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1.
Mol Cell Endocrinol ; 539: 111472, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606964

RESUMO

This study investigated the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on skeletal muscles in rats with type 2 diabetes. Male SDT fatty rats (8-week-old) were provided liraglutide, or insulin-hydralazine for 8 weeks; control SDT fatty rats and SD rats were administered a vehicle. At 16 weeks of age, muscle strength of limbs was significantly lower in all SDT fatty rats compared to SD rats. While cross-sectional areas of type IIb muscle fibers in extensor digitorum longus muscle were significantly lower in SDT fatty rats than in SD rats, those of type I muscle fibers in soleus were similar in all rats. In the soleus of SDT fatty rats, liraglutide led to greater citrate synthase activity and cytochrome c oxidase subunit 5 B protein expression, independently of blood glucose and blood pressure levels. Liraglutide may contribute to preservation of mitochondrial content on soleus muscle in type 2 diabetes.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34923497

RESUMO

Background The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia. Methods Eight-week-old SDT fatty rats (n = 12) and Sprague-Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise four times a week from ages 8 to 16 weeks. Results The exercise attenuated hypertension and hyperlipidemia and prevented increases in renal parameter levels without affecting blood glucose levels. In the SDT fatty rats, it prevented induction of renal morphological abnormalities in the interstitium of the superficial and intermediate layers of the cortex. Downregulated expression of endothelial nitric oxide synthase in the glomerulus of the SDT fatty rats was significantly upregulated by the exercise. The exercise upregulated the renal expressions of both medium-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor γ coactivator-1α related to fatty acid metabolism. It increased muscle strength and both muscle weight and cross-sectional area of type IIb muscle fibers in the extensor digitorum longus muscle in the SDT fatty rats. Conclusion Endurance exercise training in type 2 diabetes ameliorates DKD by improving endothelial abnormality and enhancing fatty acid metabolism in addition to attenuated hypertension, hyperlipidemia, and muscle weakness independently of blood glucose levels.

3.
Liver Cancer ; 10(5): 461-472, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34721508

RESUMO

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

4.
Anticancer Res ; 41(11): 5617-5623, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732434

RESUMO

BACKGROUND/AIM: The identification of risk factors for recurrence after resection of colorectal liver metastasis is necessary in order to establish a more effective treatment strategy. In addition to well-known prognostic factors, such as the tumor diameter and number of metastatic tumors, a large amount of intraoperative blood loss (IBL) and blood transfusion have recently been reported to be associated with shorter long-term survival. The aim of this study was to assess the impact of IBL and blood transfusion on the prognosis of colorectal liver metastasis after curative resection. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastasis were enrolled in this study. RESULTS: The high-IBL (>300 ml) group had significantly shorter relapse-free survival after hepatic resection in comparison to the low-IBL (≤300 ml) group (p=0.0025). Patients with blood transfusion had significantly shorter relapse-free survival after hepatic resection in comparison to patients without blood transfusion (p=0.0026). CONCLUSION: A large amount of IBL and blood transfusion may have a negative impact on long-term survival in patients who undergo hepatic resection for colorectal liver metastasis.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Metastasectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/mortalidade , Transfusão de Sangue/mortalidade , Neoplasias Colorretais/mortalidade , Progressão da Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Metastasectomia/efeitos adversos , Metastasectomia/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
5.
World J Surg ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34668046

RESUMO

BACKGROUND: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. METHODS: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. RESULTS: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. CONCLUSIONS: Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

6.
Hepatol Res ; 51(11): 1102-1114, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34476874

RESUMO

AIM: We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. METHODS: Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded. RESULTS: Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC-DAA and DAA-HCC groups. The number of HCC-DAA patients with albumin-bilirubin (ALBI) grade 1 increased from 11 to 15. The disease-free survival rate did not differ between HCC-DAA group (3 years, 60%) and the other two groups (DAA-HCC group, 92% and control group, 60%). The 3-year overall survival rates were better in the DAA-HCC group (84%) and HCC-DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA-induced SVR was neither. CONCLUSIONS: Although postoperative DAA-induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival.

