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胆汁中血管内皮生长因子水平可区分胰腺癌与其他胆道狭窄病因:一项初步研究。

Vascular endothelial growth factor levels in bile distinguishes pancreatic cancer from other etiologies of biliary stricture: a pilot study.

机构信息

Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk A30, The Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, 44195, USA,

出版信息

Dig Dis Sci. 2013 Oct;58(10):2986-92. doi: 10.1007/s10620-013-2764-0. Epub 2013 Jul 5.

Abstract

BACKGROUND

Determining the benign or malignant nature of biliary strictures can be challenging. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis.

OBJECTIVE

The purpose of this study was to investigate whether VEGF levels in bile aspirated during endoscopic retrograde cholangiography (ERCP) can distinguish pancreatic cancer from other causes of biliary stricture.

METHODS

Bile was directly aspirated in 53 consecutive patients from March 2012 to October 2012 during ERCP from the common bile duct including 15 with pancreatic cancer, 18 with primary sclerosing cholangitis (PSC), nine with cholangiocarcinoma (CCA), and 11 with benign biliary conditions (sphincter of Oddi and choledocholihiasis). Levels of VEGF in bile were measured. The diagnostic performance was then validated in a second, independent validation cohort of 18 patients (pancreatic cancer n = 10, benign n = 8).

RESULTS

A total of 53 consecutive patients were recruited. The median bile VEGF levels were significantly elevated in patients with pancreatic cancer (1.9 ng/ml (interquartile range [IQR] 0.7, 2.2) compared to those with benign biliary conditions (0.3 ng/ml [IQR 0.2, 0.6]; p < 0.001), PSC (0.7 ng/ml [IQR 0.5, 0.9]; p = 0.02) or CCA (0.4 ng/ml [IQR 0.1, 0.5]; p < 0.001). A VEGF cut-off value of 0.5 ng/ml distinguished pancreatic cancer from CCA with a sensitivity and specificity of 93.3 and 88.9 %, respectively, and area under curve (AUC) of 0.93, and from benign conditions with a sensitivity and specificity of 93.3 and 72.7 %, respectively, with AUC of 0.89. The diagnostic accuracy of biliary VEGF was confirmed in the second independent validation cohort.

CONCLUSIONS

This study suggests that measurement of biliary VEGF-1 levels distinguishes patients with pancreatic cancer from other etiologies of biliary stricture. This may be particularly relevant in approaching patients with indeterminate biliary stricture.

摘要

背景

确定胆管狭窄的良恶性性质具有挑战性。血管内皮生长因子(VEGF)在肿瘤血管生成中发挥重要作用。

目的

本研究旨在探讨经内镜逆行胰胆管造影(ERCP)时抽吸的胆汁中 VEGF 水平是否可用于区分胰腺癌与其他原因引起的胆管狭窄。

方法

2012 年 3 月至 2012 年 10 月,连续 53 例在 ERCP 时从胆总管直接抽吸胆汁的患者,包括 15 例胰腺癌患者、18 例原发性硬化性胆管炎(PSC)患者、9 例胆管癌(CCA)患者和 11 例良性胆道疾病(Oddi 括约肌和胆石症)患者。测量胆汁中 VEGF 的水平。然后在第二个独立验证队列中对 18 例患者(胰腺癌 n = 10,良性 n = 8)进行验证。

结果

共纳入 53 例连续患者。胰腺癌患者的胆汁 VEGF 水平中位数明显升高(1.9ng/ml[四分位距(IQR)0.7,2.2]与良性胆道疾病患者(0.3ng/ml[IQR 0.2,0.6];p <0.001)、PSC 患者(0.7ng/ml[IQR 0.5,0.9];p = 0.02)或 CCA 患者(0.4ng/ml[IQR 0.1,0.5];p <0.001)。VEGF 截断值为 0.5ng/ml 时,可将胰腺癌与 CCA 区分开,其灵敏度和特异性分别为 93.3%和 88.9%,曲线下面积(AUC)为 0.93,与良性疾病的灵敏度和特异性分别为 93.3%和 72.7%,AUC 为 0.89。在第二个独立验证队列中,验证了胆汁 VEGF 的诊断准确性。

结论

本研究表明,胆汁 VEGF-1 水平的测量可将胰腺癌患者与其他胆道狭窄病因区分开来。这在处理不确定的胆道狭窄患者时可能特别相关。

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