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1.
J Surg Oncol ; 129(4): 765-774, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38105473

RESUMO

BACKGROUND: The usefulness of inflammation-based prognostic scores for early recurrence (ER) after hepatectomy for hepatocellular carcinoma has rarely been reported. This study aimed to evaluate the potential of inflammation-based prognostic scores as predictors of ER and their relationship with tumor markers. METHODS: We enrolled 338 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2021. Clinicopathological factors were compared between patients who developed ER (ER group) and those who did not develop ER (non-ER group). The association between inflammation-based prognostic scores and ER status was evaluated. These scores were compared with those of well-established tumor markers. RESULTS: The platelet-to-lymphocyte ratio (PLR) correlated with ER of hepatocellular carcinoma, with an area under the curve (AUC) value of 0.70, sensitivity of 68.1%, and specificity of 67.7%. In patients with low tumor marker levels, the PLR showed a strong correlation with ER of hepatocellular carcinoma, with an AUC value of 0.851, sensitivity of 100%, and specificity of 76.2%. Multivariate analysis revealed that the PLR was an independent prognostic factor for ER. CONCLUSIONS: The PLR is useful and complementary to tumor markers for predicting ER after hepatectomy for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Prognóstico , Biomarcadores Tumorais , Linfócitos/patologia , Inflamação , Estudos Retrospectivos
2.
Cancer Sci ; 114(11): 4388-4400, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37700464

RESUMO

Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa-2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine-resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti-apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1-heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis-related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Gencitabina , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Mitocôndrias/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pancreáticas
3.
BMC Gastroenterol ; 23(1): 200, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291491

RESUMO

BACKGROUND: The incidence of non-hepatitis B virus, non-hepatitis C virus hepatocellular carcinoma (non-B non-C-HCC) is increasing worldwide. We assessed the clinical characteristics and surgical outcomes of non-B non-C-HCC, versus hepatitis B (HBV-HCC) and hepatitis C (HCV-HCC). METHODS: Etiologies, fibrosis stages, and survival outcomes were analyzed of 789 consecutive patients who underwent surgery from 1990 to 2020 (HBV-HCC, n = 149; HCV-HCC, n = 424; non-B non-C-HCC, n = 216). RESULTS: The incidence of hypertension and diabetes mellitus was significantly higher in patients with NON-B NON-C-HCC than in those with HBV-HCC and HCV-HCC. Significantly more advanced tumor stages were observed in patients with non-B non-C-HCC; however, better liver function and lower fibrosis stages were observed. Patients with non-B non-C-HCC had significantly worse 5-year overall survival than patients with HBV-HCC; overall survival was comparable between patients with non-B non-C-HCC and HCV-HCC. Patients with HCV-HCC had significantly worse 5-year recurrence-free survival than patients with HBV-HCC and non-B non-C-HCC. In patients with non-B non-C-HCC, overall survival was comparable among three periods (1990-2000, 2001-2010, and 2011-2020) despite significant improvement in patients with HBV-HCC and HCV-HCC. CONCLUSION: The prognosis of non-B non-C-HCC was similar to that of HBV-HCC and HCV-HCC regardless of tumor progression at surgery. Patients with hypertension, diabetes mellitus, and dyslipidemia require careful systematic follow-up and treatment.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus , Hepatite C , Hipertensão , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Prognóstico , Hepatite C/complicações , Hepacivirus , Hipertensão/complicações , Hipertensão/epidemiologia , Resultado do Tratamento , Fibrose
4.
World J Surg ; 47(3): 764-772, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36525064

