Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection
Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection
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DOI：
10.1038/s41379-019-0405-7
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发表时间：
2020-05-01
期刊：
影响因子：
7.5
通讯作者：
Katanuma, Akio
中科院分区：
文献类型：
--
作者：
Nagai, Kazumasa;Mizukami, Yusuke;Katanuma, Akio
切除后残胰导管内乳头状黏液性肿瘤的异时发展是一个重大的临床负担。我们的目的是描述异时性肿瘤患者的临床病理学和分子特征，以确定预测因素和可能的传播途径。回顾性分析了74例接受导管内乳头状粘液性肿瘤切除术的患者，这些患者没有浸润性间室或相关癌。在异时性肿瘤发展的患者中，对原发性和异时性肿瘤进行了与胰腺肿瘤发生相关的18个基因的靶向测序和4种蛋白质（p53，SMAD 4，p16和β-连环蛋白）的免疫组化检测。在手术切缘和除原发肿瘤外的明显正常组织中检查显微镜下肿瘤性病变的分布。在52个月的中位随访期内，9例患者（12%）在残余胰腺中发生异时性肿瘤。原发性肿瘤位于胰腺体/尾（比值比，15; 95%置信区间，1.6-131）和胰胆型（比值比，6.1; 95%置信区间，1.1-35.7）被确定为随后异时性肿瘤发展的重要风险因素。9例患者中有8例在原发性和异时性肿瘤之间存在分子畸变，这表明从原发性肿瘤迁移到胰管是异时性肿瘤发展的原因。我们的数据表明，这些切除后异时性肿瘤的发展跳跃扩散的原发肿瘤，可能通过胰管。有必要制定更好地预测和预防这种形式的肿瘤进展的策略。
Metachronous development of intraductal papillary mucinous neoplasms in the remnant pancreas following resection is a significant clinical burden. Our aim was to characterize the clinicopathological and molecular features of the patients with metachronous tumor development to identify predictive factors and the possible route(s) of dissemination. Seventy-four patients who underwent resection of intraductal papillary mucinous neoplasms with no invasive compartment or associated carcinoma were retrospectively analyzed. In patients with metachronous tumor development, targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical detection of four proteins (p53, SMAD4, p16, and beta-catenin) were performed on both primary and metachronous tumors. The distributions of microscopic neoplastic lesions were examined at surgical margins and in apparently normal tissue apart from the primary tumor. During the median follow-up period of 52 months, 9 patients (12%) developed metachronous tumors in the remnant pancreas. Primary tumors located in the body/tail of the pancreas (odds ratio, 15; 95% confidence interval, 1.6-131) and of the pancreatobiliary type (odds ratio, 6.1; 95% confidence interval, 1.1-35.7) were identified as significant risk factors for subsequent metachronous tumor development. Eight of the nine patients shared molecular aberrations between their primary and metachronous tumors, suggesting migrations from the primary tumor to the pancreatic duct as the cause of metachronous tumor development. Our data suggest that these post-resection metachronous tumors develop by skip dissemination of the primary tumor, potentially via the pancreatic duct. The development of strategies to better predict and prevent this form of tumor progression is necessary.