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1.
Liver Transpl ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38995149

RESUMEN

Liver transplantation is the definitive treatment for advanced liver cirrhosis with portal hypertension. In Japan, the scarcity of deceased donors leads to reliance on living donors, often resulting in smaller grafts. Managing portal venous pressure (PVP) is critical to prevent fatal posttransplant complications. This study explored the possibility of predicting intraoperative PVP. We analyzed 475 living donor liver transplant cases from 2006 to 2023, excluding those with acute liver failure or prior splenectomy or splenic artery embolization. Patients were divided into a training group (n=425) and a test group (n=50). We evaluated the correlation between preoperative factors and PVP at laparotomy, to predict PVP at laparotomy and closure. The predictive model was validated with the test group data. PVP at laparotomy could be predicted using correlated preoperative factors: prothrombin time ( p <0.001), predicted splenic volume ( p <0.001), and presence of a portosystemic shunt ( p =0.002), as follows: Predicted PVP at laparotomy (mmHg)=25.818 - 0.077×[prothrombin time (%)]+0.004×[predicted splenic volume (ml)] - 2.067×[1: with a portosystemic shunt] ( p <0.001; R=0.346). Additionally, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mmHg)=14.268+0.149×[measured PVP at laparotomy (mmHg)] - 0.040×[GV/SLV (%)] - 0.862×[1: splenectomy (if yes)] - 3.511×[1: splenic artery ligation without splenectomy (if yes)] ( p <0.001; R=0.339).This study demonstrated the feasibility of predicting intraoperative PVP using preoperative factors in liver transplant patients with decompensated cirrhosis. This predictive approach could refine surgical planning, potentially improving patient outcomes.

2.
Surg Today ; 54(7): 812-816, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38170224

RESUMEN

Living-donor liver transplantation (LDLT) is an established treatment for patients with end-stage liver disease or acute liver failure, and outflow reconstruction is considered one of the most vital techniques in LDLT. To date, many strategies have been reported to prevent outflow obstruction, which can be refractory to liver dysfunction and can cause life-threatening graft loss or mortality. In addition, in this era of laparoscopic hepatectomy in donor surgery, especially LDLT using a left liver graft, it has been predicted that cutting the hepatic vein with automatic linear staplers will lead to more outflow-related problems than with conventional open hepatectomy because of the short neck of the anastomosis orifice. We herein review 10 cases of venoplasty performed with a novel venous cuff system using a donor's round ligament around the hepatic vein in LDLT with a left lobe graft, which makes anastomosis of the hepatic vein sterically easy for postoperative venous patency.


Asunto(s)
Estudios de Factibilidad , Venas Hepáticas , Trasplante de Hígado , Donadores Vivos , Venas Mesentéricas , Trasplante de Hígado/métodos , Humanos , Venas Hepáticas/cirugía , Venas Mesentéricas/cirugía , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anastomosis Quirúrgica/métodos , Hepatectomía/métodos , Hígado/irrigación sanguínea , Hígado/cirugía , Ligamentos Redondos/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Laparoscopía/métodos
3.
Cancer Sci ; 114(3): 937-947, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36369960

RESUMEN

The association between tumor microenvironment (TME) and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR-493-5p on tumor cell lines were examined. Additionally, databases were used to identify miR-493-5p targets, and the relationship between prognosis of ICC patients and cocaine- and amphetamine-regulated transcript propeptide (CARTPT), one of the targets of miR-493-5p, expression in ICC tissues was retrospectively analyzed. Compared with NF-derived CM and EVs, CAF-derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR-493-5p was significantly increased in CAF-derived EVs compared to NF-derived EVs. Tumor cell lines transfected with miR-493-5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence-free survival rates were significantly worse in the CARTPT-negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence-free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR-493-5p in EVs.


Asunto(s)
Neoplasias de los Conductos Biliares , Fibroblastos Asociados al Cáncer , Colangiocarcinoma , MicroARNs , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Estudios Retrospectivos , MicroARNs/genética , Proliferación Celular , Línea Celular Tumoral , Colangiocarcinoma/patología , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/metabolismo , Microambiente Tumoral/genética
4.
Ann Surg Oncol ; 30(6): 3378-3389, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36641515

