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• W2924865629 abstract "Performing a meta-analysis of 19 cohort studies that included 1660 patients, Corral et al1Corral J.E. et al.Clin Gastroenterol Hepatol. 2019; 17: 41-53Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar recently evaluated the effectiveness of screening in families at risk for developing pancreatic cancer. A total of 59 (3.5%) high-risk lesions were found, including 43 pancreatic cancers and 16 high-risk precursor lesions (ie, high-grade pancreatic intraepithelial neoplasia [PanIN] or cystic lesions), and the authors calculated an incidence rate for high-risk lesions of 0.47 per 100 patient-years. A total of 257 (15%) patients underwent pancreatic surgery for a suspected lesion. We would like to revisit the outcomes of 2 large studies that were not included in this meta-analysis. In a multicenter European study, published in 2016, we evaluated the results of screening in a large cohort of individuals at high risk for familial pancreatic cancer (FPC), including carriers of a CDKN2A mutation.2Vasen H. et al.J Clin Oncol. 2016; 34: 2010-2019Crossref PubMed Scopus (219) Google Scholar. Screening of 214 individuals with FPC, with a mean follow-up of 34 months, identified only 1 (0.47%) patient with pancreatic cancer. Thirteen patients underwent surgery due to a cystic lesion, 4 (1.9%) of whom harbored high-risk lesions. Screening of 178 Dutch CDKN2A mutation carriers, with a mean follow-up time of 53 months, detected pancreatic cancer in 13 (7.3%) patients but no high-risk precursor lesions (PanIN3 or high-grade intraductal papillary mucinous neoplasm) were found. The resection rate was 75% and the 5-year survival rate was 24%. In a subsequent study from the same centers, we evaluated the age at detection of high-risk lesions in 253 individuals from mainly FPC families (median follow-up 28 months).3Bartsch D.K. et al.Gut. 2016; 65: 1314-1321Crossref PubMed Scopus (57) Google Scholar A total of 21 individuals underwent surgery and a relevant lesion was found in 6 (2.4%) individuals (2 pancreatic ductal adenocarcinomas, 3 PanIN3s, and 1 high-grade intraductal papillary mucinous neoplasm). Because no high-risk lesions were detected below 50 years of age, we recommend that screening in FPC commences at this age. Corral et al1Corral J.E. et al.Clin Gastroenterol Hepatol. 2019; 17: 41-53Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar calculated that 135 individuals needed to be screened to identify 1 individual with a high-risk lesion, the number varying from 250 patients in the case of a BRCA1 or BRCA2 mutation to 51 patients in the case of a CDKN2A mutation. These numbers clearly indicate that large groups of individuals would have to participate in an intensive and burdensome screening program. Moreover, as only 59 of 257 operated patients had a high-risk lesion, 198 patients underwent major pancreatic surgery unnecessarily, a procedure associated with morbidity and mortality rates of up to 40% and 2%–4%, respectively.1Corral J.E. et al.Clin Gastroenterol Hepatol. 2019; 17: 41-53Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Extrapolating these figures, between 4 and 8 individuals may have died due to surgical complications. In view of these considerations, surveillance of the pancreas remains a potentially dangerous form of screening that should be limited to expert centers and only performed in a research setting.4Vasen H.F.A. Fam Cancer. 2018; 17: 1-3Crossref PubMed Scopus (6) Google Scholar In addition, the program should only be offered to individuals with a substantially increased risk of pancreatic cancer. This was shown in a simulation study by Pandharipande et al,5Pandharipande P.V. et al.EBioMedicine. 2015; 2: 1980-1986Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar who found that screening of low-risk individuals was associated with a reduced life expectancy, an outcome attributed to the increased discovery of insignificant lesions and subsequent unnecessary surgical intervention. In this regard, it is problematic that the risk of pancreatic cancer is unknown for most of the gene defects associated with pancreatic cancer (eg, BRCA1, PALB2, MMR genes, ATM). Current recommendations on which individuals to screen are therefore only based on the expert opinion of the Pancreas Cancer Screening Consortium, see the editorial by Hart and Chari,6Hart P.A. et al.Clin Gastroenterol Hepatol. 2019; 17: 36-38Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar and not on objectively established risk. To facilitate the identification of gene defects associated with pancreatic cancer development, universal testing using gene panels is currently recommended for all new pancreatic cancers.7Syngal S. et al.JAMA. 2018; 319: 2383-2385Crossref PubMed Scopus (7) Google Scholar However, before initiating the large scale testing of all pancreatic cancers, evaluation of pancreatic cancer risk in carriers of various mutations is urgently needed to permit appropriate selection of individuals for screening. In an editorial on the Corral et al1Corral J.E. et al.Clin Gastroenterol Hepatol. 2019; 17: 41-53Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar study, Hart and Chari6Hart P.A. et al.Clin Gastroenterol Hepatol. 2019; 17: 36-38Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar discussed the challenges of early detection of pancreatic cancer, referring to the Chinese proverb: “the journey of a thousand miles starts with one step.” They also stated that “studies evaluating those at increased risk for pancreatic cancer because of a family history, genetic profile, and new onset diabetes represent multiple steps in the right direction.” We would like to suggest that these steps are taken in the correct order. Diagnostic Yield From Screening Asymptomatic Individuals at High Risk for Pancreatic Cancer: A Meta-analysis of Cohort StudiesClinical Gastroenterology and HepatologyVol. 17Issue 1PreviewThere have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 17Issue 9PreviewWe thank Professor Vasen and colleagues for their thoughtful commentary on our article. Indeed, we share their concerns that invasive screening tests are largely inappropriate for low-risk populations because of the relatively low yield and positive predictive values. Full-Text PDF" @default.
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• W2924865629 title "Screening of Individuals at High Risk for Pancreatic Cancer" @default.
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