectomy (PNN) for post-operatively resident infection of severe acute pancreatitis (SAP). METHODS: Data of the 15 SAP patients with post-operatively resident infection treated by PNN from June 2008 to December 2014 in Chinese People's Liberation Army General Hospital were reviewed. Twelve of the patients underwent the laparotomy within 1 week, 1 in 3(rd) week, 1 in 4(th) week and the other one on the 127(th) day. All of the referrals firstly received (multi-)percutaneous catheter drainage (PCD), and then PNN operation according to the disease, followed by continuous irrigation-drainage. RESULTS: Eleven patients were healed after received only one PNN operation, 2 patients for twice, 1 for three times and 1 for four times. The average post-operative time of hospital stay was 66.2 days (10-223 days). The complications after operation contained colon fistula (n = 1), abdominal hemorrhage (n = 1), pancreatic pseudocyst (n = 1), severe pulmonary infection (n = 1). Three patients eventually died. CONCLUSIONS: Percutaneous nephroscopic necrosectomy is a minimally invasive approach which could prevent the complicated re-laparotomy operation, result in less complication. It is an ideal method for treating SAP patients with post-operatively resident infection.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Minimamente Invasivos , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/cirurgia , Complicações Pós-Operatórias/microbiologia , Drenagem , Humanos , Laparotomia , Tempo de Internação , Duração da Cirurgia , Reoperação
6.
Hepatogastroenterology ; 61(133): 1478-82, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25436328

RESUMO

UNLABELLED: BACKGROUND/AIMs: Pleiotrophin (PTN) have been demonstrated to play an important role in the development of human gastric cancer. However, the prognostic value remains unclear. The aim of this study was to investigate whether expression of PTN has prognostic relevance in human gastric cancer. METHODOLOGY: Immunohistochemistry was used to investigate the expression of PTN proteins in 178 patients with gastric cancer. The level of PTN mRNA in gastric cancer tissues and paratumor tissues were evaluated in 52 paired cases by quantitative real-time polymerase chainreaction(qRT-PCR). Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. RESULTS: The expression level of PTN in gastric cancer tissues was significantly higher (P<0.001) than those in paratumor tissues according to the immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of PTN was significantly associated with the tumor site (P=0.001), Lauren's classification (P<0.001),histologic differentiation(P=0.014),depth of invasion(P<0.001), TNM stage (P=0.003),and lymph node metastasis (P=0.002). Moreover, the Cox proportional- hazards regression analysis revealed that the increased expression of PTN was an independent prognostic factor for poor recurrence-free survival(RFS) and overall survival(OS)(both P<0.001). CONCLUSIONS: These findings indicated that the expression of PTN is significantly correlated with prognosis in gastric cancer patients, suggesting that the expression of PTN may be used as an independent prognostic marker.


Assuntos
Biomarcadores Tumorais/análise , Proteínas de Transporte/análise , Citocinas/análise , Neoplasias Gástricas/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Proteínas de Transporte/genética , Citocinas/genética , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto Jovem
7.
Hepatogastroenterology ; 61(136): 2215-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25699354

RESUMO

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most common malignancies, and liver metastasis is one of the major causes of death of CRC. This study aimed to compare the genetic difference between metachronous lesions (MC) and synchronous lesions (SC) and explore the molecular pathology of CRC metastasis. METHODOLOGY: Microarray expression profile data (GSE10961) including 8 MC and 10 SC was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the two groups were identified based on T test. Furthermore, GO enrichment analysis was performed for the down-regulated DEGs using DAVID. Finally, Classify validation of known CRC genes based on previous studies between MC and SC samples was conducted. RESULTS: Total of 36 DEGs including 35 down-regulated DEGs and 1 up-regulated DEGs were identified. The expressional differences of the 5 informative oncogenes: EGFr, PIK3R1, PTGS2 (COX-2), PTGS1 (COX1), and ALOX5AP between SC and MC were really tiny. CONCLUSIONS: Some DEGs, such as NFAT5, OLR1, ERAP2, HOXC6 and TWIST1 might play crucial roles in the regulation of CRC metastasis (both SC and MC) and by disrupting some pathways. However, our results indeed demand further research and experiment.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/patologia , Transcriptoma , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
8.
Hepatobiliary Pancreat Dis Int ; 13(5): 513-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25308362

