评估胰腺癌筛查对家族性胰腺癌 (FPC) 家族的高危个体 (IAR) 是否存在易患胰腺癌 (PDAC) 的致病性种系变异的诊断效果。在 20 年期间，IAR来自 FPC 家庭的患者参加了德国 FPC 国家病例收集的前瞻性筛查计划，包括磁共振成像 (MRI) 和内窥镜超声 (EUS)。分析了显着胰腺病变的诊断率，例如 PDAC、高级胰腺上皮内瘤变 (PanIN3) 和伴有高度不典型增生的导管内乳头状粘液瘤 (IPMN)。对致病性变异携带者和变异阴性 IAR 的筛查结果进行了比较。对 337 个 IAR（包括 74 个（22%）变异携带者）和 263 个变异阴性 FPC 家族的 IAR（平均年龄 49 岁；标准差 [SD] 8.9）进行了跟踪64 (SD 55) 个月。 IAR 接受了 5.1 (SD 3.9) 次筛查访视，其中包括 1733 次 MRI（每个 IAR 5.1，SD 3.9）和 728 次 EUS（每个 IAR 2.2，SD 1.7）。在 12 例（4%）病例中，检测到明显的胰腺病变，包括 4 例 PDAC、3 例 PanIN3 和 5 例高级别 IPMN。 4 例患有 PDAC 的 IAR 中，有 3 例在平均术后 27 个月后死亡，1 例 IAR 在 31 个月后仍然存活，没有疾病证据。变异携带者显着病变的诊断率为 13.5% (10/74)，而变异阴性 FPC 家族 IAR 的诊断率为 0.8% (2/263) (p < 0.001)。 Logistic 回归分析显示，随着时间的推移，阴性变异状态几乎总是伴随着不存在显着病变，阴性预测值为 99.2% (95% CI 97.3%-99.9%)。诊断率似乎证明了 PDAC 筛查的合理性。 PDAC 易感基因中具有致病性种系变异的 FPC 家族的 IAR，而不是变异阴性家族的 IAR。© 2024 作者。 《联合欧洲胃肠病学杂志》由 Wiley periodicals LLC 代表联合欧洲胃肠病学出版。

To evaluate the diagnostic yield of pancreatic cancer screening in individuals at risk (IAR) from familial pancreatic cancer (FPC) families with respect to the presence or absence of pathogenic germline variants predisposing to pancreatic adenocarcinoma (PDAC).In a 20 years period, IAR from FPC families were enrolled in a prospective screening program of the national case collection for FPC of Germany, including magnet resonance imaging (MRI) and endoscopic ultrasound (EUS). The diagnostic yield was analyzed regarding significant pancreatic lesions such as PDAC, high-grade pancreatic-intraepithelial-neoplasia (PanIN3) and intraductal-papillary-mucinous-neoplasia (IPMN) with high-grade dysplasia. Screening results were compared between carriers of pathogenic variants and variant-negative IAR.337 IAR, including 74 (22%) variant-carriers and 263 IAR of variant-negative FPC families (mean age 49; standard deviation [SD] + 8.9) were followed 64 (SD + 55) months. IAR underwent 5.1 (SD + 3.9) screening visits with 1733 MRI (5.1,SD + 3.9 per IAR) and 728 EUS (2.2,SD + 1.7 per IAR). In 12 (4%) cases, significant pancreatic lesions were detected, including 4 PDAC, 3 PanIN3 and 5 high-grade IPMN. Three of 4 IAR with PDAC died after a mean of 27 months postoperatively, and one IAR is alive without evidence of disease after 31 months. The diagnostic yield for significant lesions was 13.5% (10/74) for variant carriers compared to 0.8% (2/263) for IAR of variant-negative FPC families (p < 0.001). Logistic regression analysis revealed that a negative variant status was almost always accompanied by the absence of a significant lesion over time with a negative predictive value of 99.2% (95% CI 97.3%-99.9%).The diagnostic yield seems to justify PDAC screening in IAR of FPC-families with pathogenic germline variants in PDAC predisposing genes, not in IAR of variant-negative families.© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.