7.
Ann Med Surg (Lond) ; 68: 102644, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34386231

RESUMO

Background: This study aimed to evaluate the prognostic impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma (HCC) in patients with alcohol-related liver disease (ALD). Patients and methods: In total, 92 patients with ALD-HCC who underwent initial and curative hepatic resection were identified, including 56 and 36 patients with and without alcohol abstinence, respectively. Results: The 3-, 5-, and 7-year recurrence-free survival (RFS) were 46%, 43%, and 37% in the abstinence group, and 61%, 36%, and 36% in the non-abstinence group, respectively (p = 0.71). The 3-, 5-, and 7-year overall survival (OS) were 91%, 76%, and 66% in the abstinence group, and 87%, 57%, and 44% in the non-abstinence group, respectively (p = 0.023). Multivariate analysis revealed that non-abstinence was an independent prognostic factor for OS (P = 0.026). The incidence rate of liver-related death including HCC-specific death, liver failure, and renal failure in cirrhosis (hepatorenal syndrome) between the non-abstinence and abstinence groups were 41.7% vs. 19.6% (p = 0.032). Worsening of the Child-Pugh grade at intrahepatic recurrence was more frequently observed in the non-abstinence (33.3%) than that in the abstinence group (6.5%) (p = 0.039). Conclusions: Alcohol abstinence might improve the long-term survival of patients with ALD-HCC undergoing hepatic resection.

8.
World J Surg ; 45(11): 3386-3394, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34244815

RESUMO

BACKGROUND: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status. METHODS: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively). RESULTS: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29). CONCLUSIONS: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos
9.
Front Med (Lausanne) ; 8: 634932, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322499

RESUMO

Background: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also related with future GFR decline in patients with diabetes. The aims of this study are to investigate the association between baseline TNFR levels and early change in TNFR levels by the non-purine selective xanthine oxidase inhibitor, febuxostat, and future eGFR decline chiefly in chronic kidney disease (CKD) patients without diabetes. Methods: We conducted a post-hoc analysis of the FEATHER study on patients with asymptomatic hyperuricemia and CKD stage 3, who were randomly assigned febuxostat 40 mg/day or matched placebo. This analysis included 426 patients in whom baseline stored samples were available. Serum TNFR levels at baseline were measured using enzyme-linked immunosorbent assay. Those levels were also measured using 12-week stored samples from 197 randomly selected patients. Results: Compared with placebo, short-term febuxostat treatment significantly decreased the median percent change from baseline in serum uric acid (-45.05, 95% CI -48.90 to -41.24 mg/dL), TNFR1 (1.10, 95% CI-2.25 to 4.40), and TNFR2 (1.66, 95% CI -1.72 to 4.93), but not TNFR levels. Over a median follow-up of 105 weeks, 30 patients (7.0%) experienced 30% eGFR decline from baseline. In the Cox multivariate model, high levels of baseline TNFR predicted a 30% eGFR decline, even after adjusting for age, sex, systolic blood pressure, high sensitivity C-reactive protein, uric acid, and presence or absence of febuxostat treatment and diabetes, in addition to baseline albumin to creatinine ratio and eGFR. Conclusion: Early change in circulating TNFR levels failed to predict future eGFR decline; however, regardless of febuxostat treatment, the elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia.

10.
Anticancer Res ; 41(5): 2605-2610, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952490

RESUMO

BACKGROUND/AIM: Recently, elevated levels of postoperative inflammatory markers have been reported to be associated with poorer long-term survival outcomes, regardless of the occurrence of infectious complications, in gastroenterological malignancies. The aim of this study was to evaluate the association between postoperative inflammation and shorter long-term survival after resection of colorectal liver metastases. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastases were enrolled. The CRPmax levels were defined as the highest postoperative serum C-reactive protein levels during hospital stay. RESULTS: The high-CRPmax group had a significantly lower relapse-free survival rate than the low-CRPmax group, regardless of the occurrence of infectious complications. CONCLUSION: In colorectal liver metastasis as well as other malignancies, elevated postoperative levels of serum C-reactive protein are associated with shorter long-term survival, regardless of the occurrence of infectious complications.


