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1.
Langenbecks Arch Surg ; 407(8): 3437-3446, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36173461

RESUMO

BACKGROUND: Adjuvant chemotherapy is recommended for patients with pancreatic cancer after curative resection. However, there is limited evidence regarding the efficacy and prognostic factors for adjuvant chemotherapy in patients with stage I pancreatic cancer. This study aimed to identify patients in whom chemotherapy was effective and to detect prognostic factors for stage I pancreatic cancer based on guidelines of the 8th edition of the Union for International Cancer Control (UICC). METHODS: Between 2009 and 2017, 108 patients diagnosed with stage I pancreatic cancer were enrolled in this study. They were distributed into invasion (n = 68) and non-invasion (n = 40) groups. The relationship between clinicopathological variables, including various prognostic factors, disease-free survival (DFS), and overall survival (OS), were investigated by univariate and multivariate analyses. RESULTS: Five-year survival in all patients with stage I pancreatic cancer was 38.9%. Adjuvant chemotherapy failed to improve DFS or OS in patients with stage I cancer (DFS, p = 0.26; OS, p = 0.30). In subgroup analysis, adjuvant chemotherapy significantly improved DFS (multivariate-adjusted hazard ratio (HR), 0.40; 95% confidence interval [CI], 0.21-0.78; p = 0.007) and OS (multivariate-adjusted HR, 0.32; 95% CI, 0.15-0.68; p = 0.003) in the invasion group than in non-invasion group. In contrast, in the non-invasion group, adjuvant chemotherapy failed to improve DFS and OS in univariate analysis (DFS, p = 0.992; OS, p = 0.808). CONCLUSION: For stage I pancreatic cancer, based on guidelines of the UICC 8th edition, adjuvant chemotherapy may benefit patients with extrapancreatic invasion.


Assuntos
Neoplasias Pancreáticas , Humanos , Quimioterapia Adjuvante , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Intervalo Livre de Doença , Modelos de Riscos Proporcionais , Prognóstico , Estadiamento de Neoplasias , Neoplasias Pancreáticas
2.
Int J Clin Oncol ; 27(4): 717-728, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35015195

RESUMO

AIM: Liver fibrosis influences liver regeneration and surgical outcomes. The fibrosis-4 (FIB-4) index is strongly associated with liver fibrosis and cirrhosis. This study aimed to examine the prognostic significance of the combination of FIB-4 index and Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) (PIVKA-II-FIB-4 index score) in patients who underwent curative resection for hepatocellular carcinoma (HCC). METHODS: We included 284 patients who underwent elective hepatic resection for HCC between January 2000 and December 2018. We retrospectively investigated how FIB-4 index is related to disease-free survival and overall survival. RESULTS: According to a receiver operating characteristic (ROC) analysis, the optimal cutoff value of the FIB-4 index was 3.44. In a multivariate analysis, high PIVKA-II and FIB-4 index values were independent predictors of both disease-free survival (P = 0.013 and P = 0.005, respectively) and overall survival (P = 0.048 and P < 0.001, respectively). We classified the PIVKA-II and FIB-4 index levels into two groups (high vs. low) and calculated a new score (PIVKA-II-FIB-4 index score; 0-2) by the sum of each measurement (high, 1; low, 0). The 5 year overall survival rates of patients with PIVKA-II-FIB-4 index scores of 0, 1, and 2 were 84.9, 74.4, and 47.1%, respectively (P < 0.001). CONCLUSION: The combination of the preoperative PIVKA-II and FIB-4 index may be a prognostic factor of HCC after hepatic resection, suggesting that the combined score is useful in assessing the liver fibrosis status in cancer cases.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/cirurgia , Fibrose , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Protrombina , Curva ROC , Estudos Retrospectivos , alfa-Fetoproteínas
3.
Pancreatology ; 21(1): 299-305, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33214083

RESUMO

INTRODUCTION: A soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD. METHOD: This study included 75 patients who underwent PD between November 2014 and April 2020 at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF. RESULTS: Twenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (p < 0.01), soft pancreatic remnant (p < 0.01), high intraoperative blood loss (p < 0.01), high intraoperative amylase level of pancreatic juice (p < 0.01), and low pancreatic fibrosis (p < 0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (p < 0.01) and high intraoperative amylase level of pancreatic juice (p = 0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17 × 105 IU/L (area under the curve = 0.726, sensitivity = 95.7%, and specificity = 50.0%) CONCLUSIONS: The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.


