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1.
Hepatol Res ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414147

RESUMO

AIM: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living-donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients. METHOD: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT. RESULTS: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles. CONCLUSION: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT.

2.
Surg Today ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38055105

RESUMO

Some patients with refractory esophagogastric varices require surgery, such as gastric devascularization and splenectomy (Hassab's procedure). However, these patients are at risk of perioperative morbidities when undergoing devascularization to develop collateral vessels. We performed a more simplified procedure, splenectomy, and en bloc gastropancreatic fold division (GPFD) with hand-assisted laparoscopic surgery. Four patients with refractory esophagogastric varices and portal hypertension underwent splenectomy and GPFD. We reviewed patients' perioperative laboratory and morphological data, operative variables, and postoperative outcomes. Esophagogastric varices improved in 3 (75%) of the 4 patients. In one patient, esophageal varices (F1RC0) were observed 3 years after surgery, but they required no treatment and only received follow-up. Treatment with splenectomy and GPFD is not only less invasive than Hassab's procedure but also provides effective outcomes for refractory esophagogastric varices.

3.
Semin Liver Dis ; 42(4): 413-422, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36044927

RESUMO

Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)-derived liver cells are being utilized to study liver disease and to identify and test potential therapeutics. Moreover, bioengineered livers containing pig hepatocytes and endothelial cells have been shown to function and survive after transplantation into pig models of liver failure, providing preclinical evidence toward future clinical applications. Finally, bioengineered livers containing human iPSC-derived liver cells have been shown to function and survive after transplantation in rodents but require considerable optimization and testing prior to clinical use. In conclusion, bioengineered livers have emerged as a suitable tool for modeling liver diseases and as a promising alternative graft for clinical transplantation. The integration of novel technologies and techniques for the assembly and analysis of bioengineered livers will undoubtedly expand future applications in basic research and clinical transplantation.


Assuntos
Células-Tronco Pluripotentes Induzidas , Hepatopatias , Falência Hepática , Humanos , Suínos , Animais , Células Endoteliais , Hepatócitos , Fígado/fisiologia , Hepatopatias/cirurgia
4.
Cancer Sci ; 113(1): 156-169, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34704338

RESUMO

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2-associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail-anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR-Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6-mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.


Assuntos
Neoplasias Colorretais/patologia , Chaperonas Moleculares/genética , Regulação para Cima , Acetilação , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Masculino , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Proteína Supressora de Tumor p53/metabolismo
5.
Transpl Int ; 35: 10723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568139

RESUMO

The recipient muscle status is closely associated with postoperative poor survival in recipients of living donor liver transplantation (LDLT). However, it is uncertain whether LDLT donor muscle quality and quantity affect graft quality. Hence, we analyzed the correlation between donor muscle status and graft function. We measured the skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) of 380 LDLT donors. We examined the correlation between donor SMI or IMAC and graft mortality, the occurrence rates of small-for-size graft (SFSG) syndrome, and 6-month graft survival rates. The donor SMI had no effect on the occurrence of SFSG syndrome and graft survival, while a high IMAC in both male and female donors was significantly correlated with the rate of SFSG syndrome [high vs low: (male donors) 15.8% vs. 2.5%, p = 0.0003; (female donors) 12.8% vs. 3.1%, p = 0.0234] and 6-month graft survival rates [(male donors) 87.7% vs 95.9%, p = 0.02; (female donors) 83.0% vs. 99.0%, p < 0.0001]. Multivariate analysis revealed that a high donor IMAC (HR; 5.42, CI; 2.13-13.8, p = 0.0004) was an independent risk factor for 6-month graft survival, and the donor IMAC is useful for donor selection for high-risk recipients.


