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Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma.

ABSTRACT: Epithelial cell adhesion molecule (EpCAM) has been used as surrogate marker for the quantification of circulating tumour cells (CTC). Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).From 48 patients with PDAC (40 resectable, 8 unresectable) and 10 patients with chronic pancreatitis undergoing pancreatectomy 10 ml of venous blood was drawn preoperatively (PB) and postoperatively (POB, day 1 (D1B), day 7 (D7B) and after 6 weeks (6WB). Of all patients undergoing pancreatectomy, 40 ml peritoneal lavage fluid was taken preoperatively and postoperatively. A real-time RT-PCR assay (TaqMan, ABI Prism 7700) was developed for the detection of EpCAM mRNA. To discriminate between EpCAM-positive and negative samples a cut-off was applied. Median postoperative follow-up was 24.0 months (range: 0.7-41.3).PB was EpCAM-positive+ in 25% of patients versus 65% of patients in POB (p < 0.0001). EpCAM+ was noted at D1B, D7B and 6WB was found in 28.6%, 23.1% and 23.5% of patients respectively. Preoperative peritoneal lavage fluid was EpCAM+ in 10.3% versus 53.8% of patients postoperatively (p < 0.0001). At none of the time-points, an association was found between EpCAM positivity in blood and/or peritoneal cavity and cancer-specific or disease-free survival. Also, no significant associations were found between clinicopathological variables and perioperative EpCAM positivity.Despite a significant increase in EpCAM counts in postoperative blood and peritoneal lavage fluid this was not associated with worse prognosis after pancreatectomy for PDAC.Clinicaltrials.gov NCT00495924.

SUBMITTER: Sergeant G

PROVIDER: S-EPMC3045357 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma.

Sergeant Gregory G Roskams Tania T van Pelt Jos J Houtmeyers François F Aerts Raymond R Topal Baki B

BMC cancer 20110131

<h4>Background</h4>Epithelial cell adhesion molecule (EpCAM) has been used as surrogate marker for the quantification of circulating tumour cells (CTC). Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).<h4>Methods</h4>From 48 patients with PDAC (40 resectable, 8 unresectable) and 10 patients with chronic pancreatitis undergoin ...[more]

PMID: 21281486

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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection.MethodsWe performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, n = 427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, n = 70) PDAC cohort to verify the conclusion.ResultsBoth the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC (p = 0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression (p = 0.011 and p = 0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, p = 0.017) and 1.596 (95% CI: 1.061-2.401, p = 0.025), respectively.ConclusionsMUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death.

Project description:Pancreatic ductal adenocarcinoma (PDA) is an extremely lethal malignancy arising from the pancreas. The treatment of PDA is complicated by ineffective treatments and a lack of biomarkers predictive of treatment success. We have designed a patient-derived organoid (PDO) based high-throughput drug screening assay to model treatment response to a variety of conventional and investigational treatments for PDA. Consecutive patients undergoing endoscopic ultrasound-guided fine-needle biopsy for tissue diagnosis of PDA at Rush University Medical Center were offered to participate in the study. Biopsies were immediately processed to develop organoids. Fifteen PDOs were screened for sensitivity to 18 compounds, including conventional PDA chemotherapies and FDA-approved investigational targeted therapies in cancer using Cell-titer GLO 3D (Promega) cell viability assay. The area under the curve (AUC) was calculated and normalized to the maximum area under the curve to generate a normalized AUC between 0 and 1. Molecular profiling of PDOs was conducted using RNA-seq. Human PDA transcriptomic was extracted from The Cancer Genome Atlas (TCGA). The drug response curves were reproducible. We observed variation in response to conventional therapies overall as well as among individual patients. There were distinct transcriptome signatures associated with response to the conventional chemotherapeutics in PDA. The transcriptomic profile of overall resistance to conventional therapies in our study was associated with poor survival in PDA patients in TCGA. Our pathway analysis for targeted drugs revealed a number of predictors of response associated with the mechanism of action of the tested drug. The multiplex organoid-based drug assay could be used in preclinical to inform patient stratification and therapeutic selection in PDA. When combined with omics data, ex vivo response to treatment could help identify gene signatures associated with response to novel therapies.

