Early Detection of Sporadic Pancreatic Ductal Adenocarcinoma: Problems, Promise, and Prospects

2020 ◽  
Vol 172 (8) ◽  
pp. 558
Author(s):  
Suresh T. Chari ◽  
Ayush Sharma ◽  
Anirban Maitra
Keyword(s):  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma

scholarly journals New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e037267
Author(s):  
Dóra Illés ◽  
Emese Ivány ◽  
Gábor Holzinger ◽  
Klára Kosár ◽  
M Gordian Adam ◽  
...  
Keyword(s):  
High Risk ◽  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Symptoms ◽  
Risk Group ◽  
High Risk Group ◽  
Ductal Adenocarcinoma ◽  
Onset Diabetes ◽  
Dismal Prognosis ◽  
New Onset

IntroductionPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare.Methods and analysisThis is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19–9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM.Ethics and disseminationThe study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial.Trial registration numberClinicalTrials.gov NCT04164602

scholarly journals Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis

EBioMedicine ◽  
2022 ◽  
Vol 75 ◽  
pp. 103797
Author(s):  
Neus Martínez-Bosch ◽  
Helena Cristóbal ◽  
Mar Iglesias ◽  
Meritxell Gironella ◽  
Luis Barranco ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Blood Marker

Mo1344 DEVELOPMENT OF A NOVEL CIRCULAR RNA-BASED, NONINVASIVE LIQUID BIOPSY ASSAY FOR THE EARLY DETECTION OF PANCREATIC DUCTAL ADENOCARCINOMA

2020 ◽  
Vol 158 (6) ◽  
pp. S-857
Author(s):  
SOUVIK GHATAK ◽  
Satoshi Nishiwada ◽  
Eunsung Jun ◽  
Fuminori Sonohara ◽  
Yasuhiro Kodera ◽  
...  
Keyword(s):  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Liquid Biopsy ◽  
Circular Rna ◽  
Ductal Adenocarcinoma

scholarly journals Early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumour DNA

2019 ◽  
Vol 30 ◽  
pp. v261-v262 ◽  
Author(s):  
X.-D. Liu ◽  
H. Wu ◽  
Y. Li ◽  
X. Liu ◽  
Z. Zhang ◽  
...  
Keyword(s):  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Circulating Tumour Dna

scholarly journals Imaging-Based Subtypes of Pancreatic Ductal Adenocarcinoma Exhibit Differential Growth and Metabolic Patterns in the Pre-Diagnostic Period: Implications for Early Detection

2020 ◽  
Vol 10 ◽  
Author(s):  
Mohamed Zaid ◽  
Dalia Elganainy ◽  
Prashant Dogra ◽  
Annie Dai ◽  
Lauren Widmann ◽  
...  
Keyword(s):  
Growth Rate ◽  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cross Validation ◽  
Abdominal Fat ◽  
Metabolic Effects ◽  
Ct Scans ◽  
Ductal Adenocarcinoma ◽  
Tumor Growth Rate ◽  
Average Growth

BackgroundPreviously, we characterized subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed-tomography (CT) scans, whereby conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we hypothesized that these imaging-based subtypes would exhibit different growth-rates and distinctive metabolic effects in the period prior to PDAC diagnosis.Materials and methodsRetrospectively, we evaluated 55 patients who developed PDAC as a second primary cancer and underwent serial pre-diagnostic (T0) and diagnostic (T1) CT-scans. We scored the PDAC tumors into high and low delta on T1 and, serially, obtained the biaxial measurements of the pancreatic lesions (T0-T1). We used the Gompertz-function to model the growth-kinetics and estimate the tumor growth-rate constant (α) which was used for tumor binary classification, followed by cross-validation of the classifier accuracy. We used maximum-likelihood estimation to estimate initiation-time from a single cell (10-6 mm3) to a 10 mm3 tumor mass. Finally, we serially quantified the subcutaneous-abdominal-fat (SAF), visceral-abdominal-fat (VAF), and muscles volumes (cm3) on CT-scans, and recorded the change in blood glucose (BG) levels. T-test, likelihood-ratio, Cox proportional-hazards, and Kaplan-Meier were used for statistical analysis and p-value <0.05 was considered significant.ResultsCompared to high delta tumors, low delta tumors had significantly slower average growth-rate constants (0.024 month−1 vs. 0.088 month−1, p<0.0001) and longer average initiation-times (14 years vs. 5 years, p<0.0001). α demonstrated high accuracy (area under the curve (AUC)=0.85) in classifying the tumors into high and low delta, with an optimal cut-off of 0.034 month−1. Leave-one-out-cross-validation showed 80% accuracy in predicting the delta-class (AUC=0.84). High delta tumors exhibited accelerated SAF, VAF, and muscle wasting (p <0.001), and BG disturbance (p<0.01) compared to low delta tumors. Patients with low delta tumors had better PDAC-specific progression-free survival (log-rank, p<0.0001), earlier stage tumors (p=0.005), and higher likelihood to receive resection after PDAC diagnosis (p=0.008), compared to those with high delta tumors.ConclusionImaging-based subtypes of PDAC exhibit distinct growth, metabolic, and clinical profiles during the pre-diagnostic period. Our results suggest that heterogeneous disease biology may be an important consideration in early detection strategies for PDAC.

scholarly journals MicroRNA-21 Is Induced Early in Pancreatic Ductal Adenocarcinoma Precursor Lesions

2010 ◽  
Vol 56 (4) ◽  
pp. 603-612 ◽  
Author(s):  
Maël Chalret du Rieu ◽  
Jérôme Torrisani ◽  
Janick Selves ◽  
Talal Al Saati ◽  
Anny Souque ◽  
...  
Keyword(s):  
Early Detection ◽  
Mouse Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Early Event ◽  
Precursor Lesions ◽  
Tissue Samples ◽  
Ductal Cells

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has the poorest overall prognosis among gastrointestinal cancers; however, curative resection in early-stage PDAC greatly improves survival rates, indicating the importance of early detection. Because abnormal microRNA production is commonly detected in cancer, we investigated noninvasive precursor pancreatic intraepithelial neoplasia (PanIN) lesions for microRNA production as a potential early biomarker of PDAC. Methods: Pathologists identified and classified ductal lesions. We extracted total RNA from laser-capture microdissected PanIN tissue samples from a conditional KRAS(G12D) mouse model (n = 29) or of human origin (n = 38) (KRAS is v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). MicroRNA production was quantified by quantitative real-time PCR. Internal controls included 5S and U6 RNAs. Results: Production of microRNAs miR-21, miR-205, and miR-200 paralleled PanIN progression in the KRAS(G12D) mouse model, compared with microRNA production in samples of nonpathologic ducts. miR-21 demonstrated the highest relative concentrations in the precursor lesions. Interestingly, miR-205 and miR-21 up-regulation preceded phenotypic changes in the ducts. The production of microRNAs miR-21, miR-221, miR-222, and let-7a increased with human PanIN grade, with peak production occurring in hyperplastic PanIN-2/3 lesions. In situ hybridization analysis indicated miR-21 production to be concentrated in pathologic ductal cells. miR-21 production was regulated by KRAS(G12D) and epidermal growth factor receptor in PDAC-derived cell lines. Conclusions: Aberrant microRNA production is an early event in the development of PanIN. Our findings indicate that miR-21 warrants further investigation as a marker for early detection of PDAC.

scholarly journals Metabolomics based predictive classifier for early detection of pancreatic ductal adenocarcinoma

Oncotarget ◽  
2018 ◽  
Vol 9 (33) ◽  
pp. 23078-23090 ◽  
Author(s):  
Keith Unger ◽  
Khyati Y. Mehta ◽  
Prabhjit Kaur ◽  
Yiwen Wang ◽  
Smrithi S. Menon ◽  
...  
Keyword(s):  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma
Sign in / Sign up

Export Citation Format

Share Document