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使用超灵敏数字聚合酶链反应检测切除的胰腺导管腺癌切缘KRAS突变负荷预测复发情况

Prediction of Recurrence With KRAS Mutational Burden Using Ultrasensitive Digital Polymerase Chain Reaction of Radial Resection Margin of Resected Pancreatic Ductal Adenocarcinoma.

作者信息

Kim Sung Joo, Kim Mi-Ju, Han Ji-Soo, Sung You-Na, An Soyeon, Lee Jae Hoon, Song Ki Byung, Hwang Dae Wook, Lee Sang Soo, Cho HyungJun, Kim Song Cheol, Eshleman James R, Hong Seung-Mo

机构信息

Asan Institute for Life Sciences, Asan Medical Center.

Department of Statistics, Korea University, Seoul.

出版信息

Pancreas. 2019 Mar;48(3):400-411. doi: 10.1097/MPA.0000000000001255.

Abstract

OBJECTIVE

Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated.

METHODS

KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation.

RESULTS

KRAS mutation was detected in 76 patients (94%), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19% or greater was observed in 18 patients (22%). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses.

CONCLUSIONS

KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.

摘要

目的

尽管完整手术切除是胰腺癌唯一的治愈方法,但保留幽门的胰十二指肠切除术标本的径向切缘可能评估不足。

方法

采用液滴数字聚合酶链反应对81例患者径向切缘采集的细胞进行KRAS突变评估,并将结果与传统病理切缘(pRM)评估结果进行比较。

结果

76例患者(94%)检测到KRAS突变,18例患者(22%)观察到KRAS突变率≥4.19%定义的分子切缘(mRM)阳性。在整个组以及未接受化疗或放疗的亚组中,mRM阳性患者的无复发生存期(RFS)显著低于mRM阴性患者(全部,P<0.001)。单因素(P=0.002)和多因素(P=0.03)分析显示,联合评估pRMs-mRMs时,联合pRM-mRM阳性(pRM或mRM阳性)患者的RFS显著低于联合切缘阴性(pRM和mRM均阴性)患者。

结论

对于接受保留幽门胰十二指肠切除术的胰腺癌患者,采用超灵敏液滴数字聚合酶链反应对径向切缘进行KRAS突变分析,单独使用或与传统pRM评估联合使用,可为RFS提供更准确的信息,尤其是在未接受化疗或放疗的患者中。

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