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3.
Cancer Sci ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35466502

RESUMO

The tyrosine kinase inhibitor lenvatinib is used to treat advanced hepatocellular carcinoma (HCC).Ferroptosis is a type of cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Nuclear factor erythroid-derived 2-like 2 (Nrf2) protects HCC cells against ferroptosis. However, the mechanism of lenvatinib-induced cytotoxicity and the relationships between lenvatinib resistance and Nrf2 are unclear. Thus, we investigated the relationship between lenvatinib and ferroptosis and clarified the involvement of Nrf2 in lenvatinib-induced cytotoxicity.Cell viability, lipid ROS levels, and protein expression were measured using Hep3B and HuH7 cells treated with lenvatinib or erastin. We examined these variables after silencing-fibroblast growth factor receptor-4 (FGFR4) or Nrf2 and overexpressing-Nrf2. We immunohistochemically evaluated FGFR4 expression in recurrent lesions after resection and clarified the relationship between FGFR4 expression and lenvatinib efficacy. Lenvatinib suppressed system Xc- (xCT) and glutathione peroxidase 4 (GPX4) expression. Inhibition of the cystine import activity of xCT and GPX4 resulted in the accumulation of lipid ROS. Silencing-FGFR4 suppressed xCT and GPX4 expression and increased lipid ROS levels. Nrf2-silenced HCC cells displayed sensitivity to lenvatinib and high lipid ROS levels. Conversely, Nrf2-overexpressing HCC cells displayed resistance to lenvatinib and low lipid ROS levels. The efficacy of lenvatinib was significantly lower in recurrent HCC lesions with low-FGFR4 expression than in those with high-FGFR4 expression. Patients with FGFR4-positive HCC displayed significantly longer progression-free survival than those with FGFR4-negative HCC.Lenvatinib induced ferroptosis by inhibiting FGFR4. Nrf2 is involvedin the sensitivity of HCC to lenvatinib.

4.
Anesth Analg ; 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35343925

RESUMO

BACKGROUND: Postreperfusion syndrome (PRS) after portal vein reperfusion during liver transplantation (LT) has been reported to cause rapid hemodynamic changes and is associated with a prolonged postoperative hospital stay, renal failure, and increased mortality. Although there are some reports on risk factors for PRS in brain-dead donor LT, there are a few reports on those in living donor LT. Therefore, we retrospectively reviewed the factors associated with PRS to contribute to the anesthetic management so as to reduce PRS during living donor LT. METHODS: After approval by the ethics committee of our institution, 250 patients aged ≥20 years who underwent living donor LT at our institution between January 2013 and September 2018 were included in the study. A decrease in mean arterial pressure of ≥30% within 5 minutes after portal vein reperfusion was defined as PRS, and estimates and odds ratio (OR) for PRS were calculated using logistic regression. The backward method was used for variable selection in the multivariable analysis. RESULTS: Serum calcium ion concentration before reperfusion (per 0.1 mmol/L increase; OR, 0.74; 95% confidence interval (CI), 0.60-0.95; P < .001), preoperative echocardiographic left ventricular end-diastolic diameter (per 1-mm increase: OR, 0.90; 95% CI, 0.85-0.95; P < .001, men [versus women: OR, 2.45; 95% CI, 1.26-4.75; P = .008]), mean pulmonary artery pressure before reperfusion (restricted cubic spline, P = .003), anhepatic period (restricted cubic spline, P = .02), and graft volume to standard liver volume ratio (restricted cubic spline, P = .03) were significantly associated with PRS. CONCLUSIONS: In living donor LT, male sex and presence of small left ventricular end-diastolic diameter, large graft volume, and long anhepatic period are associated with PRS, and a high calcium ion concentration and low pulmonary artery pressure before reperfusion are negatively associated with PRS.

