Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Gastroenterology. 2020 Jan;158(1):226-237.e5. doi: 10.1053/j.gastro.2019.08.032. Epub 2019 Aug 29.
BACKGROUND & AIMS: Long-term outcomes of patients with branch-duct intraductal papillary mucinous neoplasms (IPMNs), particularly those after 5 years of surveillance, have not been fully evaluated in large studies. We analyzed incidences of IPMN-derived carcinoma and concomitant ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]) over 20 years in a large population of patients.
We identified 1404 consecutive patients (52% women; mean age, 67.5 years) with a diagnosis of branch-duct IPMN, from 1994 through 2017, at the University of Tokyo in Japan. Using a competing risk analysis, we estimated cumulative incidence of pancreatic carcinoma, overall and by carcinoma type. We used competing risks proportional hazards models to estimate subdistribution hazard ratios (SHRs) for incidences of carcinomas. To differentiate IPMN-derived and concomitant carcinomas, we collected genomic DNA from available paired samples of IPMNs and carcinomas and detected mutations in GNAS and KRAS by polymerase chain reaction and pyrosequencing.
During 9231 person-years of follow-up, we identified 68 patients with pancreatic carcinomas (38 patients with IPMN-derived carcinomas and 30 patients with concomitant PDACs); the overall incidence rates were 3.3%, 6.6%, and 15.0% at 5, 10, and 15 years, respectively. Among 804 patients followed more than 5 years, overall cumulative incidence rates of pancreatic carcinoma were 3.5% at 10 years and 12.0% at 15 years from the initial diagnosis. The size of the IPMN and the diameter of the main pancreatic duct associated with incidence of IPMN-derived carcinoma (SHR 1.85; 95% confidence interval 1.38-2.48 for a 10-mm increase in the IPMN size and SHR 1.56; 95% confidence interval 1.33-1.83 for a 1-mm increase in the main pancreatic duct diameter) but not with incidence of concomitant PDAC.
In a large long-term study of patients with branch-duct IPMNs, we found the 5-year incidence rate of pancreatic malignancy to be 3.3%, reaching 15.0% at 15 years after IPMN diagnosis. We observed heterogeneous risk factor profiles between IPMN-derived and concomitant carcinomas.
在大型研究中，尚未充分评估长期随访的分支胰管内乳头状黏液性肿瘤（IPMN）患者，尤其是随访 5 年以上患者的结局。我们分析了在日本东京大学的一个大型患者人群中，20 多年来分支胰管 IPMN 患者发生 IPMN 相关性癌和同时性导管腺癌（胰腺导管腺癌[PDAC]）的发生率。
我们从 1994 年至 2017 年，在日本东京大学识别了 1404 例连续诊断为分支胰管 IPMN 的患者（52%为女性；平均年龄 67.5 岁）。采用竞争风险分析，我们估计了胰腺癌的累积发生率，包括总体发生率和按癌种分类的发生率。我们使用竞争风险比例风险模型来估计癌发生率的亚分布风险比（SHR）。为了区分 IPMN 相关性癌和同时性癌，我们从可用的 IPMN 和癌配对样本中收集基因组 DNA，并通过聚合酶链反应和焦磷酸测序检测 GNAS 和 KRAS 突变。
在 9231 人年的随访期间，我们共发现 68 例胰腺癌患者（38 例为 IPMN 相关性癌，30 例为同时性 PDAC）；5、10 和 15 年时的总体发生率分别为 3.3%、6.6%和 15.0%。在 804 例随访时间超过 5 年的患者中，从初始诊断时起，10 年和 15 年时的总体胰腺癌累积发生率分别为 3.5%和 12.0%。IPMN 的大小和主胰管的直径与 IPMN 相关性癌的发生率相关（IPMN 大小增加 10mm 的 SHR 为 1.85；95%置信区间 1.38-2.48；主胰管直径增加 1mm 的 SHR 为 1.56；95%置信区间 1.33-1.83），但与同时性 PDAC 的发生率无关。
在一项针对分支胰管 IPMN 患者的大型长期研究中，我们发现 5 年恶性肿瘤发生率为 3.3%，在 IPMN 诊断后 15 年达到 15.0%。我们观察到 IPMN 相关性癌和同时性癌的危险因素谱存在异质性。
