BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for e...BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for early cancer detection.Endoscopic ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion characterization.While no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.AIM To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by EUS.METHODS This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCL,20 individuals with HR,and 20 patients with NLOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,Portugal.All patients provided written informed consent.EUS and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ELISA were performed in all subjects.EUS-guided tissue acquisition was done whenever necessary.For statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was used.All graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESULTS Half of MCLs harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NLOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCL[99.4%,interquartile range(IQR):94.9%-99.8%],HR(82.0%,IQR:28.9%-98.2%),NLOD(12.6%,IQR:5.2展开更多
基金Supported by Guilherme Macedo team was supported by the Portuguese Society of Digestive Endoscopy(SPED)2017 Research Grant,No.SG/CHSJ-A2017Norte Portugal Regional Programme(NORTE 2020)under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund(ERDF)to Sonia A Melo,No.NORTE-01-0145-FEDER-000029+1 种基金National Funds through Foundation for Science and Technology(FCT)to Sonia A Melo,No.POCI-01-0145-FEDER-32189Foundation for Science and Technology(FCT)to Bárbara Adem and Ines A Batista,No.PD/BD/135546/2018 and No.SFRH/BD/144854/2019.
文摘BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for early cancer detection.Endoscopic ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion characterization.While no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.AIM To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by EUS.METHODS This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCL,20 individuals with HR,and 20 patients with NLOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,Portugal.All patients provided written informed consent.EUS and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ELISA were performed in all subjects.EUS-guided tissue acquisition was done whenever necessary.For statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was used.All graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESULTS Half of MCLs harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NLOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCL[99.4%,interquartile range(IQR):94.9%-99.8%],HR(82.0%,IQR:28.9%-98.2%),NLOD(12.6%,IQR:5.2