RESUMO

BACKGROUND: Although early enteral nutrition (EEN) is an accepted practice after pancreaticoduodenectomy (PD), the impact of EEN on postoperative complications or nutritional status remains unclear. We aimed to investigate the impact of EEN on delayed gastric emptying (DGE) and nutritional status after PD. METHODS: A total of 143 patients underwent PD between January 2012 and September 2020. We excluded patients who underwent a two-stage pancreatojejunostomy, in whom the enteral tube was accidentally pulled out, or with insufficient information in their medical records. The incidence of postoperative complications was compared between patients who received EEN (EEN group, n = 21) and those who did not (control group, n = 21) after propensity score matching. Univariate and multivariate analyses were performed to identify the risk factors affecting the incidence of these complications. Nutritional status was assessed at postoperative months 1, 3, and 6. RESULTS: The incidence of grade B/C DGE in the EEN group was significantly lower than that in the control group (4.8% vs. 28.6%, p = 0.03). There was no significant difference in overall morbidity, incidence of any other postoperative complications, or all-grade DGE. In multivariate analysis, EEN was associated with a reduction in the incidence of grade B/C DGE (p < 0.01). In the analysis of nutritional status, EEN was significantly associated with better nutritional status at postoperative month 1. CONCLUSION: EEN can lead to a lower clinically relevant DGE rate and better nutritional status in the early postoperative period in patients undergoing PD.


Assuntos
Gastroparesia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Estado Nutricional , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Gastroparesia/prevenção & controle , Nutrição Enteral/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Esvaziamento Gástrico
5.
Ann Surg Oncol ; 29(2): 1437-1448, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34664139

RESUMO

BACKGROUND: Although various biomarkers are useful in predicting cancer prognosis, the most effective preoperative systemic biomarkers for pancreatic ductal adenocarcinoma (PDAC) have not been established. This study aimed to evaluate whether the lymphocyte-to-monocyte ratio (LMR) can predict the long-term outcomes for patients who were to undergo surgical resection of PDAC. METHODS: The study involved 170 patients with PDAC who underwent resection. Multivariate analysis was performed to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS) among clinicopathologic, surgical, and seven systemic biomarker-related factors including LMR. Subgroup analysis of PDAC located in the body and tail of the pancreas (B/T PDAC) was performed (n = 60) to eliminate the influence of preoperative cholangitis and surgical procedure. Furthermore, OS according to the postoperative course of the LMR value group was investigated. RESULTS: A low LMR (<3.3) was the only independent predictive factor for OS (hazard ratio [HR], 3.52; p < 0.001) and DFS (HR, 3.31; p < 0.001) among the systemic biomarkers. Subgroup analysis of the B/T PDAC also showed that low the LMR was the independent predictive factor for OS (HR, 3.24; p = 0.002) and DFS (HR, 4.42; p = 0.003). The PDAC that maintained a high LMR from before surgery to 1 year after surgery showed good long-term outcomes (median OS, 8.5 years; 5-year survival rate, 61.8 %). CONCLUSIONS: Preoperative LMR was an independent predictor of OS and DFS after surgery for PDAC. Maintaining a high LMR through the pre- and postoperative courses might improve the prognosis for patients with PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirurgia , Humanos , Linfócitos , Monócitos , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos
6.
Ann Surg Oncol ; 28(4): 2012-2025, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33044629

RESUMO

BACKGROUND: Although hepatopancreatoduodenectomy (HPD) is the only means of achieving R0 resection of widespread extrahepatic cholangiocarcinoma, its safety and oncological benefit remain controversial because of its inherent high risk of mortality and morbidity. OBJECTIVE: The aim of this study was to retrospectively analyze short- and long-term outcomes and evaluate the safety and oncological benefit of this advanced procedure. METHODS: The study cohort comprised 37 consecutive patients who had undergone major HPD. Portal vein embolization was performed before surgery in 20 (54%) patients with future remnant liver volume < 35%. RESULTS: The median operative time and blood loss were 866 min and 1000 mL, respectively. Concomitant vascular resection was performed in five patients (14%). The overall morbidity and mortality rates were 100% and 5.4% (n = 2), respectively. Nineteen patients (51%) had major (Clavien-Dindo grade III or higher) complications, the most common being intra-abdominal infection (49%) and post-hepatectomy liver failure (46%, grade B/C: 32%/5%), followed by postoperative pancreatic fistula (30%, grade B/C). R0 resection was achieved in 31 patients (84%). The 1-, 3-, and 5-year overall survival (OS) rates were 83%, 48%, and 37%, respectively. In patients with R0 resection, 5-year OS was comparable between patients who had undergone major HPD and major hepatectomy alone (41% vs. 40%, p = non-significant). CONCLUSIONS: HPD is a valid treatment option for extensive cholangiocarcinoma, offering long-term survival benefit at the cost of relatively high but acceptable morbidity and mortality rates. HPD is advocated in selected patients provided that it is considered possible to achieve R0 resection.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento , Universidades
7.
Oncology ; 99(11): 703-712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515195

