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9.
Br J Cancer ; 108(7): 1488-94, 2013 Apr 16.
Article in English | MEDLINE | ID: mdl-23492684

ABSTRACT

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.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Deoxycytidine/analogs & derivatives , Equilibrative Nucleoside Transporter 1/metabolism , Pancreatic Neoplasms/drug therapy , Receptors, Notch/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Deoxycytidine/therapeutic use , Equilibrative Nucleoside Transporter 1/genetics , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptor, Notch3 , Receptors, Notch/genetics , Retrospective Studies , Gemcitabine
12.
Endoscopy ; 41(11): 959-64, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19802775

ABSTRACT

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.


Subject(s)
Bile Duct Neoplasms/pathology , Carcinoma in Situ/pathology , Cholangiography , Endoscopy, Digestive System , Aged , Aged, 80 and over , Bile Duct Neoplasms/diagnostic imaging , Carcinoma in Situ/diagnostic imaging , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Retrospective Studies
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