RESUMO
BACKGROUND: Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC. METHODS: The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription-polymerase chain reactions and examined for correlations with GEM sensitivity. RESULTS: The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively). CONCLUSION: hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Receptores Notch/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Desoxicitidina/uso terapêutico , Transportador Equilibrativo 1 de Nucleosídeo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptor Notch3 , Receptores Notch/genética , Estudos Retrospectivos , GencitabinaAssuntos
Doenças Autoimunes/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/diagnóstico , Imunoglobulina G/sangue , Mieloma Múltiplo/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico , Idoso de 80 Anos ou mais , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Biomarcadores Tumorais/imunologia , Biópsia , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Endossonografia , Feminino , Humanos , Imunoglobulina G/imunologia , Imuno-Histoquímica , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Pancreatite/sangue , Pancreatite/imunologia , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Regulação para CimaAssuntos
Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Regressão Neoplásica Espontânea , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Tomografia Computadorizada por Raios XAssuntos
Fístula Anastomótica/terapia , Nefropatias Diabéticas/cirurgia , Drenagem/métodos , Endoscopia/métodos , Ductos Pancreáticos , Complicações Pós-Operatórias/terapia , Uretra , Fístula Anastomótica/diagnóstico por imagem , Cistostomia/métodos , Duodeno/cirurgia , Feminino , Humanos , Transplante de Rim/métodos , Pessoa de Meia-Idade , Pâncreas/cirurgia , Transplante de Pâncreas/métodos , Ductos Pancreáticos/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagemRESUMO
BACKGROUND AND STUDY AIMS: Localized-type bile duct carcinoma (LBDC) is often accompanied by extensive intraepithelial tumor spread (ITS) of 2 cm or more, which makes radical resection more difficult. This retrospective case review compares the diagnostic accuracy of endoscopic retrograde cholangiography (ERC) and peroral cholangioscopy (POCS) to detect ITS beyond the visible LBDC. PATIENTS AND METHODS: Forty-four consecutive patients with LBDC diagnosed between April 2004 and October 2008 who underwent radical resection with histopathological analysis were included in this study. Extensive ITS was found histopathologically in one-third of the cases (32 %). The outcome parameters were the presence or absence of extensive ITS and the extent of extensive ITS proximal and distal to the main tumor. RESULTS: In six cases it was not possible to pass the cholangioscope through the tumor sites. ERC correctly identified the presence of extensive ITS in 11/14 cases and did not yield any false-positive results. The three cases in which ERC was negative were all correctly identified by POCS plus biopsy since the cholangioscope could be passed in all three cases. The extent of extensive ITS was correctly diagnosed by ERC alone, ERC with POCS, and ERC with POCS plus mapping biopsy in 22 %, 77 %, and 100 % of cases, respectively. CONCLUSIONS: The presence of extensive ITS was correctly detected in 80 % of cases by ERC alone. POCS with mapping biopsy provided perfect diagnostic accuracy not only of the presence or absence but also of the extent of extensive ITS. However, POCS has the limitation that the cholangioscope cannot be passed through the tumor sites in approximately 15 % of cases.