Project description:BACKGROUND AND AIMS: Pancreaticoduodenectomy (PD) is a major operative intervention performed most commonly for malignancy in the head of pancreas. The aim of this study was to evaluate the utilization of blood transfusion for PD and to determine whether this had prognostic significance in a subset of patients with pancreatic ductal adenocarcinoma (PDAC). MATERIAL AND METHODS: Data on blood transfusion requirement were retrospectively collected for patients undergoing PD from 1998 to 2005. Standard prognostic factors and survival data were also collected in patients with PDAC. RESULTS: One-hundred-and-seventy patients underwent PD. Seventy-six patients (45%) received transfusion. The median (interquartile range) number of units of red cell concentrate (RCC) transfused perioperatively (intraoperatively and within 24 h of surgery) was 1.5 (0.5-2.5). The median preoperative haemoglobin (Hb) was 126 g/dl. The median number of units of RCC transfused perioperatively in patients with Hb <126 g/dl was 2 (1-3); for those with Hb > or = 126 g/dl the median was 0 (0-1); p=0.003. Forty-nine patients who were resected for PDAC were subjected to survival analysis. Univariate and multivariate analyses showed that only posterior resection margin invasion was associated with an adverse outcome (margin positive 198 [143-470] days vs margin negative 398 [303-859] days; p=0.02). Perioperative RCC transfusion requirement was not a significant predictor of survival (transfusion 408 [214-769] days vs no transfusion 331 [217-391] days; p=0.18). Furthermore, RCC transfusion within 30 days of operation was not a significant predictor of poor survival (transfusion 331 [201-459] days vs no transfusion 317 [196-769] days; p=0.43). CONCLUSIONS: PD can be performed with a moderately low requirement for RCC transfusion; however, low preoperative haemoglobin is a predictor for the requirement of RCC transfusion. Administration of RCC transfusion does not appear to be a significant adverse prognostic factor in patients with resected PDAC.

Project description:BACKGROUND:It is unclear whether results from recent trials of resectable pancreatic ductal adenocarcinoma (PDAC) are generalizable to older patients, who are underrepresented. We aimed to evaluate outcomes of surgery and of neoadjuvant and adjuvant therapy in older patients with resectable PDAC. PATIENTS AND METHODS:We included patients aged ?65?years with upfront resectable PDAC from a prospectively maintained pancreatic cancer registry from 2007 to 2016. Patients were stratified into ages 65-75 and 75+ years. Overall survival (OS) was assessed in treatment comparisons: (A) surgery (n =?636) versus nonsurgical (n =?178), (B) neoadjuvant therapy (n =?139) versus upfront surgery (n =?497), and (C) adjuvant therapy (n =?379) versus surgery alone (n =?118). We compared neoadjuvant (n =?139) versus adjuvant therapy (n =?379) in an exploratory analysis. RESULTS:Nine hundred and three patients had a median age of 73.7 (range, 65-96.6) years. Median OS was 26.6 versus 11.9 months (adjusted hazard ratio [HRadj ], 0.4; 95% confidence interval [CI], 0.31-0.52; p < .001) in Comparison A groups, 30.7 versus 25.8 months (HRadj , 0.69; 95% CI, 0.49-0.96; p = .03) in Comparison B groups, and 26.9 versus 17.4 months (HRadj , 0.62; 95% CI, 0.44-0.88; p = .008) in Comparison C groups, respectively. OS benefit in these treatment comparisons was present in age group 75+ with HRadj 0.24 (95% CI, 0.16-0.36; p < .001) in Comparison A and HRadj 0.52 (95% CI, 0.27-1; p = .049) in Comparison B, but not in Comparison C with HRadj 0.68 (95% CI, 0.43-1.08; p = .1). Statistically comparable median OS of patients who received neoadjuvant or adjuvant therapy stratified by age groups was observed. CONCLUSION:Older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. IMPLICATIONS FOR PRACTICE:Older patients with resectable pancreatic ductal adenocarcinoma (PDAC) in general are underrepresented in large clinical trials and less well studied in terms of the role of surgery, neoadjuvant therapy, and adjuvant therapy. This study collected data on older patients with resectable PDAC from a prospectively maintained single-institutional pancreatic cancer registry of a tertiary referral center from 2007 to 2016. It was found that, with multidisciplinary evaluation, older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. These results are of substantial importance to practitioners who treat older patients, who are traditionally underrepresented in most clinical trials.

Dataset Information

Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma.

Publications

Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma.

Similar Datasets

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