5.
Ann Gastroenterol Surg ; 6(2): 256-264, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35261951

RESUMO

Aim: To investigate the impact of the triple-layered circular stapler compared with the double-layered circular stapler on anastomotic leakage after rectal cancer surgery. Methods: The bursting pressure was compared between porcine ileocolic anastomoses created using a double- or triple-layered stapler. We also retrospectively analyzed the incidence of severe anastomotic leakage in 194 patients who underwent colorectal anastomosis using a double- or triple-layered circular stapler during rectal cancer resection performed in two cancer centers between January 2015 and April 2021. Results: In the porcine model, the bursting pressure was higher in anastomoses created using the triple-layered stapler than the double-layered stapler (end-to-end anastomosis: 26.4 ± 6.2 mm Hg vs 14.5 ± 4.3 mm Hg, P = .0031; side-to-side anastomosis: 27.7 ± 5.0 mm Hg vs 18.0 ± 2.9 mm Hg, P = .0275). Intersectional leakage occurred in 41% and 83% of anastomoses created using the triple- or double-layered stapler, respectively (P = .0821). In the clinical cohort, the double- and triple-layered stapler was used in 153 and 41 patients, respectively. The incidence of anastomotic leakage was lower for anastomoses created using the triple-layered stapler vs the double-layered stapler (0.0% vs 5.8%, P = .0362). In multivariate analysis, the factors independently associated with a lower incidence of anastomotic leakage were female sex (odds ratio: 0.16, 95% confidence interval: 0.01-0.90, P = .0354) and triple-layered stapler usage (odds ratio: 0.00, 95% confidence interval: 0.00-0.96, P = .0465). Conclusion: Anastomoses created using a triple-layered circular stapler had high bursting pressure, which might contribute to a lower incidence of anastomotic leakage after rectal cancer surgery.

6.
Oncol Lett ; 23(3): 93, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35154424

RESUMO

The clinicopathological features of myeloid-derived suppressor cell (MDSC) and CD8+ T-cell infiltration in hepatocellular carcinoma (HCC) are poorly understood. The present study examined MDSC and CD8+ T-cell infiltration in surgically resected primary HCC specimens and investigated the association of MDSC and CD8+ T-cell infiltration with clinicopathological features and patient outcomes. Using a database of 466 patients who underwent hepatic resection for HCC, immunohistochemical staining of CD33 (an MDSC marker) and CD8 was performed. High infiltration of MDSCs within the tumor was observed in patients with a poorer Barcelona Clinic Liver Cancer stage, larger tumor size, more poorly differentiated HCC, and greater presence of portal venous thrombosis, microscopic vascular thrombosis and macroscopic intrahepatic metastasis. MDSC infiltration and CD8+ T-cell infiltration were independent predictors of recurrence-free survival and overall survival, respectively. Stratification based on the MDSC and CD8+ T-cell status of the tumors was also associated with recurrence-free survival (10 year-recurrence-free survival; MDSChighCD8+ T-cellLow, 3.68%; others, 25.7%) and overall survival (10 year-overall survival; MDSChighCD8+ T-cellLow, 12.0%; others, 56.7%). In conclusion, the present large cohort study revealed that high MDSC infiltration was associated with a poor clinical outcome in patients with HCC. Furthermore, the combination of the MDSC and tumor-infiltrating CD8+ T-cell status enabled further classification of patients based on their outcomes.

7.
Magn Reson Imaging ; 87: 104-112, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34999164

RESUMO

PURPOSE: To investigate the utility of T1ρ and T2 relaxations for assessing the severity of liver fibrosis (F stage) and necro-inflammation (A stage) in patients with chronic liver disease (CLD). MATERIALS AND METHODS: We calculated T1ρ and T2 relaxations of the liver parenchyma in 82 patients who underwent liver surgery. F and A stages of enrolled patients were assessed by referring to surgically resected specimens. The relationships between T1ρ or T2 relaxation and F or A stage were assessed using one-way analysis of variance followed by Tukey's multiple comparison test, Spearman's rank correlation test and a receiver operating characteristic analysis. RESULTS: The T1ρ and T2 values of the liver parenchyma were significantly increased as the F and A stages progressed. The T1ρ and T2 values showed significant differences between F0 and F4, between F1 and F4, and between F2 and F4. In addition, T1ρ values showed a significant difference between F0 and F3 as well. The highest diagnostic ability for fibrosis was obtained when differentiating ≥F3 from ≤F2 using T1ρ: the sensitivity was 82.8%, the specificity 79.2% and the area under the curve (AUC) 0.87. The sensitivity and AUC of T1ρ relaxation (46.9% and 0.67) were significantly higher than those of T2 relaxation (29.7% and 0.60) for differentiating ≥A1 from A0. CONCLUSION: T1ρ and T2 relaxations have potential as a biochemical marker for assessing the severity of liver fibrosis and necro-inflammation. T1ρ relaxation may be slightly superior to T2 relaxation in terms of diagnostic ability for liver fibrosis and necro-inflammation.