Assuntos
Transplante de Fígado , Masculino , Humanos , Feminino , Doadores Vivos , Estudos Retrospectivos , Músculo Esquelético , Fatores de Risco , Sobrevivência de Enxerto , Resultado do Tratamento
6.
J Hepatol ; 74(2): 372-379, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32827564

RESUMO

BACKGROUND & AIMS: Small-for-size graft (SFSG) syndrome is a major cause of graft loss after living donor liver transplantation (LDLT). Splenectomy (Spx) is an option to prevent this catastrophic complication, but its effect remains controversial. Herein, we aimed to elucidate the effect of simultaneous Spx on graft function and long-term outcomes after LDLT. METHODS: Three hundred and twenty patients were divided into 2 groups: those undergoing (n = 258) and those not undergoing (n = 62) simultaneous Spx. To overcome selection bias, propensity score matching (PSM) was performed (n = 50 in each group). RESULTS: Before PSM, recipients undergoing simultaneous Spx showed better graft function on post-operative day (POD) 7 and 14, as well as lower sepsis frequency within 6 months after LDLT and better graft survival rates compared to those not undergoing Spx. After PSM, compared to patients not undergoing Spx, those undergoing Spx had a lower frequency of early graft dysfunction on POD 7 (p = 0.04); a lower frequency of SFSG syndrome (p = 0.01), lower serum total bilirubin levels (p = 0.001), and lower international normalized ratio (p = 0.004) on POD 14; lower sepsis frequency within 6 months after LDLT (p = 0.02), and better graft survival rates (p = 0.04). Univariate analysis revealed that not undergoing Spx (hazard ratio 3.06; 95% CI 1.07-11.0; p = 0.037) was the only risk factor for graft loss after LDLT. CONCLUSIONS: Simultaneous Spx may prevent SFSG syndrome and is a predictive factor for graft survival after LDLT. Simultaneous Spx is recommended when a small graft (≤35% of standard liver weight) is predicted preoperatively, or for patients with portal hypertension or high portal pressure (above 20 mmHg) after reperfusion in LDLT. LAY SUMMARY: Living donor liver transplantation (LDLT) for patients with acute or chronic liver failure is an alternative to overcome the deceased donor shortage. The potential mismatch between graft and body size is a problem that needs to be solved for LDLT recipients. Herein, we evaluated the impact of simultaneous splenectomy and showed that it was associated with favorable outcomes in patients undergoing LDLT.


Assuntos
Sobrevivência de Enxerto , Transplante de Fígado , Fígado , Doadores Vivos , Complicações Pós-Operatórias , Esplenectomia/métodos , Feminino , Humanos , Japão/epidemiologia , Fígado/patologia , Fígado/cirurgia , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Risco Ajustado/métodos , Tolerância ao Transplante
7.
Hepatology ; 72(6): 1987-1999, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32112577

RESUMO

BACKGROUND AND AIMS: We investigated the prognostic value of programmed death ligand 1 (PD-L1) expression, tumor-infiltrating CD8-positive T-cell status, and their combination in hepatocellular carcinoma (HCC). Their association with PD-L1 expression and vascular formation was further explored. APPROACH AND RESULTS: Using a database of 387 patients who underwent hepatic resection for HCC, immunohistochemical staining of PD-L1, CD8, and CD34 was performed. Additionally, we undertook an enzyme-linked immunosorbent assay for soluble PD-L1. Compared with patients with HCC and PD-L1-negative expression (n = 311), patients with HCC and PD-L1-positive expression (n = 76) showed significantly worse overall survival (OS; multivariate hazard ratio, 2.502; 95% confidence interval [CI], 1.716-3.649; P < 0.0001). The presence of tumor-infiltrating CD8-positive T cells was significantly correlated with longer OS (multivariate hazard ratio, 0.383; 95% CI, 0.274-0.537; P < 0.0001). Stratification based on PD-L1 expression in cancer cells and tumor-infiltrating CD8-positive T-cell status was also significantly associated with OS (log-rank, P < 0.0001). HCC with PD-L1-positive expression was significantly correlated with positivity for vessels that encapsulated tumor clusters. Serum PD-L1 levels were significantly higher in the group of patients who had PD-L1-positive expression than in the group of patients who had PD-L1-negative expression (P = 0.0158). CONCLUSIONS: PD-L1 expression in cancer cells was associated with a poor clinical outcome and vascular formation in patients with HCC. Additionally, the combination of PD-L1 expression with tumor-infiltrating CD8-positive T-cell status enabled further classification of patients based on their clinical outcome. Thus, PD-L1 expression in cancer cells and tumor-infiltrating CD8-positive T-cell status might serve as predictive tissue biomarkers.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Neovascularização Patológica/imunologia , Microambiente Tumoral/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/imunologia , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/cirurgia , Linfócitos do Interstício Tumoral/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/imunologia , Neovascularização Patológica/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Langenbecks Arch Surg ; 406(3): 773-779, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33595705

