Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 78
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Surg Case Rep ; 67: 86-90, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32045859

RESUMO

BACKGROUND: Subphrenic abscess caused by Clostridium perfringens is rare after hepatic resection. We herein report such a case after hepatic resection for hepatocellular carcinoma following treatment of emphysematous cholecystitis. CASE PRESENTATION: A 69-years-old man with chronic hepatitis B, was admitted to our hospital for right subcostal pain and loss of appetite. Computed tomography (CT) revealed emphysematous cholecystitis, for which percutaneous transhepatic gallbladder drainage was performed. Clostridium perfringens was identified from the culture of the bile. Imaging studies immediately demonstrated hepatocellular carcinoma with right lobe of the liver, for which the patients underwent hepatic resection and cholecystectomy concomitantly. After operation, the patient developed emphysematous subphrenic abscess on postoperative day 15, for which CT-guided percutaneous drainage was performed. Clostridium perfringens was identified from the culture of the abscess fluid. The patient was given Ciprofloxacin and Clindamycin and made a satisfactory recovery. The patient was discharged on POD 95 and remains well with no evidence of tumor recurrence as of 8 years after resection. CONCLUSION: We herein reported a subphrenic abscess due to Clostridium perfringens after hepatic resection for hepatocellular carcinoma following emphysematous cholecystitis.

2.
Anticancer Res ; 40(1): 293-298, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892579

RESUMO

BACKGROUND/AIM: The prognosis of pancreatic cancer remains poor with a high incidence of recurrence even after curative resection. The aim of this study was to investigate prognostic factors in patients with recurrent pancreatic cancer using the multicenter database. PATIENTS AND METHODS: The subjects were 196 patients with recurrent pancreatic cancer who underwent resection between 2008 and 2015. We retrospectively investigated the relation between clinicopathological characteristics of the patients and overall survival from recurrence using univariate and multivariate analyses. RESULTS: In univariate analysis, the positive lymphatic invasion (p=0.0240), time to recurrence from resection <1 year (p<0.0001), sites of recurrence except for local or lymph node (p=0.0273), liver recurrence (p=0.0389) and peritoneal recurrence (p<0.0001) were significantly associated with poor overall survival from recurrence. In multivariate analysis, time to recurrence from resection <1 year (p<0.0001) and peritoneal recurrence (p<0.0001) were independently associated with poor overall survival from recurrence. CONCLUSION: Time to recurrence from resection <1 year and peritoneal recurrence were significant independent predictors of poor overall survival from recurrence in patients with recurrent pancreatic cancer.


Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Peritoneais/patologia , Prognóstico
3.
J Pathol ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880318

RESUMO

Fusobacterium nucleatum (F. nucleatum), which has been associated with colorectal carcinogenesis, can impair anti-tumour immunity, and actively invade colon epithelial cells. Considering the critical role of autophagy in host defence against microorganisms, we hypothesised that autophagic activity of tumour cells might influence the amount of F. nucleatum in colorectal cancer tissue. Using 724 rectal and colon cancer cases within the Nurses' Health Study and the Health Professionals Follow-up Study, we evaluated autophagic activity of tumour cells by immunohistochemical analyses of BECN1 (beclin 1), MAP1LC3 (LC3), and SQSTM1 (p62) expression. We measured the amount of F. nucleatum DNA in tumour tissue by quantitative polymerase chain reaction (PCR). We conducted multivariable ordinal logistic regression analyses to examine the association of tumour BECN1, MAP1LC3, and SQSTM1 expression with the amount of F. nucleatum, adjusting for potential confounders, including microsatellite instability status; CpG island methylator phenotype; long-interspersed nucleotide element-1 methylation; and KRAS, BRAF, and PIK3CA mutations. Compared with BECN1-low cases, BECN1-intermediate and BECN1-high cases were associated with lower amounts of F. nucleatum with odds ratios (for a unit increase in three ordinal categories of the amount of F. nucleatum) of 0.54 (95% confidence interval, 0.29-0.99) and 0.31 (95% confidence interval, 0.16-0.60), respectively (Ptrend < 0.001 across ordinal BECN1 categories). Tumour MAP1LC3 and SQSTM1 levels were not significantly associated with the amount of F. nucleatum (Ptrend > 0.06). Tumour BECN1, MAP1LC3, and SQSTM1 levels were not significantly associated with patient survival (Ptrend > 0.10). In conclusion, tumour BECN1 expression is inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting a possible role of autophagy in the elimination of invasive microorganisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

