Department of Visceral-, Thoracic- and Vascular Surgery, Philipps University Marburg, Marburg, Germany.
Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, Philipps University Marburg, Marburg, Germany.
United European Gastroenterol J. 2024 Nov;12(9):1211-1221. doi: 10.1002/ueg2.12631. Epub 2024 Jul 19.
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.
评估在具有致瘤性种系变异的家族性胰腺癌（FPC）家族的高危个体（IAR）中进行胰腺癌筛查的诊断收益，这些变异会导致胰腺腺癌（PDAC）。
在 20 年的时间里，德国国家 FPC 病例采集项目纳入了 FPC 家族的 IAR 进行前瞻性筛查，包括磁共振成像（MRI）和内镜超声检查（EUS）。分析了有意义的胰腺病变（如 PDAC、高级别胰腺上皮内瘤变（PanIN3）和导管内乳头状黏液性肿瘤（IPMN）伴高级别异型增生）的诊断收益。将携带致病性变异的 IAR 和变异阴性的 IAR 的筛查结果进行了比较。
337 名 IAR 纳入研究，其中 74 名（22%）为携带致病性变异的个体，263 名 IAR 的 FPC 家族为变异阴性（平均年龄 49；标准差 [SD] + 8.9），随访时间 64（SD + 55）个月。IAR 接受了 5.1（SD + 3.9）次筛查，其中 1733 次 MRI（SD + 3.9 次/IAR）和 728 次 EUS（SD + 1.7 次/IAR）。在 12 例（4%）中发现了有意义的胰腺病变，包括 4 例 PDAC、3 例 PanIN3 和 5 例高级别 IPMN。4 例 PDAC 中的 3 例 IAR 在术后平均 27 个月后死亡，1 例 IAR 在术后 31 个月时仍无疾病证据。携带致病性变异的 IAR 中显著病变的诊断收益为 13.5%（10/74），而变异阴性的 FPC 家族 IAR 的诊断收益为 0.8%（2/263）（p < 0.001）。逻辑回归分析显示，种系变异状态为阴性几乎总是意味着随着时间的推移不存在有意义的病变，阴性预测值为 99.2%（95%可信区间 97.3%-99.9%）。
在具有致瘤性种系变异的 FPC 家族的 IAR 中进行 PDAC 筛查似乎具有诊断收益，但在变异阴性的 FPC 家族的 IAR 中没有诊断收益。