RESUMEN

BACKGROUND: Signal regulatory protein alpha (SIRPα), expressed in the macrophage membrane, inhibits phagocytosis of tumor cells via CD47/SIRPα interaction, which acts as an immune checkpoint factor in cancers. This study aimed to clarify the clinical significance of SIRPα expression in hepatocellular carcinoma (HCC). METHODS: This study analyzed SIRPα expression using RNA sequencing data of 372 HCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of our 189 HCC patient cohort. The correlation between SIRPα expression and clinicopathologic factors, patient survival, and intratumor infiltration of immune cells was investigated. RESULTS: Overall survival (OS) was significantly poorer with high SIRPα expression than with low expression in both TCGA and our cohort. High SIRPα expression correlated with lower recurrence-free survival (RFS) in our cohort. High SIRPα expression was associated with higher rates of microvascular invasion and lower serum albumin levels and correlated with greater intratumor infiltration of CD68-positive macrophages and myeloid-derived suppressor cells (MDSCs). Multivariate analysis showed that SIRPα expression and high infiltration of CD8-positive T cells and MDSCs were predictive factors for both RFS and OS. Patients with high SIRPα expression and infiltration of CD8-positive T cells and MDSCs had significantly lower RFS and OS rates. In spatial transcriptomics sequencing, SIRPα expression was significantly correlated with CD163 expression. CONCLUSIONS: High SIRPα expression in HCC indicates poor prognosis, possibly by inhibiting macrophage phagocytosis of tumor cells, promoting MDSC infiltration and inducing antitumor immunity. Treatment alternatives using SIRPα blockage should be considered in HCC as inhibiting macrophage antitumor immunity and MDSCs.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Relevancia Clínica , Neoplasias Hepáticas/genética , Fagocitosis , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo
5.
Hepatol Res ; 53(8): 723-736, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36998205

RESUMEN

AIM: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors. RESULTS: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group. CONCLUSIONS: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI.

6.
Kyobu Geka ; 76(12): 1055-1060, 2023 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-38057985

RESUMEN

Of 243 resected cases of primary non-small cell lung cancer for ten years in our hospital, we experienced 4 patients (1.6%) of pulmonary pleomorphic carcinoma. All patients were males and heavy smokers. Histologically, the vascular invasion was showed in 3 of 4 patients. In only one patient, recurrence was recognized, and he died 18 months after surgery. The other 3 patients were alive without recurrence for 86, 92, and 60 months after surgery. In general, prognosis of pulmonary pleomorphic carcinoma is very poor. But in my study, 3 of 4 patients of pulmonary pleomorphic carcinoma survive from this disease. As the planning of an appropriate treatment strategy of pulmonary pleomorphic carcinoma,further detailed assessment of adjuvant chemotherapy, such as immune check point inhibitors, will be considered to be necessary.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma , Neoplasias Pulmonares , Masculino , Humanos , Femenino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resultado del Tratamiento , Estadificación de Neoplasias , Carcinoma/cirugía
7.
Semin Liver Dis ; 42(4): 413-422, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36044927

RESUMEN

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.


Asunto(s)
Células Madre Pluripotentes Inducidas , Hepatopatías , Fallo Hepático , Humanos , Porcinos , Animales , Células Endoteliales , Hepatocitos , Hígado/fisiología , Hepatopatías/cirugía
8.
Clin Transplant ; 36(8): e14739, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35642940

RESUMEN

AIM: Recently, new diagnostic criteria for acute-on-chronic liver failure (ACLF) were established in Japan. However, there is little evidence regarding the feasibility of classifying patients undergoing living-donor liver transplantation (LDLT). The aim was to re-evaluate the impact of these new diagnostic criteria on ACLF and the severity classification of patients undergoing LDLT. METHODS: We collected data of 82 recipients who underwent LDLT for liver failure between 1997 and 2020 and reviewed it retrospectively. RESULTS: Of the 82 patients with liver failure, 31 (37.8%) were diagnosed with ACLF; Grade 0 (n = 6), Grade 1 (n = 7), Grade 2 (n = 9), and Grade 3 (n = 9). There was no substantial difference in overall survival (OS) and the occurrence of postoperative complications between liver failure patients with and without ACLF. The OS after LDLT was significantly different among the four groups of ACLF patients (P = .036). Interestingly, ACLF Grade 3 patients had substantially lower OS compared to other ACLF groups even after LDLT (P = .006; 5-year OS rates, 33.3% vs. 85.9%). CONCLUSION: Proper use of the new diagnostic criteria for ACLF in Japan demonstrated that the presence and severity of ACLF, especially the presence of multiple organ failures, leads to morbidity and mortality even in an LDLT setting. Considering that the patients with ACLF Grade 3 do not have the favorable outcomes of LDLT, deceased-donor liver transplantation usage, or LDLT before reaching the severity of Grade 3 may be suitable for further research.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Trasplante de Hígado , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/cirugía , Humanos , Japón/epidemiología , Donadores Vivos , Estudios Retrospectivos , Resultado del Tratamiento
9.
Transpl Int ; 35: 10723, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36568139

RESUMEN

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.