RESUMO

BACKGROUND: Post-pancreaticoduodenectomy (PD) hemorrhage (PPH) is an uncommon but serious complication. This retrospective study analyzed the risk factors, managements and outcomes of the patients with PPH. METHODS: A total of 840 patients with PD between 2000 and 2010 were retrospectively analyzed. Among them, 73 patients had PPH: 19 patients had early PPH and 54 had late PPH. The assessment included the preoperative history of disease, pancreatic status and surgical techniques. Other postoperative complications were also evaluated. RESULTS: The incidence of PPH was 8.7% (73/840). There were no independent risk factors for early PPH. Male gender (OR=4.40, P=0.02), diameter of pancreatic duct (OR=0.64, P=0.01), end-to-side invagination pancreaticojejunostomy (OR=5.65, P=0.01), pancreatic fistula (OR=2.33, P=0.04) and intra-abdominal abscess (OR=12.19, P<0.01) were the independent risk factors for late PPH. Four patients with early PPH received conservative treatment and 12 were treated surgically. As for patients with late PPH, the success rate of medical therapy was 27.8% (15/54). Initial endoscopy was operated in 12 patients (22.2%), initial angiography in 19 (35.2%), and relaparotomy in 15 (27.8%). Eventually, PPH resulted in 19 deaths. The main causes of death were multiple organ failure, hemorrhagic shock, sepsis and uncontrolled rebleeding. CONCLUSIONS: Careful and ongoing observation of hemorrhagic signs, especially within the first 24 hours after PD or within the course of pancreatic fistula or intra-abdominal abscess, is recommended for patients with PD and a prompt management is necessary. Although endoscopy and angiography are the standard procedures for the management of PPH, surgical approach is still irreplaceable. Aggressive prevention of hemorrhagic shock and re-hemorrhage is the key to treat PPH.


Assuntos
Hemostase Endoscópica , Pancreaticoduodenectomia/efeitos adversos , Hemorragia Pós-Operatória/terapia , Abscesso Abdominal/complicações , Abscesso Abdominal/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Criança , Pré-Escolar , Procedimentos Endovasculares , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/anatomia & histologia , Fístula Pancreática/complicações , Fístula Pancreática/epidemiologia , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Semin Liver Dis ; 33(3): 189-203, 2013 Aug.
Artigo em Dinamarquês, Inglês | MEDLINE | ID: mdl-23943100

RESUMO

Continuous theoretical and technological progress in the face of increasing expectations for quality health care has transformed the surgical paradigm. The authors systematically review these historical trends and propose the novel paradigm of "precision surgery," featuring certainty-based practice to ensure the best result for each patient with multiobjective optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. The main characteristics of precision surgery may be summarized as determinacy, predictability, controllability, integration, standardization, and individualization. The strategy of precision in liver surgery is to seek a balance of maximizing the removal of the target lesion, while maximizing the functional liver remnant and minimizing surgical invasiveness. In this article, the authors demonstrate the application of precision approaches in specific settings in complex liver surgery. They propose that the concept of precision surgery should be considered for wider application in liver surgery and other fields as a step toward the ultimate goal of perfect surgery.


Assuntos
Hepatectomia , Hepatopatias/cirurgia , Técnicas de Apoio para a Decisão , Diagnóstico por Imagem/métodos , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hepatectomia/normas , Humanos , Valor Preditivo dos Testes , Resultado do Tratamento
10.
Cell Biochem Funct ; 31(8): 698-706, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23508530