Assuntos
Proteína C-Reativa/metabolismo , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/microbiologia , Inflamação/patologia , Inflamação/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/cirurgia
11.
Clin J Gastroenterol ; 14(3): 858-865, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33811313

RESUMO

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico
12.
PLoS One ; 16(2): e0247090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33635883

RESUMO

BACKGROUND: Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital. METHODS: A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors. RESULTS: Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests. CONCLUSIONS: Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.


Assuntos
Testes Genéticos/normas , Neoplasias/diagnóstico , Análise de Sequência de DNA/normas , Idoso , Biomarcadores Tumorais/genética , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética , Análise de Sequência de DNA/métodos , Proteína Supressora de Tumor p53/genética
13.
Sci Rep ; 11(1): 982, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441837

RESUMO

We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a-/-) male mice. To induce severe chronic TID after renal IR, unilateral renal ischemia was performed via clamping of the right renal pedicle in both AT1a-/- and wild-type (AT1a+/+) mice for 45 min. While marked renal atrophy and severe TID at 70 days postischemia was induced in the AT1a+/+ mice, such a development was not provoked in the AT1a-/- mice. Although the AT1a+/+ mice were administered hydralazine to maintain the same systolic blood pressure (SBP) levels as the AT1a-/- mice with lower SBP levels, hydralazine did not reproduce the renoprotective effects observed in the AT1a-/- mice. Acute tubular injury at 3 days postischemia was similar between the AT1a-/- mice and the AT1a+/+ mice. From our investigations using IR kidneys at 3, 14, and 28 days postischemia, the multiple molecular mechanisms may be related to prevention of severe chronic TID postischemia in the AT1a-/- mice. In conclusion, inactivation of the AT1 receptor may be useful in preventing the transition of acute kidney injury to chronic kidney disease.


Assuntos
Angiotensina II/metabolismo , Isquemia/metabolismo , Rim/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Insuficiência Renal Crônica/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Hidralazina/farmacologia , Isquemia/tratamento farmacológico , Rim/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Insuficiência Renal Crônica/tratamento farmacológico , Reperfusão/métodos
14.
Clin Exp Nephrol ; 25(4): 365-375, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33409761

RESUMO

BACKGROUND: The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders. METHODS: Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (n = 19) were randomly assigned to three groups. The liraglutide group (n = 6) was injected subcutaneously with liraglutide. Another treatment group (n = 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (n = 7) and non-diabetic Sprague-Dawley rats (n = 7) were injected only with a vehicle. RESULTS: The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment. CONCLUSIONS: Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/farmacologia , Incretinas/farmacologia , Rim/efeitos dos fármacos , Liraglutida/farmacologia , Albuminúria/fisiopatologia , Albuminúria/prevenção & controle , Animais , Autofagia/efeitos dos fármacos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Masculino , Ratos Endogâmicos , Transdução de Sinais
15.
Surgery ; 169(4): 922-928, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33190917

RESUMO

BACKGROUND: Extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection. METHODS: The participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping. RESULTS: Extrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3-5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively. CONCLUSION: We have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon's selection of treatment strategies for hepatocellular carcinoma patients.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Biomarcadores , Carcinoma Hepatocelular/cirurgia , Diagnóstico por Imagem , Feminino , Seguimentos , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Nomogramas , Curva ROC , Resultado do Tratamento , Carga Tumoral
16.
Oncology ; 99(3): 186-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33032274

RESUMO

INTRODUCTION: Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated. METHODS: This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020. RESULTS: Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; p = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; p < 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; p < 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was >90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed. DISCUSSION/CONCLUSION: It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Hemorragia/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinolinas/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
17.
Asian Pac J Cancer Prev ; 21(12): 3647-3654, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33369464

RESUMO

BACKGROUND: Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. METHODS: The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. RESULTS: In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. CONCLUSIONS: Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors.
.