Asunto(s)
Trasplante de Hígado , Masculino , Humanos , Femenino , Donadores Vivos , Estudios Retrospectivos , Músculo Esquelético , Factores de Riesgo , Supervivencia de Injerto , Resultado del Tratamiento
10.
Hepatol Res ; 52(10): 872-881, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35792062

RESUMEN

AIM: Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of adenosine 5'-triphosphate (ATP) for liver regeneration. Mitophagy is a selective process in which damaged, non-functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival. METHODS: We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17-knockdown hepatocyte cell line. RESULTS: Recipients transplanted with low STX17-expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17-expression grafts (88.9% vs. 100%, p < 0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29-88.0, p < 0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59-24.8, p < 0.01) were independent predictive factors for small-for-size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17-knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17-knockdown hepatocyte cell line. CONCLUSION: STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients.

11.
Int J Clin Oncol ; 27(11): 1725-1732, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35962255

RESUMEN

BACKGROUND: There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. METHODS: The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. RESULTS: The median duration of lenvatinib administration was 5.8 months (range, 0.4-24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062-5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016-0.901; P = 0.0393). CONCLUSIONS: Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Compuestos de Fenilurea/uso terapéutico , Resultado del Tratamiento
13.
HPB (Oxford) ; 19(12): 1082-1090, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28888776

RESUMEN

BACKGROUND: Expanding patient selection beyond the Milan criteria in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has long been a matter for debate. We have used the Kyushu University Criteria - maximum tumor diameter <5 cm or des-γ-carboxy prothrombin <300 mAU/ml - in LDLT for HCC since June 2007. The aim of the present study was to present the results of our prospective patient selection by Kyushu University Criteria and to confirm whether or not our criteria were justified. METHODS: The entire study period was divided into the pre-Kyushu era (July 1999-May 2007) and the Kyushu era (June 2007-November 2014). Eighty-nine and 90 patients underwent LDLT for HCC in the pre-Kyushu era and the Kyushu era, respectively. RESULTS: In the pre-Kyushu era, there were significant differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients. In the Kyushu era, however, the differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients disappeared. The 5-year overall patient survival in the Kyushu era was 89.4%. CONCLUSION: Our selection criteria enabled a considerable number of beyond-Milan patients to undergo LDLT without jeopardizing the recurrence-free, and disease-specific, and overall patient survival.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Donadores Vivos , Selección de Paciente , Biomarcadores/sangre , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Precursores de Proteínas/sangre , Protrombina , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
14.
Liver Transpl ; 22(5): 665-76, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26783726

RESUMEN

There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT. Liver Transplantation 22 665-676 2016 AASLD.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Trasplante de Hígado , MicroARNs/genética , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Neoplasias Peritoneales/secundario , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
16.
Ann Surg Oncol ; 23(Suppl 4): 546-551, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27387680

RESUMEN

BACKGROUND: Here, we explored the genetic interactions between diabetes and oncogenic single-nucleotide polymorphisms (SNPs) that determine colorectal cancer (CRC) morbidity. METHODS: 8q24 rs6983267 polymorphism analysis and cDNA microarray were performed in 107 CRCs to identify the genes associated with diabetes and the oncogenic SNP. Then clinical significance of the gene was validated in 132 CRCs. Meta-analysis of microarray data and diabetic comorbidity was performed. RESULTS: Of genes associated with a minor SNP allele at 8q24, diabetes, and MYC overexpression, apolipoprotein A-IV (ApoA-IV) was associated with oncogenesis and poor prognosis in CRC patients. Patients with high ApoA-IV expression showed significantly poorer prognosis by univariate and multivariate analysis. Meta-analysis revealed lipid metabolism was associated with ApoA-IV-related oncogenesis in diabetic patients. CONCLUSIONS: Changes in lipid metabolism associated with aberrant expression of ApoA-IV were risks for CRC oncogenesis.

17.
Ann Surg Oncol ; 23(12): 3948-3955, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27271927

RESUMEN

BACKGROUND: Hypermethylation of DNA silences gene expression and is an important event in colorectal cancer (CRC). This study aimed to identify aberrantly methylated genes that contribute to a poor prognosis for patients with CRC. METHODS: The study comprehensively explored DNA methylation microarray profiles from 396 CRC samples and 45 normal control samples in a database and selected aberrantly methylated transcription factors associated with prognosis and metastasis. Using quantitative reverse transcription polymerase chain reaction, the identified genes in 140 patients with CRC were validated to assess the relationship between expression of methylated genes and prognosis. RESULTS: In the study, FOXE1 was newly identified as a gene associated with prognosis and metastasis in CRC. Expression of FOXE1 in CRC tissues was significantly lower than in normal colorectal tissues (p = 0.01). The survival rate for the patients with low expression of FOXE1 was significantly lower than that for patients with high expression of FOXE1 in uni- and multivariate analyses. Inhibition of DNA methylation recovered FOXE1 expression in CRC cells. CONCLUSIONS: Methylation-mediated silencing of FOXE1 expression was shown to be a potential prognostic factor in CRC.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Metilación de ADN , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Islas de CpG/genética , Epigénesis Genética , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Regiones Promotoras Genéticas , Recto/metabolismo , Tasa de Supervivencia
18.
Clin Exp Hypertens ; 37(5): 411-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25856785