RESUMO

INTRODUCTION: The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC. METHODS: 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity. RESULTS: The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs. DISCUSSION/CONCLUSION: GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Ducto Colédoco/tratamento farmacológico , Neoplasias do Ducto Colédoco/cirurgia , Desoxicitidina/análogos & derivados , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/cirurgia , Tumor de Klatskin/tratamento farmacológico , Tumor de Klatskin/cirurgia , Ácido Oxônico/efeitos adversos , Tegafur/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ducto Colédoco/mortalidade , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Tumor de Klatskin/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Pontuação de Propensão , Taxa de Sobrevida , Gencitabina
8.
J Surg Oncol ; 124(1): 67-78, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33844858

RESUMO

BACKGROUND AND OBJECTIVES: In today's aging society, surgery is increasingly performed for older patients with perihilar cholangiocarcinoma (PHCC). This study aimed to examine survival and oncological outcomes in octogenarians with PHCC who underwent surgery. METHODS: We retrospectively examined 480 consecutive PHCC patients treated for PHCC between 1991 and 2020. Two hundred forty-seven underwent resection. Patient and clinical characteristics, including postoperative complications, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: The proportion of octogenarians with PHCC undergoing surgery increased from 5.2% in 1991-2000 to 13.4% in 2016-2020. R0 resection and postoperative complication rates were comparable between octogenarians and younger patients. Five-year OS (30.0% vs. 31.7%) and DFS (20.0% vs. 29.5%) did not significantly differ. One-year OS was significantly better in octogenarians who underwent resection than those who did not (95.0% vs. 17.6%; p < .001). Two octogenarians who developed Clavien-Dindo grade III complications had undergone right hemihepatectomy (RH). Posthepatectomy liver failure and biliary leakage (Grade B) were also observed in octogenarians who underwent RH. CONCLUSION: In well-selected octogenarians with PHCC, surgery offers short- and long-term outcomes comparable with those of their younger counterparts. RH may be considered in octogenarians on an individual basis.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/mortalidade , Tumor de Klatskin/cirurgia , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Japão , Tumor de Klatskin/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
9.
World J Surg ; 45(1): 291-301, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32989580

RESUMO

BACKGROUND: The management of positive ductal margins with carcinoma in situ (R1-CIS) after resection is controversial. The aim of this study was to evaluate the impact of R1-CIS on survival in patients who underwent resection for distal cholangiocarcinoma. METHODS: We enrolled 121 consecutive patients with distal cholangiocarcinoma. Poor prognostic factors were investigated by multivariable analysis, and we performed a stratified analysis to evaluate the impact of R1-CIS on survival in patients with or without prognostic factors. RESULTS: Multivariable analysis identified node-positive status as the prognostic factor (P = 0.003). Stratified by lymph node status, overall survival (OS) in the R0 group was significantly better than that in the R1-CIS group in node-negative patients (57.1% vs 30.0%; P < 0.050). Although OS was comparable between the two groups in node-positive patients (5-year OS: 22.2% vs 20.0%, respectively; P = not significant). Furthermore, OS in patients in whom R0 was achieved by additional resection was significantly better than that in patients with R1-CIS (5-year OS: 66.7% vs 30.0%, respectively; P < 0.050). CONCLUSIONS: Remnant CIS is associated with a poor prognosis in patients with node-negative distal cholangiocarcinoma. Every effort should be made to achieve negative bile duct margins.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma in Situ , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
BMC Surg ; 21(1): 107, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653302