Assuntos
Cirrose Hepática , Fígado , Área Sob a Curva , Humanos , Inflamação/patologia , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Curva ROC
8.
Hepatol Res ; 52(4): 381-389, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35089647

RESUMO

BACKGROUND: Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. METHODS: Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross-validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non-ER groups and factors for predicting ER and prognosis after HCC resection were compared. RESULTS: Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des-gamma-carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non-ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha-fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non-ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. CONCLUSION: Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection.

9.
Sci Rep ; 12(1): 1517, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087153

RESUMO

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.


Assuntos
Carcinoma Hepatocelular
10.
Br J Cancer ; 126(2): 219-227, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34616011

RESUMO

BACKGROUND: Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients. METHODS: Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated. RESULTS: CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors. CONCLUSION: Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC.


Assuntos
Antígeno B7-H1/metabolismo , Fibroblastos Associados a Câncer/patologia , Caveolina 1/metabolismo , Senescência Celular , Colangiocarcinoma/patologia , Fatores de Transcrição Forkhead/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Idoso , Antígeno B7-H1/imunologia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Linfócitos T CD8-Positivos/imunologia , Fibroblastos Associados a Câncer/metabolismo , Colangiocarcinoma/imunologia , Colangiocarcinoma/metabolismo , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
11.
J Hepatobiliary Pancreat Sci ; 29(1): 33-40, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34866343

RESUMO

BACKGROUND: Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. METHOD: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). RESULTS: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound. CONCLUSION: Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Inquéritos e Questionários
12.
Oncology ; 100(2): 101-113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34724663

RESUMO

INTRODUCTION: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). METHODS: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in 2 independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. RESULTS: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2A histone family member X and checkpoint kinase 1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. CONCLUSIONS: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation.


Assuntos
Biomarcadores Tumorais/genética , Proteína do Grupo de Complementação E da Anemia de Fanconi/genética , Proteína do Grupo de Complementação E da Anemia de Fanconi/metabolismo , Regulação para Cima , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição E2F/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Análise de Sobrevida
13.
Clin J Gastroenterol ; 15(1): 171-176, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34807397

RESUMO

Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography. Technetium galactosyl serum albumin scintigraphy and diagnostic laparoscopy showed that the tumor site was functional, while the surrounding area was a non-functional fibrotic area. A biopsy specimen indicated that the nodular lesion was an FNH-like lesion. She experienced several instances of variceal rupture and suffered liver failure, receiving liver transplantation. The excised liver showed a centrally scarred area in the nodule, indicating that the diagnosis was FNH. We herein report this case as a rare case of FNH that progressed to liver failure.


Assuntos
Hiperplasia Nodular Focal do Fígado , Falência Hepática , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Feminino , Hiperplasia Nodular Focal do Fígado/diagnóstico por imagem , Hiperplasia Nodular Focal do Fígado/cirurgia , Humanos , Hiperplasia/patologia , Fígado/patologia , Neoplasias Hepáticas/patologia
14.
Hepatol Commun ; 6(4): 665-678, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34687175

RESUMO

We examined phosphorylated nuclear factor erythroid 2-related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Antígeno B7-H1 , Carcinoma Hepatocelular/genética , Estudos de Coortes , Humanos , Hipóxia , Neoplasias Hepáticas/genética , Fator 2 Relacionado a NF-E2/genética , Estudos Retrospectivos
15.
J Hepatobiliary Pancreat Sci ; 29(1): 82-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33484112

RESUMO

BACKGROUND: In preparation for the upcoming consensus meeting in Tokyo in 2021, this systematic review aimed to analyze the current available evidence regarding surgical anatomy of the liver, focusing on useful landmarks, strategies and technical tools to perform precise anatomic liver resection (ALR). METHODS: A systematic review was conducted on MEDLINE/PubMed for English articles and on Ichushi database for Japanese articles until September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A total of 3169 manuscripts were obtained, 1993 in English and 1176 in Japanese literature. Subsequently, 63 English and 20 Japanese articles were selected and reviewed. The quality assessment of comparative series and case series was revealed to be usually low; only six articles were qualified as high quality. Forty-two articles focused on analyzing intersegmental/sectional planes and their relationship with specific hepatic landmark veins. In 12 articles, the authors aimed to investigate liver surface anatomic structures, while 36 articles aimed to study technological tools and contrast agents for surgical segmentation during ALR. Although Couinaud's classification has remained the cornerstone in daily diagnostic/surgical practices, it does not always portray the realistic liver segmentation and there has been no standardization on which a single strategy should be followed to perform precise ALR. CONCLUSIONS: A global consensus should be pursued in order to establish clear guidelines and proper recommendations to perform ALR in the era of minimally invasive surgery.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Consenso , Veias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia
16.
Surg Today ; 52(3): 359-368, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754175

RESUMO

In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future.


Assuntos
Transplante de Fígado , Idoso , Humanos , Japão , Fígado , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos
17.
Surg Today ; 52(3): 441-448, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34417867

RESUMO

PURPOSES: Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese-Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. METHODS: The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36-88 years), and their median body weight was 61.5 kg (range 38.4-97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. RESULTS: The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. CONCLUSION: NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Anticancer Res ; 42(1): 245-251, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969731

RESUMO

BACKGROUND/AIM: Mac2-binding protein glycosylation isomer (M2BPGi) is a non-invasive marker for assessing liver fibrosis. This was a retrospective study investigating whether M2BPGi predicts recurrence of hepatocellular carcinoma (HCC) after hepatectomy in patients with HCC who achieved a sustained virological response (SVR). PATIENTS AND METHODS: We retrospectively reviewed the clinicopathological factors from 60 patients who underwent hepatectomy for HCC after achieving a SVR. We divided all patients into high M2BPGi and low M2BPGi groups and analyzed the clinicopathological and surgical outcomes. RESULTS: High M2BPGi (>1.54, n=23) was significantly associated with lower serum albumin, higher ICGR15, higher Fib-4 index, large blood loss, and worse recurrence-free survival compared to low M2BPGi (≤1.54, n=37). Multivariate analysis identified high M2BPGi and large tumor size as being associated with reduced recurrence-free survival. Multivariate analysis identified lower serum albumin, larger tumor size and higher DCP as associated with reduced overall survival. There was no difference regarding recurrence pattern. CONCLUSION: Preoperative M2BPGi is a useful biomarker for HCC recurrence after hepatectomy for SVR-HCC.


Assuntos
Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Glicoproteínas de Membrana/genética , Resposta Viral Sustentada , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Intervalo Livre de Doença , Feminino , Galectina 3/genética , Glicosilação , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
20.
Ann Transplant ; 26: e909493, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34907151

RESUMO

BACKGROUND Portal vein thrombosis (PVT) after pediatric liver transplantation (LT) is a common but grave complication which could eventually result in life-threatening portal hypertension. A "Rex" shunt between the superior mesenteric vein and the Rex recess of the liver has been reported to be a treatment option for extrahepatic portal vein obstruction; however, its application to living donor liver transplantation (LDLT) is limited due to the availability of appropriate vein grafts. In this study, we retrospectively evaluated the effectiveness of Rex shunt as an option for the treatment of PVT after pediatric LDLT. CASE REPORT Three children underwent the Rex shunt for early (n=2) and late (n=1) PVT after LDLT using the greater saphenous vein (n=2) and the external iliac vein (n=1) from the parents who previously donated their livers. Two of the 3 children are free from symptoms with patent shunt grafts at 14 years after the procedures. One child died at 30 days after LDLT due to repeated episodes of PVT, which finally led to hepatic infarction. CONCLUSIONS The Rex shunt is feasible to treat PVT after LDLT. However, additional surgical insults to the living donor need further discussion.


Assuntos
Transplante de Fígado , Trombose Venosa , Criança , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Veia Porta/cirurgia , Estudos Retrospectivos , Trombose Venosa/etiologia , Trombose Venosa/cirurgia
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