RESUMO

Liver-directed gene therapy has become a promising treatment for many liver diseases. In this study, we constructed a multi-functional targeting molecule, which maintains targeting, endosome-escaping, and DNA-binding abilities for gene delivery. Two single oligonucleotide chains of Melittin (M) were synthesized. The full-length cDNA encoding anti-hepatic asialoglycoprotein receptor scFv C1 (C1) was purified from C1/pIT2. The GAL4 (G) gene was amplified from pSW50-Gal4 by polymerase chain reaction. M, C1 and G were inserted into plasmid pGC4C26H to product the recombinant plasmid pGC-C1MG. The fused gene C1MG was subsequently subcloned into plasmid pET32c to product the recombinant plasmid C1MG/pET32c and expressed in Escherichia coli BL21. The scFv-Mel-Gal4 triple fusion protein (C1MG) was purified with a Ni(2+) chelating HiTrap HP column. The fusion protein C1MG of roughly 64 kD was expressed in inclusion bodies; 4.5 mg/ml C1MG was prepared with Ni(2+) column purification. Western blot and immunohistochemistry showed the antigen-binding ability of C1MG to the cell surface of the liver-derived cell line and liver tissue slices. Hemolysis testing showed that C1MG maintained membrane-disrupting activity. DNA-binding capacity was substantiated by luciferase assay, suggesting that C1MG could deliver the DNA into cells efficiently on the basis of C1MG. Successful expression of C1MG was achieved in E. coli, and C1MG recombinant protein confers targeting, endosome-escaping and DNA-binding capacity, which makes it probable to further study its liver-specific DNA delivery efficacy in vivo.


Assuntos
Proteínas de Ligação a DNA/genética , DNA/metabolismo , Escherichia coli/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Anticorpos de Cadeia Única/genética , Fatores de Transcrição/genética , Animais , Receptor de Asialoglicoproteína/genética , Receptor de Asialoglicoproteína/metabolismo , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , DNA/genética , Proteínas de Ligação a DNA/metabolismo , Portadores de Fármacos , Escherichia coli/metabolismo , Células Hep G2 , Humanos , Fígado/citologia , Fígado/metabolismo , Especificidade de Órgãos , Plasmídeos/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas de Saccharomyces cerevisiae/metabolismo , Anticorpos de Cadeia Única/metabolismo , Fatores de Transcrição/metabolismo
11.
World J Surg Oncol ; 11: 30, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23375073

RESUMO

We report a case of papillary carcinoma of the duodenum combined with right renal carcinoma. A 58-year-old man underwent a physical examination that revealed intrahepatic and extrahepatic bile duct dilatation on B ultrasound. Intrahepatic bile duct dilatation could be seen on magnetic resonance imaging (MRI), but the head of the pancreas and distal bile duct showed no tumor signals, which led to a diagnosis of periampullary carcinoma and right renal carcinoma. Considering the trauma of pancreaticoduodenectomy combined with renal resection operation is greater, we carried out the laparoscopic right renal radical resection first, and then a pylorus-preserving pancreaticoduodenectomy was performed. However, postoperative intra-abdominal infections and bleeding occurred; our patient improved after vascular interventional microcoil embolization for the treatment of hemostasis. The second operation for celiac necrotic tissue elimination, jejunal fistulization and peritoneal lavage and drainage was performed 14 days latter. Our patient improved gradually and was discharged on the 58th postoperative day. There has been no tumor recurrence after a follow-up of 26 months.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/patologia , Neoplasias Renais/patologia , Neoplasias Primárias Múltiplas/patologia , Carcinoma Papilar/cirurgia , Carcinoma de Células Renais/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/cirurgia , Pancreaticoduodenectomia , Prognóstico , Tomografia Computadorizada por Raios X
12.
Hepatobiliary Pancreat Dis Int ; 12(3): 244-50, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23742768

