Chronic pancreatitis changes in high-risk individuals for pancreatic ductal adenocarcinoma

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

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Exosome‐encapsulated microRNA‐4525, microRNA‐451a and microRNA‐21 in portal vein blood is a high‐sensitive liquid biomarker for the selection of high‐risk pancreatic ductal adenocarcinoma patients

Journal of Hepato-Biliary-Pancreatic Sciences ◽

10.1002/jhbp.601 ◽

2019 ◽

Vol 26 (2) ◽

pp. 63-72 ◽

Cited By ~ 7

Author(s):

Sachiyo Kawamura ◽

Hisae Iinuma ◽

Keita Wada ◽

Kunihiko Takahashi ◽

Shunryo Minezaki ◽

...

Keyword(s):

High Risk ◽

Portal Vein ◽

Pancreatic Ductal Adenocarcinoma ◽

Ductal Adenocarcinoma ◽

Selection Of

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Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.728062 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongjie Chen ◽

Hui Huang ◽

Longjun Zang ◽

Wenzhe Gao ◽

Hongwei Zhu ◽

...

Keyword(s):

High Risk ◽

Pancreatic Ductal Adenocarcinoma ◽

Risk Score ◽

Cox Regression ◽

Pearson Correlation ◽

Risk Groups ◽

Low Risk ◽

Ductal Adenocarcinoma ◽

Prognostic Signature ◽

Score Model

We aim to construct a hypoxia- and immune-associated risk score model to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). By unsupervised consensus clustering algorithms, we generate two different hypoxia clusters. Then, we screened out 682 hypoxia-associated and 528 immune-associated PDAC differentially expressed genes (DEGs) of PDAC using Pearson correlation analysis based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression project (GTEx) dataset. Seven hypoxia and immune-associated signature genes (S100A16, PPP3CA, SEMA3C, PLAU, IL18, GDF11, and NR0B1) were identified to construct a risk score model using the Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, which stratified patients into high- and low-risk groups and were further validated in the GEO and ICGC cohort. Patients in the low-risk group showed superior overall survival (OS) to their high-risk counterparts (p < 0.05). Moreover, it was suggested by multivariate Cox regression that our constructed hypoxia-associated and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p < 0.001). By CIBERSORT and ESTIMATE algorithms, we discovered that patients in high-risk groups had lower immune score, stromal score, and immune checkpoint expression such as PD-L1, and different immunocyte infiltration states compared with those low-risk patients. The mutation spectrum also differs between high- and low-risk groups. To sum up, our hypoxia- and immune-associated prognostic signature can be used as an approach to stratify the risk of PDAC.

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Preoperative Score to Stratify Recurrence Risk After Curative Resection of Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Cohort Study

10.21203/rs.3.rs-697919/v1 ◽

2021 ◽

Author(s):

Yu Jiang ◽

SIYI Zou ◽

Weishen Wang ◽

Haoda Chen ◽

Qian Zhan ◽

...

Keyword(s):

High Risk ◽

Pancreatic Ductal Adenocarcinoma ◽

Prognostic Score ◽

Multidisciplinary Treatment ◽

Multivariable Analysis ◽

Disease Free Survival ◽

Ductal Adenocarcinoma ◽

Final Model ◽

Significant Difference ◽

Risk Patients

Abstract Background: Oncological survival after operation of resectable pancreatic ductal adenocarcinoma (R-PDAC) is variable depending on various factors. Preoperative risk stratification could guide decision-making in multidisciplinary treatment concepts. We develop and validate a prognostic score for disease-free survival (DFS) in R-PDAC to solve this issue.Methods: 421 R-PDAC patients between January 2012 and December 2015 were enrolled. Performance of the final model was evaluated with respect to discrimination, calibration and clinical usefulness. A prognostic score based on the final model was developed, and external validated in 290 patients.Results: On multivariable analysis, age, tumor size, carbohydrate antigen (CA)19-9, CA125, lymphocyte-monocyte ratio, and systemic-immune-inflammation index were independently associated with DFS. Final model had acceptable calibration, discrimination and internal validity. The prognostic score could delineate low- and high-risk groups with median DFS of 19.6 and 10.1 months (P<0.0001). Tumors in high-risk group exhibited more aggressive pathobiological behaviors. Additionally, at 1-year follow-up, the restricted mean survival time was longer with adjuvant chemotherapy than those without in low-risk patients. However, no significant difference was detected in high-risk patients.Discussion: The prognostic score could accurately predict DFS preoperatively in R-PDAC patients and provide reference for risk-adapted strategies formulation for R-PDAC management in the future.

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