Assuntos
Amilases/análise , Fístula Pancreática/etiologia , Suco Pancreático/enzimologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/enzimologia , Idoso , Perda Sanguínea Cirúrgica , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
4.
J Surg Res ; 258: 414-421, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33109402

RESUMO

BACKGROUND: The preoperative systemic inflammation has been reported to predict tumor recurrence and survival in various cancers, including colorectal liver metastases (CRLM). However, more sensitive biomarker is required to improve perioperative management of CRLM. Therefore, we developed a novel indicator; C-reactive protein-to-lymphocyte ratio (CLR). The aim of this study is to evaluate the prognostic significance of CLR in patients with CRLM after hepatic resection. MATERIALS AND METHODS: The study comprised 197 patients who had undergone hepatic resection for CRLM between January 2000 and December 2018. We retrospectively investigated the relation between CLR and disease-free survival and overall survival after hepatic resection and compared their prognostic significance with that of the C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio. RESULTS: Optimal cutoff level of the CLR by receiver operating characteristics analysis was 62.8 × 10-6. By multivariate analysis, CLR was an independent predictor of disease-free survival [hazard ratio (HR): 1.463, 95% confidence interval (CI): 1.003-2.135, P = 0.048), whereas lymph node metastases>4 (HR: 1.804, 95% CI: 1.100-2.958, P = 0.019) and CLR (HR: 1.656, 95% CI: 1.007-2.724, P = 0.047) were independent predictors of overall survival, while the C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio were not. CONCLUSIONS: CLR may be an independent and significant indicator of poor long-term outcomes in patients with CRLM after hepatic resection.


Assuntos
Proteína C-Reativa/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Idoso , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Japão/epidemiologia , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
5.
Langenbecks Arch Surg ; 406(1): 99-107, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32936328

RESUMO

PURPOSE: The controlling nutritional status (CONUT) score has been reported to predict outcomes in patients with hepatocellular carcinoma (HCC). However, the prognostic significance of the CONUT score in patients with non-B non-C (NBNC) HCC remains to be established. METHODS: The study comprised 246 patients who had undergone elective hepatic resection for HCC between April 2003 and October 2017. We retrospectively investigated the relation between preoperative CONUT score as well as clinicopathological characteristics and disease-free survival (DFS) as well as overall survival (OS). RESULTS: In univariate analyses, CONUT score was associated with DFS and OS in patients with NBNC-HCC (p ≤ 0.01), while there was no significant association of CONUT score with DFS and OS in patients with HBV- and HCV-related HCC (p ≥ 0.1). Of the 111 patients with NBNC-HCC, 97 (87.4%) had CONUT score ≤ 3 (low CONUT score) and the other 14 (12.6%) had CONUT score ≥ 4 (high CONUT score). In the patients with NBNC-HCC, multivariate analysis identified age ≥ 65 years (p = 0.03), multiple tumors (p < 0.01), and high CONUT score (p = 0.03) as the independent and significant predictors of DFS, while multiple tumors (p = 0.01), microvascular invasion (p < 0.01), and high CONUT score (p = 0.01) were the independent and significant predictors of OS. CONCLUSIONS: The CONUT score seems to be a reliable and independent predictor of both DFS and OS after hepatic resection for NBNC-HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Estado Nutricional , Prognóstico , Estudos Retrospectivos
6.
Langenbecks Arch Surg ; 406(3): 883-892, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33404882

RESUMO

PURPOSE: The aim of this study was to evaluate the clinical utility of a novel diagnostic algorithm based on serum D-dimer levels for venous thromboembolism (VTE) after hepatectomy. METHODS: We retrospectively analyzed 742 consecutive patients who underwent hepatectomy in our hospital from 2009 to 2019. From 2015, we routinely measured serum D-dimer level postoperatively and computed tomography was performed when D-dimer level was ≥ 20 µg/mL. RESULTS: VTE was diagnosed in 26 patients and pulmonary embolism (PE) was diagnosed in 18 patients. Multivariate analysis revealed that resected liver weight ≥ 120 g is a significant predictor of VTE (P = 0.011). The incidence of VTE from 2015 to 2019 was greater than that from 2009 to 2014 (5.0% versus 2.1%, P = 0.044). The number of low-risk PE patients between 2015 and 2019 was significantly greater than that between 2009 and 2014 (P = 0.013). There was no in-hospital mortality of patients with PE from 2015 to 2019. CONCLUSION: Patients who undergo hepatectomy are at high risk for VTE, especially when the resected liver weight is high. The proposed diagnostic algorithm based on serum D-dimer levels for VTE after hepatectomy can be useful for early diagnosis.


Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Diagnóstico Precoce , Produtos de Degradação da Fibrina e do Fibrinogênio , Hepatectomia/efeitos adversos , Humanos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Tromboembolia Venosa/diagnóstico por imagem , Tromboembolia Venosa/epidemiologia
7.
Int J Clin Oncol ; 26(10): 1922-1928, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34110531

RESUMO

BACKGROUND: Several kinds of systemic inflammatory response, classified into two types: C-reactive protein (CRP)-based type and blood cell count-based type, were reported as a prognostic indicator in patients with pancreatic cancer (PC). However, there is no consensus which types is more sensitive predictor in patients with PC. Therefore, we here developed a novel biomarker, C-NLR, which consists of both CRP and neutrophil-to-lymphocyte ratio (NLR), and we evaluated the prognostic significance of C-NLR in patients with PC after pancreatic resection. METHODS: A total of 217 patients was comprised in this study. We retrospectively investigated the relation between C-NLR and disease-free survival (DFS) and overall survival (OS) after pancreatic resection. RESULTS: Optimal cutoff level of C-NLR was defined as 0.206 by a ROC analysis. By multivariate analysis, age (P = 0.024), TNM stage (P < 0.001), and C-NLR (HR: 1.373, 95% CI: 1.005-1.874, P = 0.046) were independent predictors of DFS, whereas TNM stage (P = 0.016) and C-NLR (HR: 1.468, 95% CI: 1.042-2.067, P = 0.028) were independent predictors of OS. CONCLUSION: Preoperative C-NLR can be a prognostic indicator in patients with PC after pancreatic resection, suggesting the importance of both CRP and blood cell count in predicting therapeutic outcomes.


Assuntos
Proteína C-Reativa , Neoplasias Pancreáticas , Humanos , Linfócitos , Neutrófilos , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos
8.
Int J Colorectal Dis ; 35(8): 1549-1555, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32382837

RESUMO

PURPOSE: Systemic inflammatory response has been reported to be associated with prognosis in cancer patients. The aim of this study is to investigate the association between Systemic Immune-Inflammation Index (SII), a novel inflammation-based prognostic score and long-term outcomes among patients with colorectal cancer (CRC) after resection. METHODS: We retrospectively investigated 733 patients who underwent resection for CRC between January 2010 and December 2014 at the Jikei University Hospital and explored the relationship between SII, calculated by multiplying the peripheral platelet count by neutrophil count and divided by lymphocyte count, and overall survival. In survival analyses, we conducted Cox proportional hazards models, adjusting potential confounders including TNM stage, serum CEA, serum CA 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and platelet count. RESULTS: In multivariate analysis, age ≥ 65 years (p = 0.003), tumor location (p = 0.043), advanced TNM stage (p < 0.001), serum CA 19-9 > 37 mU/ml (p < 0.001), and SII (P for trend = 0.017) were independent and significant predictors of poor patient survival. Compared to patients with low SII, those with high and intermediate SII patients had poorer survival (Hazard ratio 2.48; 95% CI 1.31-4.69, Hazard ratio 1.65; 95% CI 0.83-3.27, respectively). CONCLUSION: The Systemic Immune-Inflammation Index might be an independent and significant indicator of poor long-term outcomes in patients with CRC after resection.