RESUMEN

BACKGROUND: Combination antihypertensive therapy with an angiotensin receptor blocker (ARB) and a calcium channel blocker (CCB) or diuretics is common. This subanalysis investigated blood pressure (BP) variability in patients receiving ARB-based combination therapy. METHODS: In a prospective, randomized, open-label trial, hypertensive outpatients (≥65 years) who did not achieve their target BP with ARB monotherapy switched to losartan 50 mg/hydrochlorothiazide 12.5 mg (ARB + D) or ARB plus amlodipine 5 mg (ARB + C) for 12 months. Clinic BP and heart rate (HR), measured every 3 months, visit-to-visit variability and seasonal variation were evaluated. RESULTS: No significant between-group differences in average, maximum, or minimum systolic or diastolic BP, or HR, were found. Visit-to-visit BP variability (systolic) was significantly higher in the ARB + D group than in the ARB + C group. When each group was subdivided into two seasonal groups (summer and winter), no significant between-group differences in BP were found. Multivariate regression analyses showed a tendency toward negative correlation between outdoor temperature and urinary albumin:creatinine ratio and estimated glomerular filtration rate at 12 months in the ARB + D group. CONCLUSION: Combination therapy with an ARB plus a CCB may be preferable to that with an ARB plus diuretics for decreasing BP variability. As for seasonal variability, both treatments can be used safely regardless of season.


Asunto(s)
Antihipertensivos/administración & dosificación , Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Estaciones del Año , Anciano , Amlodipino/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Losartán/administración & dosificación , Masculino , Estudios Prospectivos , Resultado del Tratamiento
19.
Clin Transplant ; 28(11): 1256-62, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25203425

RESUMEN

Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based modality to evaluate tissue stiffness using short-duration acoustic pulses in the region of interest. Virtual touch tissue quantification (VTTQ), which is an implementation of ARFI, allows quantitative assessment of tissue stiffness. Twenty recipients who underwent living donor liver transplantation (LDLT) for chronic liver diseases were enrolled. Graft types included left lobes with the middle hepatic vein and caudate lobes (n = 11), right lobes (n = 7), and right posterior segments (n = 2). They underwent measurement of graft VTTQ during the early post-LDLT period. The VTTQ value level rose after LDLT, reaching a maximum level on postoperative day 4. There were no significant differences in the VTTQ values between the left and right lobe graft types. Significant correlations were observed between the postoperative maximum value of VTTQ and graft volume-to-recipient standard liver volume ratio, portal venous flow to graft volume ratio, and post-LDLT portal venous pressure. The postoperative maximum serum alanine aminotransferase level and ascites fluid production were also significantly correlated with VTTQ. ARFI may be a useful diagnostic tool for the noninvasive and quantitative evaluation of the severity of graft dysfunction after LDLT.


Asunto(s)
Aloinjertos , Funcionamiento Retardado del Injerto/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad , Supervivencia de Injerto , Fallo Hepático/cirugía , Trasplante de Hígado , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
20.
Surg Today ; 44(11): 2077-85, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24473667

RESUMEN

PURPOSE: To evaluate the anatomical variations in the middle hepatic vein tributaries (V5/V8) for determining the reconstruction strategy in right lobe living donor liver transplantation (LDLT). METHODS: The V5/V8 variations were examined in 268 patients and were classified into three and two types, respectively. The reconstruction rate (RR), patency rate (PR) and clinical outcomes were retrospectively evaluated in 46 right lobe LDLT cases. RESULTS: In terms of V5 variations, the RR and PR were significantly higher for type 2 than type 3 (82.6 vs. 44.4 % and 73.7 vs. 25.0 %, respectively). The alanine aminotransferase level on postoperative day (POD) 5 in the V5 patent group was significantly lower than in the occluded group (123 vs. 191 IU/dL). Regarding V8 variations, the RR and PR were significantly higher for type 1 than type 2 (44.4 vs. 17.6 % and 75.0 vs. 33.3 %, respectively). The aspartate aminotransferase level on POD 3 was significantly lower in the V8 patent group than in the occluded group (50 vs. 121 IU/dL). CONCLUSION: For right lobe grafts with single large V5 (type 2) or V8 (type 1) variations, reconstruction is necessary. Our new classification of the MHV tributaries is useful for determining the reconstruction strategy to use in right lobe LDLT.


Asunto(s)
Venas Hepáticas/anatomía & histología , Venas Hepáticas/diagnóstico por imagen , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Femenino , Humanos , Trasplante de Hígado , Donadores Vivos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica , Estudios Retrospectivos , Adulto Joven
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