RESUMEN
BACKGROUND: Pancreatic cancer screening is recommended to individuals at risk (IAR) of familial pancreatic cancer (FPC) families, but little is known about the acceptance of such screening programs. Thus, the acceptance and psychological aspects of a controlled FPC screening program was evaluated. METHODS: IAR of FPC families underwent comprehensive counseling by a geneticist and pancreatologist prior to the proposed screening. Participating IAR, IAR who discontinued screening and IAR who never participated in the screening program were invited to complete questionnaires to assess the motivation for participating in surveillance, cancer worries, structural distress and experiences with participation. Questionnaires were completed anonymously to receive most accurate answers. RESULTS: Of 286 IAR to whom pancreatic ductal adenocarcinoma (PDAC) screening was recommended, 139 (48.6%) IAR regularly participated (group 1), 49 (17.1%) IAR (group 2) discontinued screening after median 1 (1-10) screening visits and 98 (34.2%) IAR (group 3) never underwent screening. The overall response rate of questionnaires was 67% (189/286) with rates of 100% (139 of 139 IAR), 49% (29 of 49 IAR) and 23.4% (23 of 98 IAR) for groups 1, 2 and 3, respectively. At least 93% of IAR felt adequately informed about the screening program after initial counseling. However, only 38.8% received knowledge of or the recommendation for PDAC screening by physicians. The reported cancer-related distress and the fear of investigations were highest in group 1, but acceptably low in all three groups. The main reasons to discontinue or not to participate in screening were the time efforts and travel costs (groups 2 and 3 48,7%). CONCLUSION: Less than 50% of IAR regularly participate in a proposed PDAC screening program, although the associated psychological burden is quite low. Physicians should be educated about high risk PDAC groups and screening recommendations. Time and travel efforts must be reduced to encourage more IAR to participate in a recommended screening.
RESUMEN
Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates for screening. Unfortunately, neither reliable imaging modalities nor biomarkers are available to detect high-grade precursor lesions or early cancer. Circulating levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma (PDAC, n = 50), FPC (n = 20), chronic pancreatitis (n = 10), IAR with relevant precursor lesions (n = 11) or non-relevant lesions (n = 5), 20 controls, and IAR with (n = 51) or without (n = 51) lesions on pancreatic imaging. In addition, corresponding duodenal juice samples were analyzed for Glypican-1 (n = 144) enrichment and KRAS mutations (n = 123). The panel miR-196b/LCN2/TIMP1 could distinguish high-grade lesions and stage I PDAC from controls with absolute specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes and duodenal juice was not diagnostic. KRAS mutations in duodenal juice were detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1 levels (p = 0.0007) and KRAS mutations in duodenal juice (p = 0.0004) significantly more often than IAR without imaging lesions. The combination miR-196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high-grade PDAC precursor lesions in IAR of FPC families.