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1.
Liver Transpl ; 29(7): 698-710, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36825584

RESUMO

The safety of elderly living liver donors and recipient outcomes are always of concern. In the present study, the effects of age in 2 donor groups, a 60+years old group and a 50-59 years old group (referred to as the 60s and 50s donor groups, respectively), on living donor liver transplantation were compared regarding donor safety and recipient outcomes. We retrospectively identified 209 patients 50 years and above of age at 9 centers from 2005 to 2017 in Korea. The 60s donor group represented 10% (n=21) of donor patients. One case in each group was a left liver graft, respectively, and the others were right liver grafts. Postoperative complications were more common in the 60s donor group, but the proportion of Clavien-Dindo grade III in the 60s donor group did not differ from that in the 50s donor group. In-hospital mortality did not occur among donors, and donor mortality was not reported during the observation period. Postoperative total bilirubin and hospitalization in recipients of the 60s donor group were higher and longer than in recipients of the 50s donor group, respectively. Although the cumulative overall survival of the recipients in the 60s donor group was significantly lower than that of the 50s donor group, a difference was not observed in graft survival. Multivariate analysis showed that increased living liver donors age, the coexistence of HCC, and increased intraoperative blood loss during the recipient operation were important predisposing factors for patient death. Present study suggests that highly selected elderly living donors (≥60 y) can safely donate with similar recipient graft survival rates though the recipient overall patient survival is inferior compared to the 50s donor group.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Idoso , Pessoa de Meia-Idade , Criança , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , República da Coreia/epidemiologia , Sobrevivência de Enxerto , Resultado do Tratamento
2.
Hepatology ; 76(2): 345-356, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35108418

RESUMO

BACKGROUND AND AIMS: p21-activated kinase 4 (PAK4), an oncogenic protein, has emerged as a promising target for anticancer drug development. Its role in oxidative stress conditions, however, remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. APPROACH AND RESULTS: Hepatocyte- and myeloid-specific Pak4 knockout (KO) mice and their littermate controls were subjected to a partial hepatic I/R (HIR) injury. We manipulated the catalytic activity of PAK4, either through genetic engineering (gene knockout, overexpression of wild-type [WT] or dominant-negative kinase) or pharmacological inhibitor, coupled with a readout of nuclear factor erythroid 2-related factor 2 (Nrf2) activity, to test the potential function of PAK4 on HIR injury. PAK4 expression was markedly up-regulated in liver during HIR injury in mice and humans. Deletion of PAK4 in hepatocytes, but not in myeloid cells, ameliorated liver damages, as demonstrated in the decrease in hepatocellular necrosis and inflammatory responses. Conversely, the forced expression of WT PAK4 aggravated the pathological changes. PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. Nrf2 silencing in liver abolished the protective effects of PAK4 deficiency. A PAK4 inhibitor protected mice from HIR injury. CONCLUSIONS: PAK4 phosphorylates Nrf2 and suppresses its transcriptional activity. Genetic or pharmacological suppression of PAK4 alleviates HIR injury. Thus, PAK4 inhibition may represent a promising intervention against I/R-induced liver injury.


Assuntos
Hepatopatias , Traumatismo por Reperfusão , Quinases Ativadas por p21 , Animais , Apoptose , Humanos , Isquemia/metabolismo , Isquemia/patologia , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/prevenção & controle , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação , Traumatismo por Reperfusão/metabolismo , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo
3.
Ann Surg ; 271(5): 913-921, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30216223

RESUMO

OBJECTIVE: To identify optimal surgical methods and the risk factors for long-term survival in patients with hepatocellular carcinoma accompanied by macroscopic bile duct tumor thrombus (BDTT). SUMMARY BACKGROUND DATA: Prognoses of patients with hepatocellular carcinoma accompanied by BDTT have been known to be poor. There have been significant controversies regarding optimal surgical approaches and risk factors because of the low incidence and small number of cases in previous reports. METHODS: Records of 257 patients from 32 centers in Korea and Japan (1992-2014) were analyzed for overall survival and recurrence rate using the Cox proportional hazard model. RESULTS: Curative surgery was performed in 244 (94.9%) patients with an operative mortality of 5.1%. Overall survival and recurrence rate at 5 years was 43.6% and 74.2%, respectively. TNM Stage (P < 0.001) and the presence of fibrosis/cirrhosis (P = 0.002) were independent predictors of long-term survival in the Cox proportional hazards regression model. Both performing liver resection equal to or greater than hemihepatectomy and combined bile duct resection significantly increased overall survival [hazard ratio, HR = 0.61 (0.38-0.99); P = 0.044 and HR = 0.51 (0.31-0.84); P = 0.008, respectively] and decreased recurrence rate [HR = 0.59 (0.38-0.91); P = 0.018 and HR = 0.61 (0.42-0.89); P = 0.009, respectively]. CONCLUSIONS: Clinical outcomes were mostly influenced by tumor stage and underlying liver function, and the impact of BDTT to survival seemed less prominent than vascular invasion. Therefore, an aggressive surgical approach, including major liver resection combined with bile duct resection, to increase the chance of R0 resection is strongly recommended.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Trombose/patologia , Neoplasias dos Ductos Biliares/mortalidade , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Japão , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Trombose/mortalidade
4.
Pancreatology ; 20(5): 984-991, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32680728

RESUMO

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.


Assuntos
Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Stents , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/cirurgia , Fístula Pancreática/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , República da Coreia , Stents/efeitos adversos , Resultado do Tratamento
5.
J Korean Med Sci ; 35(6): e36, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32056398

RESUMO

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.


Assuntos
Antivirais , Vírus da Hepatite B , Hepatite B , Imunoglobulinas , Transplante de Fígado , Doadores Vivos , Antivirais/uso terapêutico , Estudos de Coortes , DNA Viral/sangue , Quimioterapia Combinada , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Imunoglobulinas/uso terapêutico , Sistema de Registros , República da Coreia
6.
HPB (Oxford) ; 22(8): 1139-1148, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31837945

RESUMO

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares , Estudos de Coortes , Humanos , República da Coreia/epidemiologia
7.
World J Surg ; 42(8): 2579-2591, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29340726

RESUMO

BACKGROUND: We developed a prognostic prediction model (PPM) using 4 factors for hepatic resection (HR) of large hepatic cellular carcinoma (HCC). Multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin, and tumor volume (TV) (ADV score) is a surrogate marker for post-resection prognosis. This study intended to validate the predictive power of 4-factor PPM and to develop new ADV score-based PPM. METHODS: A total of 526 patients who underwent HR for solitary HCC ≥ 8 cm were selected from 9 Korean institutions between 2008 and 2014. RESULTS: Median tumor diameter and TV were 11.0 cm and 398 mL, respectively. Tumor recurrence and patient survival rates were 53.0 and 78.4% at 1 year and 70.2 and 49.3% at 5 years, respectively. Independent risk factors for both tumor recurrence and patient survival included AFP ≥ 100 ng/mL, hypermetabolic FDG-positron emission tomography (PET), microvascular invasion and satellite nodules, which comprised 4 factors of the PPM. Five subgroups based on the number of involved risk factors exhibited significant differences in tumor recurrence and patient survival. ADV score cutoff was set at 7log (ADV7log) after cluster prognostic analysis. Patient grouping according to combination of ADV7log and FDG-PET findings (ADV7log-PET) exhibited significant differences in tumor recurrence and patient survival, comparable to those of the 4-factor PPM. CONCLUSIONS: Two PPMs using 4 risk factors and ADV7log-PET could reliably predict the risk of early HCC recurrence and long-term survival outcomes in patients who underwent HR for large HCC. We believe that these PPMs can guide surgical treatment for large HCCs from preoperative HR planning to post-resection follow-up.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos
8.
J Korean Med Sci ; 33(2): e10, 2018 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-29215819

RESUMO

BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. RESULTS: The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.


Assuntos
Desnutrição/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação Nutricional , Estado Nutricional , Prevalência , República da Coreia/epidemiologia , Fatores de Risco
9.
Ann Surg ; 266(6): 1062-1068, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27607098

RESUMO

OBJECTIVES: This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. BACKGROUND: Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. METHODS: Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. RESULTS: The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. CONCLUSION: A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Nomogramas , Neoplasias Pancreáticas/patologia , Lesões Pré-Cancerosas/patologia , Idoso , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Dilatação Patológica , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Ductos Pancreáticos/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos
10.
Liver Transpl ; 23(8): 999-1006, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28431203

RESUMO

Major concerns about donor safety cause controversy and limit the use of living donor liver transplantation to overcome organ shortages. The Korean Organ Transplantation Registry established a nationwide organ transplantation registration system in 2014. We reviewed the prospectively collected data of all 832 living liver donors who underwent procedures between April 2014 and December 2015. We allocated the donors to a left lobe group (n = 59) and a right lobe group (n = 773) and analyzed the relations between graft types and remaining liver volumes and complications (graded using the Clavien 5-tier grading system). The median follow-up was 19 months (range, 10-31 months). During the study period, 553 men and 279 women donated livers, and there were no deaths after living liver donation. The overall, biliary, and major complication (grade ≥ III) rates were 9.3%, 1.7%, and 1.9%, respectively. The graft types and remaining liver volume were associated with significantly different overall, biliary, and major complication rates. Of the 16 patients with major complications, 9 (56.3%) involved biliary complications (2 biliary strictures [12.5%] and 7 bile leakages [43.8%]). Among the 832 donors, the mean aspartate transaminase, alanine aminotransferase, and total bilirubin levels were 23.9 ± 8.1 IU/L, 20.9 ± 11.3 IU/L, and 0.8 ± 0.4 mg/dL, respectively, 6 months after liver donation. In conclusion, biliary complications were the most common types of major morbidity in living liver donors. Donor hepatectomy can be performed successfully with minimal and easily controlled complications. Our study shows that prospective, nationwide cohort data provide an important means of investigating the safety in living liver donation. Liver Transplantation 23 999-1006 2017 AASLD.


Assuntos
Hepatectomia/efeitos adversos , Transplante de Fígado/efeitos adversos , Doadores Vivos/estatística & dados numéricos , Segurança do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Colestase/sangue , Colestase/epidemiologia , Colestase/etiologia , Feminino , Seguimentos , Hepatectomia/métodos , Humanos , Fígado/cirurgia , Testes de Função Hepática , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , República da Coreia/epidemiologia , Coleta de Tecidos e Órgãos/estatística & dados numéricos , Adulto Jovem
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