Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study

Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study
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DOI:
10.1016/j.gie.2008.07.033
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发表时间:
2009-05-01
影响因子:
7.7
通讯作者:
McGrath, Kevin M.
McGrath, Kevin M.
中科院分区:
医学1区
文献类型:
--
作者:
Khalid, Asif;Zahid, Maliha;McGrath, Kevin M.

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背景:胰腺囊肿液 DNA 分析在评估囊肿中的作用尚不清楚。目的:我们的目的是评估胰腺囊肿液详细 DNA 分析在诊断粘液性和恶性囊肿中的效用。设计:前瞻性、多中心研究。患者:接受 EUS 评估的胰腺囊肿患者。干预:EUS 引导下胰腺囊肿抽吸细胞学评估、癌胚抗原 (CEA) 水平测定和详细 DNA 分析;主要结果测量:囊液分析与手术病理或恶性细胞学检查相比较结果:研究队列由 113 名患者组成,其中 40 例恶性、48 例癌前和 25 例良性囊肿。囊液 k-ras 突变有助于粘液性囊肿的诊断(比值比 20.9,特异性) 96%),而接受者-操作者特征曲线分析表明等位基因丢失幅度(曲线下面积 [AUC] 0.79;最佳值 > 65%)和 CEA(AUC 0.74;最佳值 > 148 ng/ml)的最佳截止点。检测恶性囊肿的 DNA 分析成分包括等位基因丢失幅度超过 82% (AUC 0.9) 和高 DNA 量(光密度比 > 10,AUC 0.79)。高幅度 k-ras 突变随后等位基因丢失的标准显示出对恶性肿瘤的最大特异性 (96%)。所有细胞学评估阴性(10/40)的恶性囊肿均可通过DNA分析诊断为恶性。局限性:统一随访,选择偏倚。结论:胰腺囊肿液DNA量升高,高幅度突变,中特异突变获取序列是恶性的指标。 k-ras 突变的存在也表明存在粘液性囊肿。当囊肿细胞学检查恶性肿瘤呈阴性时,应考虑进行 DNA 分析。 (胃肠测试 Endosc 2009;69:1095-102。)
Background: The role of pancreatic cyst fluid DNA analysis in evaluating cysts remains unclear.Objective: Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cyst.Design: Prospective, multicenter study.Patients: Patients with pancreatic cysts presenting for EUS evaluation.Intervention: EUS-guided pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA) level determination, and a detailed DNA analysis; incorporating DNA quantification, k-ras mutation and multiple allelic has analysis, mutational amplitude, and sequence determination.Main Outcome Measurements: Cyst fluid analysis compared with surgical pathologic or malignant cytologic examinationResults: The study cohort consisted of 113 patients with 40 malignant, 48 premalignant, and 25 benign cyst Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver-operator characteristic curve analysis indicated optimal cutoff points For allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and CEA (AUC 0.74; optimal value > 148 ng/ml). Components of DNA analysis detecting malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA amount (optical density ratio > 10, AUC 0.79). The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy. All malignant cysts with negative cytology evaluation (10/40) could be diagnosed as malignant by using DNA analysis.Limitations: United follow-up, selection bias.Conclusions: Elevated amounts of pancreatic cyst fluid DNA hi,high-amplitude mutations, Mid specific mutation acquistion sequences we indicators of malignancy. The presence of a k-ras mutation is also indicative of a mucinous cyst. DNA analysis should be considered when cyst cytologic examination is negative for malignancy. (Gastrointest Endosc 2009;69:1095-102.)