4.
Anticancer Res ; 39(11): 6325-6332, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704863

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or older; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and older may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and older, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Comorbidade , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Margens de Excisão , Complicações Pós-Operatórias , Análise de Sobrevida , Resultado do Tratamento
5.
Anticancer Res ; 39(9): 5143-5148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519626

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or over; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and over may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and over, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Resultado do Tratamento
6.
Int Cancer Conf J ; 8(4): 190-194, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31559121

RESUMO

Breast cancer is known to metastasize to all organs of the body. However, abdominal lymph node metastases from breast cancer are extremely rare. We herein report a resected case of an invasive pancreatic ductal adenocarcinoma (PDAC) in which abdominal lymph node metastases from breast cancer were diagnosed. A 54-year-old woman was pointed out to have a tumor in the pancreatic tail with dilatation of the distal pancreatic duct. She had undergone partial mastectomy for left breast cancer at the age of 51 years and had undergone partial liver resection for liver metastasis in the segment 3/4 6 months earlier. Computed tomography revealed a low-density tumor in the pancreatic tail with dilated distal main pancreatic duct. Magnetic resonance imaging (MRI) exhibited a high-intensity tumor in the pancreatic tail in diffusion-weighted images. With a diagnosis of pancreatic cancer, distal pancreatectomy and splenectomy with lymph nodes dissection was performed. Lymph node metastases along the splenic artery were pathologically similar to PDAC. However, lymph node metastases along the left gastric artery, common hepatic artery, celiac axis, and superior mesenteric artery were pathologically similar to breast cancer. Immunohistochemistry staining of abdominal lymph nodes with GATA-3 was positive, which strongly suggested metastatic breast cancer. Although she received chemotherapy with S-1 for breast cancer and PDAC for 4 months, MRI showed multiple liver metastases derived from breast cancer. Finally, she died 12 months after operation.

7.
Surg Case Rep ; 5(1): 103, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236705

RESUMO

BACKGROUND: Metastatic biliary tract cancer (BTC) has poor prognosis. Recently, patients with metastatic BTC who respond well to systemic chemotherapy can be treated by radical resection or "conversion surgery." CASE PRESENTATION: A 67-year-old male patient was diagnosed with intrahepatic cholangiocarcinoma with para-aortic metastases [cT2N1M1, stage IVB]. He was enrolled in our phase II study for unresectable BTC consisting of cisplatin (25 mg/m2 i.v. for 30 min) followed by gemcitabine (1000 mg/m2 i.v. for 30 min) on days 1 and 8 and oral S-1 on alternate days. After 8 courses of this regimen, marked regression of para-aortic lymph metastases was achieved, and we performed extended left hepatic lobectomy with the caudate lobe, concomitant portal vein resection, and lymph node dissection including the para-aortic region. The patient made a satisfactory recovery and was discharged on postoperative day 25. Histopathological examination revealed more than 50% of the tumor area replaced with fibrosis, and curative resection was achieved (ypT2N1M1, stage IVB, Evans criteria IIb). The patient received adjuvant chemotherapy using S-1 for 12 months and remains well with no evidence of tumor recurrence as of 48 months after surgery. CONCLUSIONS: We herein report a successfully treated case of advanced BTC with para-aortic lymph node metastases by conversion surgery after combination chemotherapy using gemcitabine, cisplatin, and S-1.

8.
J Gastrointest Surg ; 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31062271

RESUMO

AIMS: The benefit of preoperative biliary drainage for patients with operable periampullary cancers is controversial because biliary drainage would activate inflammatory response such as cholangitis. The aim of this study was to identify a novel prognostic score in patients with operable periampullary cancers including pancreatic cancer and extrahepatic distal bile duct cancer with a typical reference to preoperative biliary drainage and inflammatory status. METHODS: Between 2000 and 2015, 246 patients were enrolled in this retrospective study. The patients were divided into four groups of the following three factors; the presence of preoperative biliary drainage, decreased serum albumin value (< 3.5 g dl-1), and increased CR P value (> 1.0 mg dl-1). The relationship between clinicopathological variables and disease-free survival (DFS) as well as over-all survival (OS) was investigated by univariate and multivariate analyses. To compare the sensitivity and specificity among the types of cancer, the area under the receiver operating characteristics curve (AUC) was evaluated in patients with pancreatic cancer and extrahepatic distal bile duct cancer. RESULTS: In multivariate analysis of DFS and OS, the novel prognostic factor combining preoperative biliary drainage and inflammatory status was an independent risk factor of tumor recurrence and prognosis as well as differentiation of the tumor and resected margin. CONCLUSION: The novel prognostic score combining preoperative biliary drainage and inflammatory status may be an independent predictor of tumor recurrence and prognosis in patients with periampullary cancers.