RESUMO

BACKGROUND: Peritoneal recurrence of hepatocellular carcinoma (HCC) after hepatectomy occurs rarely, accounting for less than 1% of all recurrences. Reported causes of such dissemination include a history of rupture of the original HCC, needle biopsy or puncture treatment, and surgical procedures. There is no consensus on the optimal treatment strategy for peritoneal dissemination. There have been few reports on assisting resection of peritoneal dissemination by using indocyanine green (ICG) fluorescence. CASE PRESENTATION: A 57-year-old man underwent posterior sectionectomy for HCC. Six months later, computed tomography revealed multiple nodules suspected of indicating peritoneal dissemination. Various preoperative imaging studies demonstrated only four nodules, the doubling time of the tumors being rapid at 22 days. The nodules were therefore resected. ICG (0.5 mg/kg) was injected intravenously 2 days before the procedure, enabling identification of the nodules by their brightness in the operative field under near-infrared lighting. A total of eight lesions were detected during the procedure and resected, some of which had not been identified by preoperative imaging studies. We diagnosed peritoneal dissemination of HCC based on the pathological findings and their similarity to those of the original HCC. We concluded that the recurrences were likely attributable to exposure of the tumor to the serosa at the time of the original operation. CONCLUSIONS: Although ICG fluorescence is useful for identifying peritoneal dissemination of HCC, attention should be paid to the difficulty in detecting deep lesions and occurrence of false positives.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Fluorescência , Humanos , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Peritoneais/cirurgia , Tomografia Computadorizada por Raios X
11.
J Surg Oncol ; 122(6): 1094-1105, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32634266

RESUMO

BACKGROUND: Systemic inflammation may have prognostic value in some malignancies and association with lymph node metastasis. This study aimed to evaluate the impact of systemic inflammatory biomarkers on long-term and oncological outcomes as well as to assess the association between biomarkers with lymph node metastasis in extrahepatic cholangiocarcinoma patients. METHODS: We enrolled 271 consecutive patients who underwent surgical resection for extrahepatic cholangiocarcinoma. Poor prognostic factors were compared to identify the biomarkers that were most associated with overall survival (OS) and disease-free survival (DFS) using receiver operating characteristic curves and multivariable analysis. Furthermore, we evaluated the relationship between biomarkers and lymph node metastasis. RESULTS: Four and two biomarkers were predictive for OS and DFS, respectively, among which, the C-reactive protein-to-albumin ratio (CAR) had the highest area under the curve values (OS: 0.631, DFS: 0.624). Multivariable analysis showed that a high CAR was an independent prognostic factor for both OS and DFS (P = .002 and P < .001, respectively). Although a high CAR was not significantly correlated with lymph node metastasis (P = .645), carbohydrate antigen 19-9 showed a significant correlation (P < .001). CONCLUSIONS: Preoperative CAR is the most accurate prognostic factor for OS and DFS in extrahepatic cholangiocarcinoma patients and is independent of lymph node metastasis.


Assuntos
Albuminas/análise , Neoplasias dos Ductos Biliares/mortalidade , Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Colangiocarcinoma/mortalidade , Hepatectomia/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/sangue , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Cuidados Pré-Operatórios , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida
13.
Mediators Inflamm ; 2015: 362768, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26508816

RESUMO

Proinflammatory cytokines affect several cell functions via receptor-mediated processes. In the kidney, functions of transporters and ion channels along the nephron are also affected by some cytokines. Among these, alteration of activity of potassium ion (K(+)) channels induces changes in transepithelial transport of solutes and water in the kidney, since K(+) channels in tubule cells are indispensable for formation of membrane potential which serves as a driving force for the transepithelial transport. Altered K(+) channel activity may be involved in renal cell dysfunction during inflammation. Although little information was available regarding the effects of proinflammatory cytokines on renal K(+) channels, reports have emerged during the last decade. In human proximal tubule cells, interferon-γ showed a time-dependent biphasic effect on a 40 pS K(+) channel, that is, delayed suppression and acute stimulation, and interleukin-1ß acutely suppressed the channel activity. Transforming growth factor-ß1 activated KCa3.1 K(+) channel in immortalized human proximal tubule cells, which would be involved in the pathogenesis of renal fibrosis. This review discusses the effects of proinflammatory cytokines on renal K(+) channels and the causal relationship between the cytokine-induced changes in K(+) channel activity and renal dysfunction.


