肝硬化血清标志物对腹腔镜脾切除联合贲门周围血管离断术后发生食管胃底曲张静脉再出血预测价值的前瞻性研究

The value of liver fibrosis serum markers in predicting esophagogastric variceal re-bleeding after laparoscopic splenectomy and azygoportal disconnection: a prospective study

  • 摘要:
    目的 探讨肝硬化血清标志物对腹腔镜脾切除联合贲门周围血管离断术后发生食管胃底曲张静脉再出血(EGVR)的预测价值。
    方法 采用前瞻性研究方法。选取2014年9月至2017年1月扬州大学临床医学院收治的155例肝硬化门静脉高压症行腹腔镜脾切除联合贲门周围血管离断术后发生EGVR患者的临床资料。观察指标:(1)入组患者情况。(2)术后发生EGVR的危险因素分析。(3)术后发生EGVR的预测情况。(4)随访情况。采用电话、门诊和住院方式进行随访。术后每3个月随访1次。了解患者术后发生EGVR及死亡情况。随访时间截至2018年1月。正态分布的计量资料以x±s表示,组间比较采用t检验;偏态分布的计量资料以M(范围)表示,组间比较采用非参数检验。计数资料以绝对数表示,组间比较采用χ²检验或Fisher确切概率法。多因素分析采用Logistic回归模型。采用受试者工作特征曲线下面积(AUC)评估诊断效能,约登指数确定最佳截断值。
    结果 (1)入组患者情况。筛选出符合条件的患者155例;男106例,女49例;年龄为(53±11)岁。155例患者中,术后1年内发生EGVR 21例,未发生EGVR 134例。发生EGVR和未发生EGVR患者层粘连蛋白、Ⅳ型胶原分别为100.3(16.1~712.2)μg/L、68.4(35.0~198.8)μg/L和35.5(2.0~521.2)μg/L、43.5(4.3~150.4)μg/L,两者比较,差异均有统计学意义(Z=-4.55,-4.52,P<0.05)。(2)术后发生EGVR的危险因素分析。根据约登指数,层粘连蛋白最佳截断值为64 μg/L,Ⅳ型胶原最佳截断值为65 μg/L。多因素分析结果显示:层粘连蛋白≥64 μg/L,Ⅳ型胶原≥65 μg/L是患者术后发生EGVR的独立危险因素(优势比=9.69,8.16,95可信区间为3.05~30.82,2.65~25.15,P<0.05)。(3)术后发生EGVR的预测情况。受试者工作特征曲线分析结果显示:层粘连蛋白和Ⅳ型胶原预测术后发生EGVR的AUC为0.79(95%可信区间为0.66~0.92),灵敏度为0.62,特异度为0.96。(4)随访情况。155例患者均获得随访,随访时间为12(1~12)个月。随访期间,13.55%(21/155)的患者术后发生EGVR并发症,其中3例死于EGVR。21例术后发生EGVR的患者中,6例发生于术后1个月内,其中2例死亡;5例发生于术后1~3个月;6例发生于>术后3个月且<术后6个月,4例发生于术后6~12个月,其中1例术后12个月死亡。
    结论 层粘连蛋白和Ⅳ型胶原可良好预测腹腔镜脾切除联合贲门周围血管离断术后发生EGVR。

     

    Abstract:
    Objective To investigate the value of liver fibrosis serum markers in predicting esophagogastric variceal re-bleeding (EGVR) after laparoscopic splenectomy and azygoportal discon-nection (LSD).
    Methods The prospective study was conducted. The clinical data of 155 cirrhotic portal hypertension patients with EGVR after LSD in the Clinical Medical College of Yangzhou University from September 2014 to January 2017 were selected. Observation indicators: (1) grouping situations of the enrolled patients; (2) risk factors analysis for postoperative EGVR; (3) prediction of postoperative EGVR; (4) follow-up. Follow-up was conducted using telephone interview, outpatient examination and hospitalization. Patients were followed up once every 3 months after operation to detect occurrence of EGVR and survival of patient up to January 2018. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data wite skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups were conducted using the chi-square test or Fisher exact probability. Logistic regression model was used for multivariate analysis. The area under curve (AUC) of receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficiency. The Youden index was used to determine the optimal cut-off point.
    Results (1) Grouping situations of the enrolled patients. A total of 155 patients were selected for eligibility. There were 106 males and 49 females, aged (53±11)years. Of the 155 patients, there were 21 cases with EGVR in the postoperative 1 year and 134 cases without EGVR in the postoperative 1 year. The protein expression of laminin and collagen Ⅳ were 100.3(range, 16.1‒712.2)µg/L and 68.4(range, 35.0‒198.8)µg/L in patients with EGVR, vs 35.5(range, 2.0‒521.2)µg/L and 43.5(range, 4.3‒150.4)µg/L in patients without EGVR, showing significant differences between them (Z=‒4.55, ‒4.52, P<0.05). (2) Risk factors analysis for postoperative EGVR. According to the Youden index, the optimal cut-off point of protein expression of laminin and collagen Ⅳ were 64.0 µg/L and 65.0 µg/L, respec-tively. Results of multivariate analysis showed that the protein expression of laminin ≥64.0 µg/L and the protein expression of collagen Ⅳ ≥65.0 µg/L were independent risk factors for postoperative EGVR (odds ratio=9.69, 8.16, 95 confidence intervals as 3.05‒30.82, 2.65‒25.15, P<0.05). (3) Prediction of postoperative EGVR. Results of ROC curve showed that the AUC of laminin and collagen Ⅳ in predicting postoperative EGVR was 0.79 (95% confidence interval as 0.66‒0.92), with sensi-tivity as 0.62 and specificity as 0.96. (4) Follow-up. All the 155 patients were followed up for 12(range, 1‒12)months. During the follow-up, there were 21 of the 155 patients (13.55%) with post-operative EGVR, including 3 cases died of EGVR. Of the 21 patients with postoperative EGVR, there were 6 cases with postoperative EGVR during the first month after operation including 2 cases died, 5 cases with postoperative EGVR at postoperative 1‒3 month, 6 cases with postoperative EGVR more than 3 month and less than 6 month after operation and 4 cases with postoperative EGVR at postoperative 6‒12 months including 1 case died at postoperative 12 month.
    Conclusions Laminin and collagen Ⅳ show satisfactory ability to predict EGVR after LSD.

     

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