9.
Clin J Gastroenterol ; 12(6): 552-555, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30955165

RESUMO

Everolimus is an mTOR (the mammalian target of rapamycin) inhibitor, which is used for the treatment of advanced renal cell carcinoma. Life-threatening hemorrhages are extremely rare adverse effect of everolimus. We herein report a successfully treated case of severe everolimus-related gastrointestinal hemorrhage by emergency surgical resection for patient with advanced renal cell carcinoma. A 72-year-old male was diagnosed with renal cell carcinoma, for which everolimus was administered after unsuccessful treatment with sunitinib and sorafenib. The patient suddenly developed hematemesis 4 weeks after administration. Upper gastrointestinal endoscopy showed gastric antral vascular ectasia. Once the hemorrhage was successfully cauterized by argon plasma coagulation, everolimus was discontinued. However, the patient after re-administration of everolimus developed hematemesis again and exhibited hemorrhage shock. Since therapeutic endoscopy could not achieve hemostasis, the patient underwent emergency distal gastrectomy with Billroth I reconstruction. The patient's vital signs and hemoglobin level stabilized after the surgery. Thereafter, the patient made a satisfactory recovery, and was discharged on postoperative day 10.

10.
Anticancer Res ; 39(3): 1469-1478, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842184

RESUMO

BACKGROUND/AIM: Prediction of local recurrence and distant metastasis is important for patients with pancreatic cancer following pancreatic resection. The aims of this study were to identify a novel prognostic score which combines distance from common hepatic artery (CHA) or superior mesenteric artery (SMA) and examine serum CA19-9 for predicting local recurrence in patients with pancreatic cancer following resection. PATIENTS AND METHODS: This retrospective study comprised 149 patients who went through elective pancreatic resection for pancreatic cancer between June 2007 and December, 2017. We established new scores (CHA score and SMA score) using the distance between CHA or SMA and the tumor measured by preoperative CT scan in combination with preoperative serum CA19-9 values. We evaluated the relationship between the scores and local recurrence of pancreatic cancer. Finally, we investigated the relationship between the scores and local recurrence-free survival as well as the overall survival. RESULTS: The optimal cut-off levels of the distance between CHA or SMA and the tumor, as determined by ROC analysis, were 20.55 and 10.9 mm, respectively. In a logistic progression model, demonstrated by multivariate analysis, lymphatic invasion (p=0.002), preoperative serum CA19-9 (p=0.007) and SMA score (p=0.004) were identified to be independent predictors of local recurrence in patients with pancreatic cancer following resection. In a Cox progression model, demonstrated by multivariate analysis, intraoperative blood loss (p=0.022), lymphatic invasion (p=0.001) and SMA score (p<0.001) were identified as independent factors of local recurrence. The independent predictors of poor overall survival by multivariate analysis consisted of intraoperative blood loss (p=0.045), intraoperative transfusion (p=0.026) and SMA score (p<0.001). CONCLUSION: The SMA score may be an independent preoperative predictor of local recurrence and prognosis in patients with pancreatic cancer.


Assuntos
Antígeno CA-19-9/sangue , Artéria Mesentérica Superior/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pancreáticas , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X , Ultrassonografia
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.