RESUMO

PURPOSE: Systemic inflammation score (SIS) is a novel prognostic score (0, 1, or 2) for various cancers, based on preoperative serum albumin level and lymphocyte-to-monocyte ratio (LMR); modified SIS (mSIS) uses a different LMR cutoff value and was thought to be a more accurate predictor for cancer prognosis. Here, we assessed the prognostic value of SIS and mSIS in patients who receive hepatic resection for hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated SIS and mSIS of 314 patients after hepatic resection for HCC, against their clinicopathological factors and outcomes, using receiver operating characteristics (ROC) analysis over time. RESULTS: Among patients with preoperative SIS 2, significantly more HCC specimens were poorly differentiated (P = 0.0281), larger (P = 0.0006), and had more microscopic vascular invasion (P = 0.0136) than the SIS 0-1 group; the mSIS 2 group also had significantly larger tumors (P = 0.0039) than the mSIS 0-1 group. In ROC analysis, SIS was a better predictor of overall survival (OS) and recurrence-free survival (RFS) than mSIS. The SIS 2 group had shorter OS (P = 0.0015) and RFS (P = 0.0065) than other patients. In multivariate analysis, SIS 2 was an independent risk factor for shorter OS (hazard ratio (HR) 1.53, P = 0.0497) and RFS (HR 1.58, P = 0.0053). CONCLUSION: SIS is superior to mSIS in predicting prognosis of patients with HCC. mSIS is not a great predictor of prognosis in resected HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Humanos , Inflamação , Neoplasias Hepáticas/cirurgia , Prognóstico , Estudos Retrospectivos
9.
Ann Surg Oncol ; 27(9): 3344-3353, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32246316

RESUMO

BACKGROUND: The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown. Our aim is to clarify the long-term outcomes in patients with this finding. METHODS: We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center. We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. RESULTS: There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively). There was no significant difference between these two groups after propensity score matching. Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not. There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). CONCLUSIONS: Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy. Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fígado , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Feminino , Gadolínio DTPA , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Pancreatology ; 20(6): 1175-1182, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32741713

RESUMO

BACKGROUND/OBJECTIVES: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. RESULTS: The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. CONCLUSIONS: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , DNA Glicosilases/biossíntese , Mitocôndrias/metabolismo , Neoplasias Pancreáticas/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Antígeno CA-19-9 , Carcinoma Ductal Pancreático/cirurgia , Núcleo Celular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
11.
Clin Transplant ; 34(6): e13850, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32150767

RESUMO

INTRODUCTION: The aim of this study was to clarify the impact of middle hepatic artery reconstruction on the outcomes of duct-to-duct biliary anastomosis after living donor liver transplantation (LDLT) using the left lobe. MATERIALS AND METHODS: Among 258 patients who underwent LDLT using the left lobe, 216 patients who underwent hepatic artery reconstruction and one hepatic duct reconstruction with duct-to-duct interrupted anastomosis were divided into three groups: Group A (n = 123), one arterial stump with left hepatic artery reconstruction; Group B (n = 32), two arterial stumps with only left hepatic artery reconstruction; and Group C (n = 61), two arterial stumps with reconstruction of the left and middle hepatic arteries. The outcomes after LDLT were compared among the three groups. RESULTS: No hepatic artery complications occurred. Group B had a significantly greater incidence of anastomotic biliary stricture than Group C. A multivariate analysis with Cox regression revealed that being in Group B was the only significant independent risk factor for postoperative anastomotic biliary stricture after LDLT. CONCLUSIONS: Middle and left hepatic artery reconstruction is safe in LDLT and may prevent biliary stricture caused by dual hepatic artery reconstruction when the graft has left and middle hepatic artery stumps.


