Dataset Information

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

ABSTRACT: BACKGROUND AND AIMS:Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis (CP) changes on EUS. The objective of this study was to determine whether CP changes were more common in high-risk individuals (HRIs) than in control subjects and whether these changes differed among higher-risk subsets of HRIs. METHODS:HRIs and control subjects were identified from an endoscopy database. HRIs were defined as having predisposing mutations or a family history (FH) of pancreatic ductal adenocarcinoma. HRIs were classified as vHRIs who met Cancer of the Pancreas Screening (CAPS) criteria for high risk and mHRIs who did not. Multivariable logistic regression was used to adjust for confounders and CP risk factors. RESULTS:Sixty-five HRIs (44 vHRIs, 21 mHRIs) and 118 control subjects were included. HRIs were included for FH (25), Lynch syndrome (5), Peutz-Jeghers syndrome (2), and mutations in BRCA1/2 (26), PALB2 (3), ATM (3), and CDKN2A (1). After adjustment for relevant variables, HRIs were 16 times more likely to exhibit 3 or more CP changes than control subjects (95% confidence interval, 2.6-97.0; P = .003). HRIs were also more likely to have hypoechoic foci (odds ratio, 8.0; 95% confidence interval, 1.9-32.9; P = .004). vHRIs and mHRIs did not differ in frequency of 3 or more CP changes on EUS. CONCLUSIONS:HRIs were more likely to exhibit CP changes and hypoechoic foci on EUS compared with control subjects. HRIs with these findings may require closer surveillance. HRIs who did or did not meet CAPS criteria did not differ with regard to CP findings, supporting a more inclusive approach to screening.

SUBMITTER: Thiruvengadam SS

PROVIDER: S-EPMC6589432 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Thiruvengadam Sushrut S SS Chuang Judith J Huang Robert R Girotra Mohit M Park Walter G WG

Gastrointestinal endoscopy 20180824 4

<h4>Background and aims</h4>Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis (CP) changes on EUS. The objective of this study was to determine whether CP changes were more common in high-risk individuals (HRIs) than in control subjects and whether these changes differed among higher-risk subsets of HRIs.<h4>Methods</h4>HRIs and control subjects were identified from an endoscopy database. HRIs were defined as having predisposing mutations or a family history (FH) of pa ...[more]

PMID: 30145314

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive stroma being also present in chronic pancreatitis (CP). Using immunohistochemistry, the stroma of CP and PDAC was comprehensively analyzed and correlated with epithelial/carcinoma-related alterations and clinicopathological patient characteristics. While there were no significant differences between CP and PDAC regarding the distribution of CD3+ T cells and ?-SMA+ fibroblasts, proportions of CD4+ and CD8+ T cells were significantly lower and numbers of CD25+(CD4+) and FoxP3+(CD4+) regulatory T cells were greater in PDAC compared with CP. Macrophages were more prevalent in CP, but localized more closely to carcinoma cells in PDAC, as were ??-T cells. Duct-related FoxP3 and L1CAM expression increased from CP to PDAC, while vimentin expression was similarly abundant in both diseases. Moreover, stromal and epithelial compartments of well-differentiated tumors and CPs shared considerable similarities, while moderately and poorly differentiated tumors significantly differed from CP tissues. Analysis of 27 parameters within each pancreatic disease revealed a significant correlation of i) CD4+ and FoxP3+CD4+ T cells with FoxP3 expression in PDAC cells, ii) ?-SMA+ fibroblasts with L1CAM expression and proliferation in PDAC cells, iii) CD3 and CD8 expression with ??-TCR expression in both pancreatic diseases and iv) CD68+ and CD163+ macrophages with vimentin expression in PDAC cells. High expression of FoxP3, vimentin and L1CAM in PDAC cells as well as a tumor-related localization of macrophages each tended to correlate with higher tumor grade. Multivariate survival analysis revealed a younger age at time of surgery as a positive prognostic marker for PDAC patients with the most frequently operated disease stage T3N1M0. Overall this study identified several interrelationships between stroma and epithelial/carcinoma cells in PDACs but also in CP, which in light of previous experimental data strongly support the view that the inflammatory stroma contributes to malignancy-associated alterations already in precursor cells during CP.

Project description:BackgroundThe differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined.MethodsIn this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients.ResultsThe linear model from the differentially expressed blood small EV miR-95-3p divided by miR-26b-5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19-9 (CA19-9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR-95-3p was associated with a "consequence" of "cancer" and miR-26b-5p as a "cause" of "pancreatitis." A subgroup analysis revealed that blood small EV miR-335-5p/miR-340-5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020).ConclusionsThis study indicated that blood small EV miR-95-3p/miR-26b-5p and its combination with serum levels of CA19-9 could separate PDAC from CP, and miR-335-5p/miR-340-5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC.

Project description:BackgroundIt is difficult to identify pancreatic ductal adenocarcinoma (PDAC) and mass-forming chronic pancreatitis (MFCP) lesions through conventional CT or MR examination. As an innovative image analysis method, radiomics may possess potential clinical value in identifying PDAC and MFCP. To develop and validate radiomics models derived from multiparametric MRI to distinguish pancreatic ductal adenocarcinoma (PDAC) and mass-forming chronic pancreatitis (MFCP) lesions.MethodsThis retrospective study included 119 patients from two independent institutions. Patients from one institution were used as the training cohort (51 patients with PDAC and 13 patients with MFCP), and patients from the other institution were used as the testing cohort (45 patients with PDAC and 10 patients with MFCP). All the patients had pathologically confirmed results, and preoperative MRI was performed. Four feature sets were extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and the artery (A) and portal (P) phases of dynamic contrast-enhanced MRI, and the corresponding radiomics models were established. Several clinical characteristics were used to discriminate PDAC and MFCP lesions, and clinical model was established. The results of radiologists' evaluation were compared with pathology and radiomics models. Univariate analysis and the least absolute shrinkage and selection operator algorithm were performed for feature selection, and a support vector machine was used for classification. The receiver operating characteristic (ROC) curve was applied to assess the model discrimination.ResultsThe areas under the ROC curves (AUCs) for the T1WI, T2WI, A and, P and clinical models were 0.893, 0.911, 0.958, 0.997 and 0.516 in the primary cohort, and 0.882, 0.902, 0.920, 0.962 and 0.649 in the validation cohort, respectively. All radiomics models performed better than clinical model and radiologists' evaluation both in the training and testing cohorts by comparing the AUC of various models, all P<0.050. Good calibration was achieved.ConclusionsThe radiomics models based on multiparametric MRI have the potential ability to classify PDAC and MFCP lesions.

Dataset Information

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

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

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