Elisabeth Maurer, Bettina Lehman, Elvira Matthäi, Ulrike Denzer, Jens Figiel, Moritz Jesinghaus, Emily P Slater, Ulrich Stefenelli, Thomas M Gress, Detlef K Bartsch
{"title":"胰腺癌筛查对具有易感性种系基因变异的高危人群有效，但对基因变异阴性的家族性胰腺癌家族无效。","authors":"Elisabeth Maurer, Bettina Lehman, Elvira Matthäi, Ulrike Denzer, Jens Figiel, Moritz Jesinghaus, Emily P Slater, Ulrich Stefenelli, Thomas M Gress, Detlef K Bartsch","doi":"10.1002/ueg2.12631","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Design: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1211-1221"},"PeriodicalIF":5.8000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578844/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant-negative familial pancreatic cancer families.\",\"authors\":\"Elisabeth Maurer, Bettina Lehman, Elvira Matthäi, Ulrike Denzer, Jens Figiel, Moritz Jesinghaus, Emily P Slater, Ulrich Stefenelli, Thomas M Gress, Detlef K Bartsch\",\"doi\":\"10.1002/ueg2.12631\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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).</p><p><strong>Design: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":23444,\"journal\":{\"name\":\"United European Gastroenterology Journal\",\"volume\":\" \",\"pages\":\"1211-1221\"},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578844/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"United European Gastroenterology Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/ueg2.12631\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"United European Gastroenterology Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ueg2.12631","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的评估胰腺癌筛查对家族性胰腺癌（FPC）家族高危个体（IAR）的诊断率，以及是否存在易患胰腺腺癌（PDAC）的致病基因变异：设计：20 年间，德国全国胰腺癌病例收集中心的一项前瞻性筛查计划对来自胰腺癌家族的 IAR 进行了登记，包括磁共振成像（MRI）和内镜超声检查（EUS）。对重要胰腺病变（如 PDAC、高级别胰腺上皮内瘤变（PanIN3）和导管内乳头状粘液性瘤变（IPMN）伴高级别发育不良）的诊断率进行了分析。对致病变异携带者和变异阴性 IAR 的筛查结果进行了比较：对337名IAR，包括74名（22%）变异携带者和263名变异阴性FPC家族的IAR（平均年龄49岁；标准差[SD] + 8.9）进行了64个月（SD + 55）的随访。IAR接受了5.1（标度+3.9）次筛查，其中核磁共振成像1733次（5.1，标度+3.9/IAR），EUS 728次（2.2，标度+1.7/IAR）。在 12 例（4%）病例中发现了明显的胰腺病变，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 例在术后平均 27 个月后死亡，1 例 IAR 在术后 31 个月后仍存活且无病变迹象。变异携带者的重大病变诊断率为 13.5%（10/74），而变异阴性 FPC 家族的 IAR 诊断率为 0.8%（2/263）（P 结论：变异携带者的重大病变诊断率似乎证明了 PDAC 的合理性：在PDAC易感基因中存在致病性种系变异的FPC家族的IAR中，而在变异阴性家族的IAR中，诊断率似乎证明了PDAC筛查的合理性。
Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant-negative familial pancreatic cancer families.
Objective: 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).
Design: 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.
Results: 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%).
Conclusion: 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.
期刊介绍：
United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