12.
Anticancer Res ; 38(11): 6491-6499, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396977

RESUMO

AIM: Prognostic factors of recurrence and survival in various cancer types have been reported and include C-reactive protein (CRP)-based measures as evidenced by the Glasgow prognostic score (GPS), as well as peripheral blood cell-based prognostic values such as the prognostic index (PI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The aim of this study was to identify significant prognostic values and compare them for suitability for use in patients after curative pancreatic resection for pancreatic cancer. MATERIALS AND METHODS: Between 2000 and 2015, 188 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic values and disease-free (DFS) and overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve (AUC) was evaluated to compare the predictive ability of each of these scoring systems. Multivariate analysis was then performed to identify clinicopathological variables that associated DFS and OS. RESULTS: In univariate analysis, GPS, modified GPS, CRP to albumin ratio and PI were significant risk factors for both DFS and OS. The AUC of CRP-based scores (GPS, modified GPS, and CRP to albumin ratio) were consistently larger in comparison with PI, which consists of both CRP and peripheral blood cell scores, at all time points for both DFS and OS. In multivariate analysis, GPS was the only independent risk factor of tumor recurrence and survival. CONCLUSION: CRP-based prognostic scores have an independent value for both tumor recurrence and prognosis in patients after curative resection for pancreatic cancer, and are superior to other peripheral blood cell count-based prognostic scores.


Assuntos
Proteína C-Reativa/metabolismo , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
13.
Case Rep Gastroenterol ; 12(2): 504-512, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30283284

RESUMO

Simultaneous resection of synchronous hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) is extremely rare. Case 1 is a 64-year-old woman, who had undergone anterior resection for rectal cancer 3 years earlier was pointed out to have a cystic tumor in the pancreatic tail and a solitary tumor in the liver. CT revealed a hypovascular tumor in the pancreatic tail and a liver tumor with early enhancement. With a diagnosis of simultaneous HCC and PDAC, she underwent laparotomy, in which intraoperative frozen section examination of the liver was compatible with HCC. Therefore, she underwent hepatic resection as well as distal pancreatectomy and splenectomy. The patient received adjuvant chemotherapy with S-1 and remains well with no evidence of tumor recurrence as of 28 months after resection. Case 2 is a 73-year-old man with sustained viral response to antiviral treatment for hepatitis C virus, who was pointed out to have a tumor in the pancreatic head and a solitary tumor in the liver. Gadoxetic acid-enhanced MRI exhibited enhancement compatible with HCC. With a diagnosis of concomitant HCC and PDAC, surgery was performed. Intraoperative frozen section examination was compatible with HCC, for which a pancreaticoduodenectomy was performed. The patient received adjuvant chemotherapy with S-1 and remains well with no evidence of tumor recurrence as of 16 months after resection. In conclusion, we describe 2 cases of hepato-pancreatectomy for synchronous double primary cancers of the pancreas and the liver, where exclusion of the liver tumor as a metastatic lesion from the pancreatic cancer is important.

14.
Mol Clin Oncol ; 9(4): 369-376, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214725

RESUMO

Liver function is a major prognostic factor following hepatic resection for hepatocellular carcinoma (HCC), which is well correlated with the degree of fibrosis. On the other hand, the presence of liver cirrhosis itself leads to a higher incidence of HCC than chronic hepatitis. Therefore, preoperative noninvasive markers of fibrosis are important for the assessment of prognosis for treatment of HCC. The present study aimed to analyze whether aspartate aminotransferase to platelet ratio index (APRI) could predict prognosis following hepatic resection for HCC. The subjects were 162 patients who underwent hepatic resection for HCC between January 2000 and December 2011. The relationship between APRI and disease-free and overall survival were retrospectively investigated. In multivariate analysis, indocyanine green at 15 min (ICG-R15) ≥15% (P=0.0306), APRI ≥0.45 (P=0.0184), perioperative blood transfusion of red cell concentrates (RCC; P=0.0034) and TNM stage II, III or IV (P=0.0184) were significant predictors in disease-free survival. For overall survival, ICG-R15 ≥15% (P=0.0454), APRI ≥0.45 (P=0.0417), perioperative blood transfusion of RCC (P=0.0036) and TNM stage II, III or IV (P=0.0033) were significant predictors. In addition, higher APRI values were positively correlated with hepatitis C virus infection and preoperative liver function. In conclusion, APRI is an independent risk factor for disease-free and overall survival following hepatic resection for HCC.