Assuntos
Neoplasias Colorretais , Inflamação , Idoso , Neoplasias Colorretais/cirurgia , Humanos , Linfócitos , Neutrófilos , Prognóstico , Estudos Retrospectivos
10.
Dig Surg ; 37(4): 275-281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31722357

RESUMO

INTRODUCTION: A preoperative scoring system to predict carcinoma in patients with gallbladder polyps (GBPs). METHODS: Preoperative parameters of patients with GBPs who underwent cholecystectomies were used to construct a scoring system to ascertain the risk of malignancy (reference group). The scoring system developed from this approach was applied to the validation group. RESULTS: In the reference group, 11.5% of patients had carcinomas, in whom the median age was 68 years and the polyp size was 16.9 mm. According to the univariate analysis, the significant factors for carcinoma were age ≥65 years, the presence of gallstones, polyp size ≥13 mm, solitary polyp, and sessile polyp. Age ≥65 years and polyp size ≥13 mm were significant factors according to the multivariate analysis. From these results, we developed a preoperative scoring system to predict carcinoma. The patients were divided into 1 of 2 groups: low-risk and high-risk and their malignancy rates were 4.1 and 61.1% respectively (p < 0.001). In the validation group, the malignancy rate was higher for those in the high-risk group (p = 0.016). CONCLUSIONS: The proposed preoperative scoring system based on simple clinical variables appears to be useful for predicting malignancy in patients with GBPs.


Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Pólipos/diagnóstico por imagem , Pólipos/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma/cirurgia , Colecistectomia Laparoscópica , Diagnóstico Diferencial , Endossonografia , Feminino , Neoplasias da Vesícula Biliar/cirurgia , Cálculos Biliares/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos/cirurgia , Valor Preditivo dos Testes , Período Pré-Operatório , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
11.
J Surg Res ; 238: 102-112, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30769246

RESUMO

BACKGROUND: Inflammation-based prognostic scores are associated with tumor recurrence and survival in various cancers. The aim of this study was to identify the significance of inflammation-based prognostic scores and to detect the most useful score in patients with distal extrahepatic bile duct cancer after pancreaticoduodenectomy. METHODS: Between 2000 and 2015, 121 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic scores and disease-free (DFS) as well as overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve was calculated to compare the predictive ability of each scoring system. Multivariate analysis was performed to identify the clinicopathological variables associated. RESULTS: In univariate analysis, Glasgow prognostic score (GPS), mGPS, C-reactive protein/Alb ratio score, prognostic index, and preoperative monocyte count were significant risk factors for both DFS and OS. The area under the receiver operating characteristics curve of GPS is consistently larger in comparison with other four scores in both DFS as well as OS. In multivariate analysis, GPS was an independent risk factor of both tumor recurrence and poor prognosis. CONCLUSIONS: GPS score is an independent tumor recurrence and prognostic factor in patients with distal extrahepatic bile duct cancer and is superior to the other prognostic scores.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Inflamação/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Pancreaticoduodenectomia/efeitos adversos , Índice de Gravidade de Doença , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Proteína C-Reativa/análise , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Inflamação/sangue , Contagem de Leucócitos , Masculino , Monócitos , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
12.
J Surg Res ; 226: 157-165, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29661282

RESUMO

BACKGROUND: Blood transfusion has been reported to be associated with immunomodulation and poor oncologic outcomes in several malignancies. The aim of the study is to investigate the influence of the use of fresh frozen plasma (FFP) on long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. MATERIALS AND METHODS: The study comprised 127 patients who had undergone first hepatic resection for CRLM between April 2000 and December 2013. We retrospectively investigated the influence of the use of FFP on disease-free survival as well as overall survival and assessed the impact of such a practice on postoperative inflammation markers. RESULTS: In multivariate analysis, more than four lymph node metastases of the primary cancer (P = 0.001), bilobar distribution (P = 0.002), and perioperative FFP transfusion (P = 0.005) were independent risk factors for cancer recurrence, while more than four lymph node metastases of the primary cancer (P < 0.001), presence of neoadjuvant chemotherapy (P = 0.002), and perioperative FFP transfusion (P = 0.004) were independent risk factors for poor overall survival. In patients who underwent FFP transfusion, tumor size (P = 0.004), anatomic resection (P < 0.001), duration of operation (P = 0.039), and intraoperative blood loss (P < 0.001) were significantly greater. Moreover, FFP transfusion was associated with a higher white blood cell level on postoperative day 3 (P < 0.001) and day 5 (P = 0.010) and lower serum C-reactive protein level on postoperative day 1 (P < 0.001) and day 3 (P = 0.017). CONCLUSIONS: Perioperative FFP transfusion is independently associated with poor long-term outcomes in patients with CRLM after hepatic resection. FFP may have an influence on postoperative inflammation because of its immunosuppressive effects.


Assuntos
Transfusão de Componentes Sanguíneos/métodos , Perda Sanguínea Cirúrgica , Neoplasias Colorretais/patologia , Inflamação/diagnóstico , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/imunologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Duração da Cirurgia , Período Perioperatório , Plasma/imunologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
13.
Nihon Shokakibyo Gakkai Zasshi ; 114(10): 1860-1865, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28978886

RESUMO

A 61-year-old man visited our hospital for treatment of a retroperitoneal tumor. The patient had undergone distal gastrectomy for gastric cancer in the past. At 5 years after distal gastrectomy, a retroperitoneal tumor with a large diameter of 30mm was detected by computed tomography and the patient underwent chemotherapy for suspected lymph node metastasis from gastric cancer at a local hospital. However, the retroperitoneal tumor gradually increased, and it was diagnosed finally as asymptomatic paraganglioma. The patient underwent tumor resection and made a satisfactory recovery. He was discharged 11 days after the surgery in a good general condition. Here, we report a case of successful resection of asymptomatic paraganglioma in a patient 5 years after distal gastrectomy for gastric cancer.


Assuntos
Diagnóstico Diferencial , Paraganglioma/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Gastrectomia , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Paraganglioma/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Resultado do Tratamento
14.
J Surg Res ; 206(1): 1-8, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27916347

RESUMO

BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: In vitro, we assessed NF-κB activity and apoptosis under treatment with NM alone (80 µg/mL), with GEM/nPTX, or with a combination of NM and GEM/nPTX in human pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and AsPC-1). In vivo, orthotopic pancreatic cancer mice (BALBc nu/nu) were divided into four groups: control (n = 13), NM (n = 13), GEM/nPTX (n = 13), and triple combination (n = 13). NM (30 mg/kg) was delivered intraperitoneally three times a week, and GEM/nPTX was injected intravenously once a week to orthotopic pancreatic cancer model mice. In the triple combination group, mice received NM followed by GEM/nPTX on the first day to avoid GEM/nPTX-induced NF-κB activation. RESULTS: In vitro and in vivo, NM inhibited GEM/nPTX-induced NF-κB activation, and a synergistic effect of apoptosis was observed in the triple combination group. Furthermore, tumor growth was significantly suppressed in the triple combination group compared with the other groups. CONCLUSIONS: NM enhances the antitumor effect of GEM/nPTX chemotherapy for orthotopic pancreatic cancer by inhibition of NF-κB activation.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Guanidinas/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Albuminas/farmacologia , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Benzamidinas , Biomarcadores/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Esquema de Medicação , Guanidinas/farmacologia , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , Paclitaxel/farmacologia , Neoplasias Pancreáticas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
15.
Hepatol Res ; 46(11): 1099-1106, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26833562

RESUMO

AIM: Hepatitis C virus (HCV) recurrence after liver transplantation decreases survival rates. Improved understanding of the multiple factors influencing HCV recurrence could aid decision-making for donor-recipient pairing and maximize transplant outcomes. The aim of this study was to create a model based on pretransplant variables to stratify patients at risk of HCV-related allograft failure. METHODS: This retrospective study enrolled 154 liver transplant recipients with HCV at Cleveland Clinic. RESULTS: Among the study population, 54 recipients (35.1%) experienced HCV recurrence, histologically defined as moderate to severe hepatitis and/or bridging fibrosis to cirrhosis. The multivariate analysis found donor age (≥60 years, P < 0.002), donor body mass index (≥30 kg/m2 , P < 0.05), African American recipient (P < 0.01) and genotype 1 (P < 0.02) as risk factors for HCV-related allograft failure. When these four factors were scored as a combined index (no factor [n = 15], one factor [n = 76], two factors [n = 43] and three or more factors [n = 20]), the HCV recurrence-free survival showed good stratification according to the scores: 93.3% with no factor, 79.3% with one factor, 52.0% with two factors and 24.4% with three or more factors at 3 years after transplant (P < 0.0001). Moreover, this risk index also identified the patient group at high risk of HCV recurrence after acute rejection. CONCLUSION: While the introduction of direct-acting antiviral agents has been changing the paradigm of HCV treatment, the natural history of recipients with HCV as shown in this study would help estimate the risk of HCV-related allograft failure in those who do not tolerate such new treatment.