Assuntos
Citocinas/metabolismo , Inflamação/metabolismo , Rim/metabolismo , Canais de Potássio/metabolismo , Animais , Transporte Biológico , Fibrose/patologia , Humanos , Rim/patologia , Túbulos Renais/metabolismo , Camundongos , Potássio/química , Fator de Crescimento Transformador beta1/metabolismo
14.
Endocr J ; 61(2): 159-66, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24225429

RESUMO

Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new class of anti-diabetic drug which exerts its glucose-lowering action by suppressing the degradation of a gut incretin hormone glucagon-like peptide-1 (GLP-1). To elucidate whether treatment with stronger DPP-4 inhibitor on top of angiotensin II type 1 receptor blocker (ARB) provides greater renal protective effects, we performed a crossover study with two DPP-4 inhibitors, sitagliptin and alogliptin, in twelve type 2 diabetic patients with incipient nephropathy taking ARBs. This study consisted of three treatment periods: sitagliptin 50 mg/day for 4 weeks (first period), alogliptin 25 mg/day for 4 weeks (second period), and sitagliptin 50 mg/day for 4 weeks (third period). Significant changes in body mass index, blood pressure, serum lipids, serum creatinine, estimated glomerular filtration rate, and HbA1c were not observed among the three treatment periods. Reduced urinary levels of albumin and an oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased urinary cAMP levels, and elevated plasma levels of stromal cell-derived factor-1α (SDF-1α) which is a physiological substrate of DPP-4 were observed after the switch from sitagliptin to a stronger DPP-4 inhibitor alogliptin. Given a large body of evidence indicating anti-oxidative action of cAMP and up-regulation of cellular cAMP production by SDF-1α, the present results suggest that more powerful DPP-4 inhibition on top of angiotensin II type 1 receptor blockade would offer additional protection against early-stage diabetic nephropathy beyond that attributed to glycemic control, via reduction of renal oxidative stress by SDF-1α-cAMP pathway activation.


Assuntos
Albuminúria/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Nefropatias Diabéticas/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Piperidinas/uso terapêutico , Uracila/análogos & derivados , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Quimiocina CXCL12/sangue , Estudos Cross-Over , AMP Cíclico/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas/uso terapêutico , Receptor Tipo 1 de Angiotensina , Fosfato de Sitagliptina , Triazóis/uso terapêutico , Regulação para Cima , Uracila/uso terapêutico
15.
Liver Cancer ; 13(2): 150-160, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38751553

RESUMO

Introduction: Cirrhosis is deemed to be a contributing factor to the postoperative recurrence of hepatocellular carcinoma (HCC); however, the precise impact of liver fibrosis on both cancer-specific prognoses remains unclear. This investigation sought to elucidate the effect of liver fibrosis severity on the cancer-specific prognosis. Methods: A total of 524 consecutive patients were included. Recurrence-free survival (RFS) and disease-specific survival (DSS) were compared according to fibrosis stage. Moreover, postoperative outcomes were subjected to analysis in cohorts of patients with F0 and F1-3, as well as in those with F1-3 and F4, who were carefully matched for background factors. Results: The 5-year RFS exhibited a significantly worse outcome in the F4 group compared to other stages of fibrosis: 5-year RFS - F0 (46.6%), F1-3 (33.1%), and F4 (23.5%), p = 0.03 (F0 vs. F1-3) and p < 0.01 (F1-3 vs. F4). Additionally, the 5-year DSS also presented a significantly worse prognosis in the F4 group: 5-year DSS - F0 (82.9%), F1-3 (73.6%), and F4 (57.4%), p = 0.04 (F0 vs. F1-3) and p < 0.01 (F1-3 vs. F4). In multivariate analysis, fibrosis 1, 2, 3, and 4 stage (compared with F0) (HR: 1.70, 1.81, 1.89, and 3.99, 95% confidence interval: 1.10-1.99, 1.39-2.22, 1.41-2.55, and 2.25-5.01, p = 0.022, p = 0.008, p < 0.001, and p < 0.001, respectively) was independent risk factor for RFS. After matched analysis, both RFS and DSS exhibited significantly worse prognoses in the presence of more advanced fibrosis. There was a significantly higher incidence of multiple recurrences in the F4 group than the F1-3 group, and a number of recurrences were observed both in the same hepatic segment as the resected side and in the contralateral lobe in F4 group. Discussion/Conclusion: The hazard and recurrence pattern of HCC signifies that the prognosis could potentially be poor, as the hepatic fibrosis likely owing to a higher hepatocarcinogenic potential, even in the absence of progression to cirrhotic condition. The risk of de novo recurrence may also increase with the progression of this fibrosis.