RESUMO

BACKGROUND: Liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy. Taking advantage of modern technologies, liver surgery is stepping into an age of precise liver resection. This review aimed to analyze the comprehensive application of modern technologies in precise liver resection. DATA SOURCE: PubMed search was carried out for English-language articles relevant to precise liver resection, liver anatomy, hepatic blood inflow blockage, parenchyma transection, and down-staging treatment. RESULTS: The 3D image system can imitate the liver operation procedures, conduct risk assessment, help to identify the operation feasibility and confirm the operation scheme. In addition, some techniques including puncture and injection of methylene blue into the target Glisson sheath help to precisely determine the resection. Alternative methods such as Pringle maneuver are helpful for hepatic blood inflow blockage in precise liver resection. Moreover, the use of exquisite equipment for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator, ultrasonic scalpel, Ligasure and Tissue Link is also helpful to reduce hemorrhage in liver resection, or even operate exsanguinous liver resection without blocking hepatic blood flow. Furthermore, various down-staging therapies including transcatheter arterial chemoembolization and radio-frequency ablation were appropriate for unresectable cancer, which reverse the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation is possible. CONCLUSIONS: Modern technologies mentioned in this paper are the key tool for achieving precise liver resection and can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. In addition, large randomized trials are needed to evaluate the usefulness of these technologies in patients with hepatocellular carcinoma who have undergone precise liver resection.


Assuntos
Hepatectomia/métodos , Robótica , Cirurgia Assistida por Computador , Diagnóstico por Imagem/métodos , Hepatectomia/efeitos adversos , Humanos , Imageamento Tridimensional , Complicações Pós-Operatórias/prevenção & controle , Valor Preditivo dos Testes , Resultado do Tratamento
13.
Zhonghua Wai Ke Za Zhi ; 51(7): 592-5, 2013 Jul.
Artigo em Zh | MEDLINE | ID: mdl-24256582

RESUMO

OBJECTIVE: To evaluate the effectiveness of dynamic SPECT (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy on the assessment of reserve function of cirrhosis liver. METHODS: From January 2010 to December 2011, 55 patients with cirrhosis liver were enrolled in this study. The case numbers of male and female were 43 and 12 respectively and the age was (51 ± 9) years (ranging from 35 to 69 years). After routine biochemistry test, CT scan and (99m)Tc-GSA dynamic SPECT scan were performed in turn using a juxtaposed SPECT/CT system. Then the morphologic volume of liver parenchyma (MLV), functional liver volume (FLV) and the hepatic cell absorption rate constant (GSA-K) were calculated. The correlations between GSA-K and routine biochemistry test, Child-Pugh score, indocyanine green clearance rate (ICG-K) were analyzed. The patients were further divided into 3 groups according to whether there was occlusion or stenosis in the main branch of left portal vein (group 1, n = 5), right portal vein (group 2, n = 13) or not (group 3, n = 37) and the regional hepatic functions index of the 3 groups were compared. RESULTS: The value of FLV of the whole, left and right liver was (594 ± 152) ml, (244 ± 119) ml and (356 ± 171) ml, respectively. There were correlations between GSA-K and total bilirubin, prothrombintime, Child-Pugh score and ICG-K (r = -0.730--0.298, P < 0.05). The FLV and MLV ratios of involved hemiliver to uninvolved hemiliver were 0.09 ± 0.06 and 0.30 ± 0.14 in group 1, 0.57 ± 0.43 and 1.08 ± 0.63 in group 2, 0.71 ± 0.30 and 0.71 ± 0.48 in group 3. The difference in MLV-FLV ratio was signifcant between group 1 and group 3, between group 2 and group 3 (P = 0.000). CONCLUSIONS: The dynamic SPCECT (99m)Tc-GSA scintigraphy can not only assess the whole liver function of cirrhosis liver effectively, but also evaluate the variation of regional liver function accurately.


Assuntos
Cirrose Hepática/fisiopatologia , Fígado/fisiopatologia , Agregado de Albumina Marcado com Tecnécio Tc 99m/metabolismo , Pentetato de Tecnécio Tc 99m/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade
14.
J Immunother Cancer ; 11(9)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37730273

RESUMO

BACKGROUND: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. METHODS: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. RESULTS: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. CONCLUSION: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023914.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Linfócitos T CD8-Positivos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Microambiente Tumoral
15.
Tohoku J Exp Med ; 227(4): 269-80, 2012 08.
Artigo em Inglês | MEDLINE | ID: mdl-22820835

