Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.
Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
JAMA Surg. 2021 Jul 1;156(7):654-661. doi: 10.1001/jamasurg.2021.1802.
The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information.
To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations.
DESIGN, SETTING, AND PARTICIPANTS: The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months).
Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination.
A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001).
These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.
胰腺内导管乳头状黏液性肿瘤（IPMNs）向恶性疾病的进展仍然知之甚少。观察性和手术系列未能提供全面的信息。
通过将病理特征与术前重复观察的数据相结合，确定与恶性肿瘤发展相关的动态变量。
设计、设置和参与者：交叉观察性多中心研究纳入了 2000 年 1 月 1 日至 2019 年 12 月 31 日期间参加监测计划的分支胰管 IPMNs（BD IPMNs）的回顾性队列患者。患者来自 5 个转诊中心：意大利维罗纳的胰腺研究所、韩国首尔国立大学医院、新加坡综合医院、马里兰州巴尔的摩的约翰霍普金斯医学院和德克萨斯大学 MD 安德森癌症中心。患者接受了至少 12 个月的术前监测（中位数，37 [四分位距（IQR），20-68] 个月）。
探讨了与恶性疾病相关的动态变量，以估计最终病理检查中存在高级别异型增生（HGD）和浸润性癌的情况。
共纳入 292 名患者进行分析（137 名女性[46.9%]和 155 名男性[53.1%]；中位年龄为 64 [IQR，56-71] 岁）。在监测期间，27 名患者（9.2%）在 5 年后出现了令人担忧的特征，276 名患者中有 46 名（16.7%）出现了高危标志物（HRS）。在最终的病理评估中，107 名患者（36.6%）有 HGD 或浸润性癌，16 名患者（5.5%）有同时伴有胰腺导管腺癌的 IPMNs。在没有令人担忧特征的患者和从先前令人担忧特征发展为 HRS 的患者中，HGD 和浸润性癌的病理评估率有显著差异（9 [27.3%] 与 13 [61.9%]；P<0.001）。在监测期间出现另一个令人担忧的特征（优势比[OR]，3.24 [95%CI，1.38-7.60]；P=0.007）或从基线令人担忧特征发展为 HRS（OR，2.87 [95%CI，1.01-8.17]；P=0.048）与最终病理评估中的 HGD 相关。在 HRS 中，低危囊肿出现黄疸与浸润性癌独立相关（OR，16.04 [95%CI，2.94-87.40]；P=0.001）。
这些发现表明，在接受监测的 BD IPMNs 中，存在稳定的令人担忧的特征时，恶性疾病的风险最低。出现额外的令人担忧的特征或 HRS 与 HGD 有关，而出现黄疸与浸润性癌有关。