16.
Clin Nutr ESPEN ; 59: 176-180, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38220373

RESUMO

OBJECTIVE: A previous study reported an association between sarcopenia and anorexia determined by the simplified nutritional appetite questionnaire (SNAQ) in community-dwelling older adults. However, it is unclear in the community-dwelling older adults who are using outpatient rehabilitation. The purpose of this study was to investigate the relationship between anorexia and sarcopenia as judged by SNAQ in community-dwelling older adults using outpatient rehabilitation. METHODS: This study included 120 older adults (72.5% female). Subjects were provided outpatient rehabilitation one to three times a week. The main outcome was sarcopenia as determined using the Asian working group for sarcopenia 2019. The simplified nutritional appetite questionnaire (SNAQ) was used to assess anorexia. The SNAQ total score range from 4 (worst) to 20 (best), with 13 score and lower considered to indicate anorexia. Statistical analysis was performed by forced-entry logistic regression analysis with sarcopenia as the dependent variable, body mass index (BMI), food intake level scale, anorexia, and propensity score calculated using age, sex, number of medications, updated Charlson comorbidity index as the independent variable. RESULTS: Sarcopenia was observed in 79 of 120 subjects (65.8%). Anorexia was observed in 28 subjects (23.3%). Logistic regression analysis revealed BMI (odds ratio: 0.71 [95% CI: 0.61-0.84]), anorexia (odds ratio: 5.35 [95% CI: 1.24-23.2]) were extracted as a significant variable. CONCLUSIONS: The results of this study show that anorexia as determined by the SNAQ is associated with sarcopenia in community-dwelling older adults using outpatient rehabilitation. This indicates the importance of understanding anorexia in assessing sarcopenia in community-dwelling older adults who are using outpatient rehabilitation.


Assuntos
Anorexia , Sarcopenia , Humanos , Feminino , Idoso , Masculino , Anorexia/complicações , Apetite , Vida Independente , Estudos Transversais , Pacientes Ambulatoriais , Inquéritos e Questionários
17.
Asian J Surg ; 47(2): 893-898, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37923599

RESUMO

OBJECTIVE: Accurate assessment of renal function prior to surgery for hepatocellular carcinoma is important for patient outcome, but current methods such as the estimated glomerular filtration rate (eGFR) are inadequate. We developed a new prediction formula that incorporates preoperative computed tomography (CT) imaging data to determine renal function. METHODS: We retrospectively analyzed 400 patients who underwent hepatectomy for hepatocellular carcinoma between January 2010 and December 2021. Predictors associated with renal function were identified by multivariate analysis. RESULTS: Age, sex, body height, body weight, body surface area, body mass index, serum creatinine, and muscle areas including third lumbar vertebra total muscle area (L3 TMA) determined by preoperative CT were identified as independent predictors likely to be associated with renal function. These were used to construct a new prediction formula using multiple regression analysis performed with a stepwise method: 232.2 + (-1.17 × age) + (-89.0 × serum creatinine) + (0.28 × L3 TMA). The median difference between conventional eGFR and CCr was 47.6 ml/min (range, 1.7-137.9 ml/min), while that between the new eGFR and CCr was 14.3 ml/min (range, 0.02-64.7 ml/min). Spearman rank correlation analysis revealed that the new eGFR was more positively correlated with CCr than conventional eGFR (ρ = 0.623, P < 0.05; ρ = 0.700, P < 0.05, respectively), and hence more accurately reflected renal function. CONCLUSION: A new prediction formula based on L3 TMA determined by CT is more accurate than conventional eGFR for evaluating renal function.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Creatinina , Estudos Retrospectivos , Músculos , Rim
18.
Clin Nutr ESPEN ; 60: 116-121, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38479899