RESUMO

Hepatocellular carcinoma (HCC) is the most common liver tumor in Asian countries, and hepatectomy is currently regarded as the optimal curative treatment for HCC; however, the postoperative outcome remains unsatisfactory. Aiming at further clarification of prognostic factors after hepatectomy, we adopted a detailed stratification on survival periods. A total of 428 HCC patients undergoing curative hepatectomy were firstly divided into two groups using 2-year survival as cutoff point. Multivariate analysis showed that tumor-related factors, including vascular invasion (P < 0.001), high Edmondson grade (P < 0.001), large tumor size (P < 0.001) and high serum alpha-fetoprotein level (P = 0.001), were significant determinants for early death within 2 years, while postoperative transarterial chemoembolization (TACE) was demonstrated a protective factor (P = 0.013). Then the 281 patients with survival > 2 years were divided into two subgroups according to survival or death during follow-up to examine the late death related factors. We found that high serum γ-glutamyl transpeptidase (GGT), indicating severity of underlying liver disease, was significantly linked to death in this stage (P = 0.006). In further comparison of survival rates between subgroups stratified by early- and late-death indictors, we found the long-term outcomes of patients with high serum GGT were poor, regardless of the factors related with primary tumor. Furthermore, postoperative TACE decreased late death rate of patients with high GGT levels. In conclusion, despite the overwhelmed effects of primary tumor in the early stage after hepatectomy, postoperative TACE is beneficial for HCC patients with poor liver status.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , gama-Glutamiltransferase/sangue , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/mortalidade , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Pós-Operatórios , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 34(1): 14-8, 2012 Feb.
Artigo em Zh | MEDLINE | ID: mdl-22737713

RESUMO

OBJECTIVE: To explore the effects of different hepatic inflow occlusion methods on liver regeneration in rats after partial hepatectomy (PH). METHODS: Male Wistar-Furth rats were randomly assigned to three groups: control group, underwent 68% hepatectomy alone; occlusion of portal triad (OPT) group, subjected to occlusion of portal triad under portal blood bypass; and occlusion of portal vein (OPV) group, subjected to occlusion of portal vein under portal blood bypass. Blood flow was occluded for 20, 30, and 40 minutes before 68% hepatectomy. According to the 7-day survival of each group, a same occlusion time T was set. Each group was divided into two subgroups (n = 8), in which animals were killed 3 and 7 days later. Liver regeneration was calculated as a percent of initial liver weight. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) and Ki-67 was performed to quantify proliferating cells. In addition, functional liver volume represented by 99Tc(m)-GSA radioactivity was assessed. RESULTS: The safe tolerance limit time was 30 minutes for OPT group and 40 minutes for OPV group. At 3 days after PH, no significant difference was observed in the regeneration rate of each group (P > 0.05). However, liver radioactive activity, PCNA labeling index, and Ki-67 index of OPV group was significantly higher than those of OPT group (P < 0.05); the latter were similar to those of control group (P > 0.05). At 7 days after PH, no significant difference was observed in all indexes among three groups (P > 0.05). CONCLUSION: Compared with Pringle maneuver, preserving the hepatic artery flow during portal triad blood inflow occlusion can promote remnant liver regeneration early after PH.


Assuntos
Hepatectomia/métodos , Regeneração Hepática/fisiologia , Animais , Fígado/irrigação sanguínea , Fígado/cirurgia , Masculino , Período Pós-Operatório , Ratos , Ratos Wistar
17.
Zhonghua Wai Ke Za Zhi ; 50(6): 502-4, 2012 Jun.
Artigo em Zh | MEDLINE | ID: mdl-22943942

