1 Institute for Technology Assessment, Massachusetts General Hospital, 101 Merrimac St, Ste 1010, Boston, MA 02114.
2 Department of Radiology, Massachusetts General Hospital, Boston, MA.
AJR Am J Roentgenol. 2019 Mar;212(3):596-601. doi: 10.2214/AJR.18.20180. Epub 2019 Jan 8.
The objective of our study was to test for the possibility that published malignancy risks for side-branch intraductal papillary mucinous neoplasms (IPMNs) are overestimates, likely due to verification bias.
We tested for possible verification bias using simulation modeling techniques. First, in age-defined hypothetical cohorts of 10 million persons, we projected the frequency of pancreatic ductal adenocarcinoma (PDAC) arising from side-branch IPMNs over 5 years using published estimates of their prevalence (4.4%) and rate of malignant transformation (1.9%). Second, we projected the total number of PDAC cases in corresponding cohorts over the same time horizon using national cancer registry data. For each cohort, we determined whether the percentage of all PDAC cases that arose from side-branch IPMNs (i.e., side-branch IPMN-associated PDAC cases) was clinically plausible using an upper limit of 10% to define plausibility, as estimated from the literature. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis.
Across all cohorts, percentages of side-branch IPMN-associated PDACs greatly exceeded 10%. In the base case (mean age = 55.7 years), 80% of PDAC cases arose from side-branch IPMNs (7877/9786). In the oldest cohort evaluated (mean age = 75 years), this estimate was 76% (14,227/18,714). In a secondary analysis, we found that if an upper limit threshold of 10% for side-branch IPMN-associated PDAC was imposed, the model-predicted rate of malignancy for side-branch IPMNs would be less than 0.24% over a 5-year time horizon, substantially lower than most literature-based estimates.
Our results suggest that reported malignancy risks associated with side-branch IPMNs are likely to be overestimates and imply the presence of verification bias.
我们的研究旨在检验发表的侧支分支型胰管内乳头状黏液性肿瘤（IPMN）恶性风险是否过高，这可能是由于验证偏倚所致。
我们使用模拟建模技术检验了可能存在的验证偏倚。首先，在年龄定义的 1000 万假设人群队列中，我们使用发表的侧支 IPMN 患病率（4.4%）和恶性转化率（1.9%）估计值，预测 5 年内源自侧支 IPMN 的胰腺导管腺癌（PDAC）的发生率。其次，我们使用国家癌症登记数据，预测同一时间范围内相应队列中 PDAC 的总病例数。对于每个队列，我们使用文献中估计的 10%上限来确定源自侧支 IPMN 的所有 PDAC 病例（即侧支 IPMN 相关 PDAC 病例）的百分比是否具有临床意义。在敏感性分析中评估了模型假设和参数不确定性。
在所有队列中，侧支 IPMN 相关 PDAC 的比例均大大超过 10%。在基本情况下（平均年龄=55.7 岁），80%的 PDAC 病例源自侧支 IPMN（7877/9786）。在评估的最年长队列中（平均年龄=75 岁），这一估计值为 76%（14227/18714）。在二次分析中，我们发现如果将侧支 IPMN 相关 PDAC 的上限阈值设定为 10%，则模型预测的侧支 IPMN 恶性率在 5 年内将低于 0.24%，远低于大多数基于文献的估计值。
我们的结果表明，与侧支 IPMN 相关的报道恶性风险可能过高，这表明存在验证偏倚。