RESUMO

OBJECTIVE: The performance of sarcopenia diagnosis using adductor pollicis muscle thickness (APMT) has been reported. However, the relationship between APMT and low skeletal muscle mass index (SMI) is unclear. The purpose of this study is to investigate the relationship between APMT and low SMI and APMT performance to diagnose low SMI in community-dwelling older women undergoing outpatient rehabilitation. METHODS: This study included 65 older women (mean age: 86.4 years). Subjects were received outpatient rehabilitation one to three times a week. The main outcomes were low SMI as diagnosed using the Asian working group for sarcopenia 2019 and APMT. Logistic regression analysis was performed with low SMI as the dependent variable, APMT, and propensity score calculated using age, sex, number of medications, and updated Charlson comorbidity index as the independent variable. A receiver operating characteristic (ROC) curve of APMT for low SMI was created. A cut-off value was calculated using the Youden index. RESULTS: Among the 65 subjects, 45 (69.2 %) had low SMI. The results of the logistic regression analysis showed a significant association between APMT and low SMI (odds ratio: 0.482 {95 % confidence interval [CI]: 0.313-0.744}). The cut-off value of APMT calculated from the ROC curve was 13 mm. The sensitivity and specificity of this cut-off value were 0.800 (95 % CI: 0.654-0.904) (36 out of 45 subjects) and 0.850 (95 % CI: 0.621-0.968) (17 out of 20 subjects), respectively. The positive predictive value, negative predictive value, and area under the curve were 0.923 (95 % CI: 0.791-0.984), 0.654 (95 % CI: 0.443-0.828), and 0.843 (95 % CI: 0.731-0.955), respectively. The APMT cut-off value of 13 mm is good to identify low SMI. CONCLUSIONS: The results of this study show that APMT is associated with low SMI. Furthermore, the cut-off value of APMT for diagnosing low SMI was 13 mm. The APMT cut-off value of 13 mm is good to identify low SMI. Our findings indicate that measuring APMT is useful for diagnosing low SMI in community-dwelling older women undergoing outpatient rehabilitation.


Assuntos
Dimaprit/análogos & derivados , Estado Nutricional , Sarcopenia , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Sarcopenia/diagnóstico , Avaliação Nutricional , Vida Independente , Pacientes Ambulatoriais , Músculo Esquelético/patologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-38803276

RESUMO

BACKGROUND: The superiority of anatomical liver resection (AR) for localized hepatocellular carcinoma (HCC) over nonanatomical liver resection (NR) remains controversial. This study aimed to investigate the impact of AR in preventing local and early HCC recurrence. METHODS: A total of 280 patients who underwent initial liver resection for solitary HCC ≤5 cm in diameter were categorized into the AR and NR groups and compared using propensity score matching analysis. RESULTS: Between the matched pairs (n = 87 in each group), the incidence rates of local and early (recurrence within 2 years after surgery) recurrences in the AR group were significantly lower than those in the NR group (13.8% vs. 28.7%, p = .025; 20.7% vs. 35.6%, p = .028, respectively). The overall survival in the AR group was better than that in the NR group (median: 13.4 vs. 7.6 years, p = .003). NR was among independent risk factors for early recurrence (odds ratio: 1.98, 95% CI: 1.1-3.6, p = .023) and prognostic factors for local recurrence (hazard ratio: 2.44, 95% CI: 1.4-4.4, p = .003). CONCLUSION: AR is superior in controlling local and early recurrence postoperatively for solitary HCC ≤5 cm in diameter compared with NR.

20.
Am J Surg Pathol ; 48(6): 751-760, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38584480

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.


Assuntos
Neoplasias dos Ductos Biliares , Biomarcadores Tumorais , Proteínas de Ligação ao Cálcio , Colangiocarcinoma , Imuno-Histoquímica , Osteopontina , Humanos , Colangiocarcinoma/patologia , Colangiocarcinoma/classificação , Colangiocarcinoma/mortalidade , Colangiocarcinoma/química , Colangiocarcinoma/diagnóstico , Osteopontina/análise , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/química , Neoplasias dos Ductos Biliares/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Idoso , Estudos Retrospectivos , Proteínas de Ligação ao Cálcio/análise , Adulto , Idoso de 80 Anos ou mais , Proteínas de Neoplasias/análise , Valor Preditivo dos Testes , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/química
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