16.
World J Surg ; 40(9): 2254-60, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26956901

RESUMO

BACKGROUND: The C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, is associated with outcomes in septic patients. The prognostic value of CRP/Alb ratio has not been established in cancer patients. The aim of this study is to evaluate the significance of CRP/Alb ratio in therapeutic outcome after pancreatic resection for pancreatic cancer. METHODS: The study comprised 113 patients who had undergone pancreatic resection for pancreatic cancer between April 2001 and December 2011. We retrospectively investigated the relation between CRP/Alb ratio and disease-free as well as overall survival. RESULTS: The optimal cut-off level of the CRP/Alb ratio was 0.03. For disease-free survival, preoperative biliary drainage (p = 0.011), advanced tumor-node-metastasis (TNM) classification (p = 0.002), and higher CRP/Alb ratio (p = 0.049) by univariate analysis, and advanced TNM classification (p = 0.003) by multivariate analysis, were independent and significant predictors of cancer recurrence. For overall survival, preoperative biliary drainage (p = 0.012), advanced TNM classification (p = 0.001), and higher CRP/Alb ratio (p = 0.023) by univariate analysis, and advanced TNM classification (p = 0.003) and higher CRP/Alb ratio (p = 0.035) by multivariate analysis, were independent and significant predictors of poor patient outcome. CONCLUSIONS: The CRP/Alb ratio may be an independent and significant indicator of poor long-term outcomes in patients with pancreatic cancer after pancreatic resection.


Assuntos
Proteína C-Reativa/análise , Recidiva Local de Neoplasia/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Albumina Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Prognóstico , Estudos Retrospectivos
17.
World J Surg ; 39(3): 753-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25348884

RESUMO

BACKGROUND: Systemic inflammation as evidenced by the Glasgow prognostic score (GPS) predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS in therapeutic outcome after surgical resection of gallbladder cancer. METHODS: The subjects were 51 patients who underwent surgical resection for gallbladder cancer. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥3.5 g/dl) and normal C-reactive protein (CRP) (≤1.0 mg/dl) as GPS 0 (n = 38), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n = 8), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n = 5). We retrospectively investigated the relation between patient characteristics including GPS, and disease-free as well as overall survival. RESULTS: In disease-free survival, advanced tumor stage based on pathology (p = 0.006), positive lymph node metastasis (p = 0.001), and GPS 1 or 2 (p = 0.006) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, positive lymph node metastasis (p = 0.002) and GPS 1 or 2 (p = 0.032) were independent predictors of poor patient outcome in multivariate analyses. CONCLUSION: The GPS in patients with gallbladder cancer is an independent prognostic predictor after surgical resection.


Assuntos
Carcinoma/sangue , Carcinoma/cirurgia , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/patologia , Inflamação/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Carcinoma/secundário , Colecistectomia/efeitos adversos , Intervalo Livre de Doença , Feminino , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia/efeitos adversos , Humanos , Inflamação/complicações , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Reoperação , Estudos Retrospectivos , Albumina Sérica/metabolismo , Taxa de Sobrevida
18.
J Surg Res ; 192(2): 503-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25043528

RESUMO

BACKGROUND: The receptor for advanced glycation end products (RAGE) is recognized to be responsible for cancer progression in several human cancers. In this study, we investigated the clinical impact of RAGE expression in patients with hepatocellular carcinoma (HCC) after hepatectomy. MATERIALS AND METHODS: Sixty-five consecutive patients who underwent initial hepatectomy for HCC were investigated. The relationships between immunohistochemical expression of RAGE and clinicopathologic features, clinical outcome (overall survival [OS], and disease-free survival [DFS]) were evaluated. RESULTS: The cytoplasmic expression of RAGE in HCC cells was observed in 46 patients (70.8%) and correlated with histologic grade (poorly differentiated versus moderately differentiated HCC, P = 0.021). Five-year OS in RAGE-positive and RAGE-negative groups were 72% and 94%, respectively, whereas 5-y DFS were 29% and 55%, respectively. There were significant differences between OS and DFS (P = 0.018 and 0.031, respectively). Multivariate analysis indicated that RAGE was an independent predictor for both OS and DFS (P = 0.048 and 0.032, respectively). CONCLUSIONS: Our data suggest for the first time a positive correlation between RAGE expression and poor therapeutic outcome. Furthermore, RAGE downregulation may provide a novel therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Hepatectomia/mortalidade , Neoplasias Hepáticas , Receptores Imunológicos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Receptor para Produtos Finais de Glicação Avançada
19.
J Surg Res ; 189(2): 335-9, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24721606