Assuntos
Transplante de Fígado , Anastomose Cirúrgica , Artéria Hepática/cirurgia , Humanos , Fígado/cirurgia , Doadores Vivos , Complicações Pós-Operatórias
12.
Hepatol Res ; 50(1): 101-109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31692173

RESUMO

AIM: There is increasing evidence that inflammation-based prognostic scores are stage-independent predictors of poor outcome in patients with hepatocellular carcinoma (HCC). However, these findings were observed in a small-sized study comparing the prognostic value of these scores for patients after curative resection for HCC. METHODS: We retrospectively analyzed 717 consecutive patients with HCC who underwent curative liver resection at Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital. Clinicopathological variables including preoperative inflammation-based prognostic scores, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Controlling Nutritional Status score, prognostic nutritional index (PNI), and Glasgow Prognostic Score were analyzed. The prognostic value of these scores was compared by the time-dependent receiver operating characteristic curve analyses. RESULTS: The integrate area under the curve of PNI, Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Glasgow Prognostic Score were 0.6751, 0.6435, 0.5845, 0.5276, and 0.5351 for overall survival (OS), respectively, and 0.5955, 0.5694, 0.4692, 0.4873, and 0.5272 for disease-free survival, respectively. Multivariate analyses for prognosis factor in HCC patients showed that PNI was an independent predictor of both OS (HR 0.91, P < 0.001) and disease-free survival (HR 0.94, P < 0.001). When the patients were divided into high and low PNI groups, the patients in the low PNI group had significant poorer OS (P < 0.001) and disease-free survival (P < 0.001), even after background factors were matched between these two groups. CONCLUSIONS: PNI is superior to Controlling Nutritional Status score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or Glasgow Prognostic Score as a predictor of OS and recurrence-free survival in patients with HCC who underwent curative hepatic resection.

13.
World J Surg ; 44(1): 258-267, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31624895

RESUMO

BACKGROUND: Osteopenia, loss of bone mineral density (BMD), was recently identified to be independently associated with early marker of deconditioning that precedes sarcopenia in patients with hepatocellular carcinoma (HCC). The aim of this study was to clarify the impact of osteopenia as the risk factor for mortality after living donor liver transplantation (LDLT) compared with already-reported biological markers. METHODS: Data were collected retrospectively for all consecutive patients who underwent LDLT for HCC at our institution between January 1998 and December 2015. BMD was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Data related to clinicopathological parameters and prognosis were analyzed. RESULTS: The median value of BMD was 163.6 Hounsfield units and osteopenia was identified in 103 (53.4%) of the 193 recipients, according to the age-specific formula. In addition to the other tumor burdens, such as tumor numbers ≥5 (HR 2.521, P = 0.027), DCP levels >200 mAU/mL (HR 2.678, P = 0.006), and neutrophil-to-lymphocyte ratio ≥3.01 (HR 2.068, P = 0.025), osteopenia (HR 2.106, P = 0.024) was independent risk factor for mortality by multivariate analysis. Overall survival of the patients who met the two risk factors and more was significantly lower than the others (HR 5.382, P < 0.001). Besides, the calibration plot for the 5-year overall survival using nomogram was predicted very well (C-index 0.746). CONCLUSIONS: Preoperative osteopenia was independently associated with post-LDLT mortality among patients with HCC. Moreover, risk score and nomogram with calibration curve were developed to confirm the clinical usefulness of osteopenia for post-LDLT patients.


Assuntos
Doenças Ósseas Metabólicas/complicações , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Doadores Vivos , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Estudos Retrospectivos
14.
Pathol Int ; 70(8): 533-541, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32419286

RESUMO

Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/metabolismo , Carcinoma Hepatocelular , DNA Glicosilases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Desoxiguanosina/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
15.
HPB (Oxford) ; 22(4): 511-520, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31561946