RESUMO

OBJECTIVE: To evaluate the role of anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi by application of persistent methylene blue dyeing method. METHODS: From January 2009 to February 2011, 11 hepatocellular carcinoma patients with bile duct tumor thrombi underwent anatomic hepatectomy with removal of the biliary tumor thrombus. There were 10 male and 1 female patients. The average age was 49 years (ranging from 31 to 67 years). The initial symptom of 9 out of the 11 patients was jaundice. After anatomy and ligation of Glissonean pedicle of pre-resection segment, methylene blue was injected into its far-end portal vein in order to dye the segment. RESULTS: Persistent methylene blue dyeing method was successful in all patients. Primary foci were found in all patients. Hepatectomy were performed, including 4 patients of segmentectomy, 3 patients of subsegmentectomy, 2 patients of hemihepatectomy, and 2 patients of hepatic sectionectomy. The mean operation time and blood loss was 137 minutes and 246 ml respectively. Severe complications such as liver function failure and sub-diaphragm abscess was avoided in all patients. No perioperative death. Post-operation radiotherapy was performed on 2 patients . Over a mean follow-up time of 14.6 months, liver cancer recurrence occurred in 2 patients, abdomen seeding metastasis in 1 patient, bile duct tumor thrombi recurrence in 1 case, and 2 patients died. CONCLUSIONS: Anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi by application of persistent methylene blue dyeing method can make resection more precise and improve curative effect.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Azul de Metileno , Coloração e Rotulagem , Adulto , Idoso , Neoplasias dos Ductos Biliares/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Zhonghua Yi Xue Za Zhi ; 89(48): 3409-12, 2009 Dec 29.
Artigo em Zh | MEDLINE | ID: mdl-20223115

RESUMO

OBJECTIVE: To investigate the determinants of long-term survival for ampulla of Vater carcinoma treated by pancreaticoduodenectomy. METHODS: A total of 77 patients with ampulla of Vater carcinoma undergoing pancreaticoduodenectomy were reviewed. Kaplan-Meier method was used to analyze the survival rate. Independent t test was used for statistical comparison and COX regression model for multivariate analysis. RESULTS: No patient died as a result of surgery. The overall 5-year survival was 40.7%. Univariate analysis showed that perioperative serum carcinoembryonic antigen (CEA) level (P = 0.012), tumor invasion depth (P = 0.000), UICC stage (P = 0.000) and tumor size (P = 0.001) were significant prognostic factors of ampulla of Vater carcinoma; in multivariate analysis, only the tumor size (P = 0.000) was an independent prognostic factor of ampulla of Vater carcinoma. CONCLUSION: Pancreaticoduodenectomy is associated with significant survival. Tumor size is the most important influencing factor of outcome after pancreaticoduodenectomy; in addition, perioperative serum CEA level, tumor invasion depth and UICC stage may also influence the survival rate, there exists a need for further follow-up studies.


Assuntos
Ampola Hepatopancreática/cirurgia , Carcinoma/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Pancreaticoduodenectomia/mortalidade , Adulto , Idoso , Carcinoma/mortalidade , Neoplasias do Ducto Colédoco/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida
20.
Zhonghua Wai Ke Za Zhi ; 47(15): 1138-41, 2009 Aug 01.
Artigo em Zh | MEDLINE | ID: mdl-20021902

RESUMO

OBJECTIVE: To summarize the methods, safety and efficiency of surgical resection for hilar cholangiocarcinoma. METHODS: The clinical and follow-up data of 48 patients with hilar cholangiocarcinoma underwent surgical resection from January 2003 to December 2007 were analyzed retrospectively. There were 26 male and 22 female, aged from 38 to 72 years old with a mean of 63.6 years old. RESULTS: Perioperative management including percutaneous transhepatic biliary drainage applied in 19 cases and portal vein embolization applied in 2 cases. Eight patients were treated with extrahepatic bile duct resection with or without parital hepatic segment II resection, 10 cases with perihilar hepatic resection (segment IVB, partial V, partial VIII, I), 28 cases with extended hemihepatectomy and 2 cases with central hepatic resection (segment IVB, V, VIII, I). R0 resection rate was 89.5% and the operative mortality was 2.1%. The 1-, 3- and 5-year survival rate were 93.5%, 51.8% and 36.5%, respectively. Patients undergoing extended hepatic resection survived significantly longer than those undergoing partial hepatic resection (P = 0.034). CONCLUSIONS: Extended hepatic resection for hilar cholangiocarcinoma offers good outcomes with an acceptable mortality rate.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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