RESUMO

BACKGROUND: High oxygen consumption (OC) in recipients of cadaveric whole liver grafts is associated with a poor prognosis. The aim of this study is to investigate the relationship between intraoperative hepatic OC and graft function and survival in a porcine partial liver graft model. MATERIAL AND METHODS: Experiments followed the Guiding Principles in the Care and Use of Laboratory Animals. Fourteen female pigs, 46-69 kg, received liver allografts of 17%-39% liver volume and were followed for 14 d. We measured donor and recipient body weights, percentage graft weight and expressed it as a percentage of standard liver volume, cold ischemia time, hepatic artery flow (HAF), portal vein flow (PVF), graft volume at sacrifice, serum lactate, prothrombin time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, albumin, total protein, alkaline phosphatase, total bilirubin, and recipient survival. OC was calculated as follows: OC (mL/100 g/min) = ([Hemoglobin {Hb} × 1.34 × SaO2 + 0.003 × PaO2] × HAF + [Hb × 1.34 × SpO2 + 0.003 × PpO2] × PVF - [Hb × 1.34 × SvO2 + 0.003 × PvO2] × [HAF + PVF])/graft weight (100 g), and animals were divided into two groups: low OC group (OC < 2.0 mL/100 g/min) and high OC group (OC ≥ 2.0 mL/100 g/min). RESULTS: In survival analysis, four of seven low OC recipients (57% [n = 7]) survived until the end of the study period compared with one of seven high OC recipients (14% [n = 7]). The low OC group had a significantly higher survival rate than that of the high OC group (P = 0.041). Low OC was associated with higher HAF (mL/100 g/min) after reperfusion compared with that of the high OC group, 29.0 ± 13.8 versus 16.0 ± 11.1 mean ± standard deviation; P = 0.073. Serum alkaline phosphatase and total bilirubin in the low OC group were significantly better than those of the high OC group. Serum lactate was comparable in both groups. Graft weight at the time of sacrifice in the low OC group tended to be higher than that in the high OC group, but not significantly (P = 0.097). CONCLUSIONS: High intraoperative OC is associated with lower HAF, decreased graft function, and decreased survival in the porcine partial liver graft model.


Assuntos
Aloenxertos/metabolismo , Sobrevivência de Enxerto , Transplante de Fígado , Fígado/metabolismo , Consumo de Oxigênio , Animais , Feminino , Suínos
20.
Surg Today ; 44(1): 197-200, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24254059

RESUMO

The etiology of Klippel-Trenaunay syndrome (KTS) is not well understood. Although splenic involvement is very rare in KTS, life-threatening events such as spontaneous rupture of a splenic hemangioma may occur. We recently performed elective splenectomy for massive splenomegaly causing uncontrollable abdominal pain in a woman with KTS. The extracted spleen weighed 4260 g, and cavernous hemangiomas in the spleen were found to be the cause of the splenomegaly. The patient's abdominal pain resolved after surgery and her postoperative course was uneventful, except for persistent bleeding from the bladder. This is a rare case of KTS with associated severe splenomegaly caused by hemangiomas.


Assuntos
Hemangioma Cavernoso/etiologia , Hemangioma Cavernoso/cirurgia , Síndrome de Klippel-Trenaunay-Weber/complicações , Síndrome de Klippel-Trenaunay-Weber/cirurgia , Esplenectomia , Neoplasias Esplênicas/etiologia , Neoplasias Esplênicas/cirurgia , Esplenomegalia/etiologia , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Adulto , Feminino , Hemangioma Cavernoso/patologia , Humanos , Neoplasias Esplênicas/patologia , Esplenomegalia/patologia , Esplenomegalia/cirurgia , Resultado do Tratamento
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