15.
Ann Gastroenterol Surg ; 2(1): 65-71, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29863120

RESUMO

Pancreatic cancer is often resistant to chemotherapy. We previously showed the efficacy of combination treatment using gemcitabine and nafamostat mesilate (FUT-175) for patients with unresectable pancreatic cancer. However, the mechanisms that affect the sensitivity of FUT-175 are not fully understood. The purpose of the present study was to clarify the mechanism of the sensitivity to FUT-175, with a focus on the activity of glycogen synthase kinase-3ß (GSK-3ß). In vitro, we assessed sensitivity to FUT-175 in human pancreatic cancer cell lines (PANC-1 and MIAPaCa-2) and difference of signaling in these cells by cell proliferation assay, Western blot analysis and microarray. Next, we assessed cell viability, apoptotic signal and nuclear factor-kappa B (NF-κB) activity in response to treatment with FUT-175 alone and in combination with GSK-3 inhibitor or protein phosphatase 2A (PP2A) by cell proliferation assay, Western blot analysis and enzyme-linked immunosorbent assay. Phosphorylated GSK-3ß level was significantly higher in MIAPaCa-2 (high sensitivity cell) than in PANC-1 (low sensitivity cell). Cell viability and NF-κB activity were significantly decreased by addition of GSK-3 inhibitor to FUT-175, and levels of cleaved caspase-8 were increased by inhibition of GSK-3. PP2A inhibitor increased the levels of phosphorylated GSK-3ß and sensitized both cell lines to FUT-175 as measured by cell viability and apoptotic signal. The results indicate that GSK-3ß activity plays a key role in the antitumor effect of FUT-175 in pancreatic cancer cells, and regulation of GSK-3ß by PP2A inhibition could be a novel therapeutic approach for pancreatic cancer.

16.
Surgery ; 164(3): 404-410, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29754978

RESUMO

BACKGROUND: Liver function in patients with hepatocellular carcinoma is generally graded according to the Child-Pugh system; however, some variables in the Child-Pugh grade are subjective. We developed a novel, objective score called the prothrombin time-international normalized ratio to albumin ratio. The aim of this study was to evaluate the prognostic value of this new score in patients with hepatocellular carcinoma after hepatic resection. METHODS: The study comprised 199 patients who underwent elective hepatic resection for hepatocellular carcinoma between January 2003 and December 2014. We investigated retrospectively the relation between prothrombin time-international normalized ratio to albumin ratio, disease-free survival, and overall survival and compared the value of liver functional reserve between prothrombin time-international normalized ratio to albumin ratio and Child-Pugh grade. RESULTS: The optimal cut-off level of the prothrombin time-international normalized ratio to albumin ratio was 0.288. In multivariate analysis, the independent and significant predictors of cancer recurrence consisted of hepatitis C virus infection (P = .043), preoperative retention rate of indocyanine green at 15 minutes ≥15% (P = .039), the presence of multiple tumors (P = .001) or microvascular invasion (P < .001), and prothrombin time-international normalized ratio to albumin ratio ≥0.288 (P = .022). The independent predictors of poor overall survival were microvascular invasion (P = .001) and prothrombin time-international normalized ratio to albumin ratio ≥0.288 (P = .001). In patients with a high prothrombin time-international normalized ratio to albumin ratio, pathologic liver cirrhosis (P < .001), postoperative ascites (P = .039), and postoperative liver failure (P = .040) were greater than for their counterparts. CONCLUSION: The prothrombin time-international normalized ratio to albumin ratio may reflect liver function and may be a novel indicator of poor long-term outcome in patients with hepatocellular carcinoma after hepatic resection.


Assuntos
Carcinoma Hepatocelular/sangue , Coeficiente Internacional Normatizado , Neoplasias Hepáticas/sangue , Tempo de Protrombina , Albumina Sérica , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
17.
Oncotarget ; 9(20): 15292-15301, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29632644