RESUMO

BACKGROUND: Metabolic syndrome (MS) is the most common long-term complication after liver transplantation, and it has been increasing in incidence. The aim of this study was to clarify the risk factors for each MS component -hypertension, diabetes mellitus, and dyslipidemia-after living-donor liver transplantation (LDLT), including characteristics of living-donors. METHODS: Data related to clinicopathological parameters including MS components in 461 consecutive patients who underwent LDLT were analyzed retrospectively. RESULTS: Prevalence of all MS components (hypertension, diabetes mellitus, and dyslipidemia) increased from 9.3%, 16.5%, and 7.2% before LDLT to 44.9%, 45.3%, and 50.8% after LDLT, respectively. By multivariate logistic regression analysis, the three factors, cyclosporine use (OR 2.086, P = 0.001), recipient age (OR 1.036, P = 0.001), and BMI (OR 1.072, P = 0.026) were independent predictors for post-LDLT hypertension. Next, the three factors, male recipient (OR 2.471, P < 0.001), recipient age (OR 1.039, P = 0.002), and donor BMI (OR 1.124, P = 0.012) were independent for post-LDLT diabetes mellitus. The four factors, cyclosporine use (OR 2.015, P = 0.001), prolonged prednisolone use (OR 1.928, P = 0.002), recipient age (OR 1.019, P = 0.037), and GRWR (OR 0.316, P = 0.037) were independent for post-LDLT dyslipidemia as well. CONCLUSIONS: Not only recipient-related factors but also donor-related factors were independently associated with each targeted post-LDLT MS component.


Assuntos
Complicações do Diabetes/complicações , Dislipidemias/complicações , Hipertensão/complicações , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
16.
World J Surg ; 42(4): 1120-1128, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28920178

RESUMO

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) with portal hypertension (PH) is very poor. Splenomegaly is considered important evidence of PH. Our aim was to clarify the prognostic value of splenic volume (SV) and the effect of splenectomy on the prognosis of HCC within the Milan criteria after curative hepatectomy. METHODS: In this single-center retrospective study, we reviewed 160 patients with HCC that met the Milan criteria, including 138 who had undergone hepatectomy and 22 who had undergone hepatectomy and splenectomy between July 2004 and December 2010. SV was measured by three-dimensional computed tomography and patients allocated to three groups (high SV ≥300 mL; low <300 mL; and splenectomy) to compare post-hepatectomy survival rates. RESULTS: Multivariate analyses showed that SV is an independent prognostic factor for overall and disease-free survival. The overall survival rates at 5 years in the high SV, low SV, and splenectomy groups were 39, 75, and 88%, respectively. The overall survival rate in the high SV group was significantly worse than in the low SV and splenectomy groups (P < 0.001). There was no significant difference between the low SV and splenectomy groups (P = 0.831). CONCLUSIONS: High SV is an independent predictor of post-hepatectomy HCC recurrence and overall survival. There is no significant difference in prognosis between low SV and splenectomy groups, even though the latter had high SV. Combined splenectomy with hepatectomy for HCC and PH may improve prognosis and be an appropriate alternative when liver transplantation cannot be performed.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Baço/anatomia & histologia , Baço/cirurgia , Esplenectomia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Humanos , Hipertensão Portal , Imageamento Tridimensional , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Tamanho do Órgão , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
17.
Hepatol Res ; 46(4): 292-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26031324

RESUMO

AIM: We aimed to evaluate whether skeletal muscle mass measured by computed tomography (CT) or bioelectrical impedance analysis (BIA) correlated to muscle strength and physical performance in liver-related hospital cases. METHODS: We prospectively conducted this study in 120 liver-related hospital cases. Skeletal muscle mass was measured by CT scan and BIA. Muscle strength was determined by hand grip strength and physical performance by usual gait speed. RESULTS: Skeletal muscle mass measured using CT significantly correlated to usual gait speed (r(2) = 0.17, P < 0.0001) and hand grip strength (r(2) = 0.66, P < 0.0001), but the correlations were lower using BIA (r(2) = 0.1, P = 0.0005; r(2) = 0.54, P < 0.0001). With regard to liver function, the relationship between skeletal muscle mass measured by CT and BIA and two muscle function parameters in the Child-Pugh A group were significant. In contrast, skeletal muscle mass measured by BIA in the Child-Pugh B or C group was not significantly related to usual gait speed. CONCLUSION: Skeletal muscle mass measured by CT was significantly correlated to hand grip strength and usual gait speed, with higher correlations compared with BIA. Moreover, skeletal muscle mass measured by CT significantly correlated with two muscle functions, even in patients with Child-Pugh B or C.

18.
Liver Transpl ; 26(5): 727-728, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31997556
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