Assuntos
Atrofia/mortalidade , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Hepatectomia/efeitos adversos , Litíase/cirurgia , Hepatopatias/cirurgia , Lesões Pré-Cancerosas/mortalidade , Idoso , Atrofia/etiologia , Atrofia/patologia , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Litíase/patologia , Hepatopatias/patologia , Masculino , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Prognóstico , Taxa de Sobrevida
18.
J Surg Oncol ; 122(8): 1543-1552, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32856301

RESUMO

OBJECTIVE: To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA). METHODS: Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups. RESULTS: After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period. CONCLUSIONS: SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Hepacivirus/efeitos dos fármacos , Hepatectomia/mortalidade , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/virologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resposta Viral Sustentada
19.
World J Surg ; 44(11): 3901-3914, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32651603

RESUMO

BACKGROUND: This study aimed to evaluate the impact of the age-adjusted Charlson comorbidity index (ACCI) on outcomes after hepatic resection for hepatocellular carcinoma (HCC). METHODS: We assessed 763 patients who underwent hepatic resection for HCC. The ACCI scores were categorized as follows: ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7. RESULTS: A multivariate analysis showed that the odds ratios for postoperative complications in ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 0.71 (p = 0.41) and 4.15 (p < 0.001), respectively. The hazard ratios for overall survival of ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 1.52 (p = 0.023) and 2.45 (p < 0.001), respectively. The distribution of deaths due to HCC-related, liver-related, and other causes was 68.2%, 11.8%, and 20% in ACCI ≤ 5 group, 47.2%, 13.9%, and 38.9% in ACCI = 6 group, and 27.3%, 9.1%, and 63.6% in ACCI ≥ 7 group (p = 0.053; ACCI ≤ 5 vs. = 6, p = 0.19; ACCI = 6 vs. ≥ 7, p < 0.001; ACCI ≤ 5 vs. ≥ 7). In terms of the treatment for HCC recurrence in ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7 groups, adaptation rate of surgical resection was 20.1%, 7.3%, and 11.1% and the rate of palliative therapy was 4.3%, 12.2%, and 22.2%, respectively. CONCLUSIONS: The ACCI predicted the short-term and long-term outcomes after hepatic resection of HCC. These findings will help physicians establish a treatment strategy for HCC patients with comorbidities.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fatores Etários , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Comorbidade , Hepatectomia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos
20.
J Hepatobiliary Pancreat Sci ; 27(10): 682-689, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32578373

RESUMO

BACKGROUND: This study aimed to evaluate the prognostic impact of the 5-5-500 rule in patients after hepatic resection for the intermediate stage of hepatocellular carcinoma (HCC; The Barcelona Clinic Liver Cancer classification [BCLC] B). METHODS: 177 patients had hepatic resection for BCLC-B HCC. The 5-5-500 rule was defined by tumor size ≤5 cm in diameter, tumor number ≤5, and α-fetoprotein ≤500 ng/mL. RESULTS: The 3-, 5-, and 7-year recurrence-free survival rates were 22%, 14%, and 11% in patients within the 5-5-500 rule, and 16%, 10%, and 10% in patients beyond the 5-5-500 rule, respectively (P = .015). The 3-, 5-, and 7-year overall survival rates were 72%, 47%, and 34% in patients within the 5-5-500 rule, and 52%, 31%, and 25% in patients beyond the 5-5-500 rule, respectively (P = .035). Being beyond the 5-5-500 rule and liver cirrhosis were independent prognostic factors for recurrence-free survival. For overall survival, being beyond the 5-5-500 rule, age ≥65 years, Child-Pugh class B, and anti-hepatitis C antibody positive were identified as independent prognostic factors. CONCLUSIONS: The 5-5-500 rule could predict prognosis in BCLC-B patients with hepatic resection. Hepatic resection might provide survival benefit for selected patients with BCLC-B HCC within the 5-5-500 rule.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Recém-Nascido , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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