RESUMO

Introduction: Nuclear factor κB (NF-κB) plays an important role in cancer progression and causes therapeutic resistance to chemotherapy. Pomalidomide, a third-generation immunomodulating drug derived from thalidomide, has been approved for uncontrolled multiple myeloma. We hypothesized that pomalidomide may inhibit the anticancer agent-induced NF-κB activity and enhance chemosensitization of combination chemotherapy with gemcitabine and S1 (Gem/S1) in pancreatic cancer. Methods: In vitro, we assessed NF-κB activity, induction of caspase cascade, cell apoptosis and cell proliferation using human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). In vivo, we established an orthotopic xenograft mouse model for human pancreatic cancer by injection of PANC-1 cells. At 5 weeks after injection, the animals were randomly divided into four groups and treated with Gem (100 mg/kg) /S1 (10 mg/kg), with oral administration of pomalidomide (0.5 mg/kg), with combination of gemcitabine, S1, and pomalidomide or vehicle only. Results: Although chemotherapeutic agents induced NF-κB activation in pancreatic cancer cells, pomalidomide inhibited anticancer agent-induced NF-κB activation (p < 0.01). Of the four groups tested for the apoptosis-related caspase signals and apoptosis under both in vitro and in vivo conditions, Gem/S1/Pomalidomide group demonstrated the strongest activation of the caspase signals and proapoptotic effect. In Gem/S1/Pomalidomide group, cell proliferation and tumor growth were slower than those in other groups both in vitro and in vivo (p < 0.01). There were no obvious adverse effects except for thrombocytosis by using pomalidomide. Conclusions: Pomalidomide promotes chemosensitization of pancreatic cancer by inhibiting chemotherapeutic agents-induced NF-κB activation.

18.
Oncotarget ; 9(21): 15780-15791, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29644009

RESUMO

Background: Chemotherapy with gemcitabine and nab-paclitaxel (gemcitabine/nab-paclitaxel) is recommended for unresectable pancreatic cancer. However, the therapeutic efficacy is attenuated by the antitumor agent-induced activation of nuclear factor-κB (NF-κB). Thalidomide inhibits NF-κB activation, therefore, we hypothesized that pomalidomide, a third-generation IMiD, would also inhibit NF-κB activation and enhance the antitumor effects of gemcitabine/nab-paclitaxel. Methods: In vitro, we assessed NF-κB activity and apoptosis in response to pomalidomide alone, gemcitabine/nab-paclitaxel, or combination of pomalidomide and gemcitabine/nab-paclitaxel in human pancreatic cancer cell lines (PANC-1 and MIA PaCa-2). In vivo, we established orthotopic model and the animals were treated with oral pomalidomide and injection of gemcitabine/nab-paclitaxel. Results: In pomalidomide and gemcitabine/nab-paclitaxel group, gemcitabine/nab-paclitaxel-induced NF-κB activation was inhibited and apoptosis was enhanced in comparison with those in the other groups both in vitro and in vivo. Especially, this study revealed for the first time that pomalidomide enhances p53 on pancreatic cancer cells. The tumor growth in the pomalidomide and gemcitabine/nab-paclitaxel group was significantly slower than that in the gemcitabine/nab-paclitaxel group. Moreover, pomalidomide induced G0/G1 cell cycle arrest and suppressed angiogenesis. Conclusions: Pomalidomide enhanced the antitumor effect of gemcitabine/nab-paclitaxel by inhibition of NF-κB activation. This combination regimen would be a novel strategy for treating pancreatic cancer.

19.
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
20.
Anticancer Res ; 38(4): 2369-2375, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29599363

RESUMO

BACKGROUND/AIM: Omega-3 fatty acids may improve cancer cachexia, but only in patients with pancreatic and bile duct cancer. Patients with pancreatic cancer commonly suffer from exocrine pancreatic insufficiency, and the ingestion of digestive enzyme supplements may improve absorption. PATIENTS AND METHODS: Racol®, an enteral nutrient formulated with omega-3 fatty acids, was administered to patients with unresectable pancreatic and bile duct cancer. The skeletal muscle mass and blood test data were taken pre-administration and at 4 and 8 weeks after. Patients with pancreatic cancer were given the digestive enzyme supplement LipaCreon® from the fifth week after the start of administration. RESULTS: In all 27 patients, skeletal muscle mass was significantly increased at both 4 and 8 weeks after the start of administration versus pre-administration (p=0.006, p=0.002, respectively). CONCLUSION: Omega-3 fatty acid supplementation in patients with unresectable pancreatic and bile duct cancer may improve cancer cachexia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/dietoterapia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Neoplasias Pancreáticas/dietoterapia , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Neoplasias dos Ductos Biliares/patologia , Caquexia/prevenção & controle , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Suplementos Nutricionais , Combinação de Medicamentos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Apoio Nutricional/métodos , Compostos Organoplatínicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Piridinas/uso terapêutico , Tegafur/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA