胰腺星状细胞活跃度在胰十二指肠切除术后胰瘘中的预测价值

Predictive value of pancreatic stellate cell activity for postoperative pancreatic fistula after pancreaticoduodenectomy

背景与目的:胰腺质地是胰十二指肠切除(PD)术后胰瘘(POPF)发生的重要影响因素,但胰腺质地的判断缺乏客观评价标准。研究发现,胰腺星状细胞(PSC)的活化与胰腺的纤维化的发生密切相关,因而其活性可能影响胰腺质地。因此,本研究探讨PSC活跃度预测PD术后临床相关性胰瘘(CR-POPF)的可行性与有效性。方法:前瞻性收集2017年12月—2019年9月中南大学湘雅医院连续收治的101例行PD术患者的切缘处胰腺病理标本。通过免疫组化染色的α-平滑肌肌动蛋白(α-SMA)检测PSC的活跃度,并进行分级。分析PSC活跃度与胰腺质地及CR-POPF发生的关系,以及其他相关临床因素与CR-POPF发生的关系,用ROC曲线评价PSC活跃度预测CR-POPF的效能。结果:101例患者中,41例(40.6%)出现CR-POPF。分析结果显示,随着PSC活跃度等级的升高,CR-POPF发生率呈明显递减趋势,不同的胰腺质地之间,PSC等级的分布具有统计学差异(均P<0.001)。相关性分析结果显示,PSC活跃度与胰腺质地的硬度之间存在明显正相关性(r=0.456,P<0.001),而与CR-POPF发生率之间则存在明显负相关性(r=-0.539,P<0.001)。单因素分析结果显示,胰腺质地、胰腺病理、PSC活跃度分级、术前体质量指数、胰管直径、术前总胆红素、第1天腹腔引流液淀粉酶与CR-POPF的发生密切相关(均P<0.05);多元回归分析结果显示,PSC活跃度分级(OR=0.24,95%CI=0.10~0.56,P<0.001)和术前总胆红素(OR=1.01,95%CI=1.00~1.01,P=0.008)是CR-POPF的独立危险因素。ROC曲线分析显示,PSC活跃度预测CR-POPF的AUC为0.795(95%CI=0.708~0.881),敏感度和特异度分别为63.3%和87.8%。结论:PSC活跃度等级能较客观、准确地反映胰腺的质地情况,是预测PD术后CR-POPF的有效指标,具有一定的临床应用价值。

Background and Aims:The texture of the pancreas is an important factor for the occurrence of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD).However,there are no objective evaluation criteria for estimating the hardness of the pancreatic texture.Studies have demonstrated that the activation of the pancreatic stellate cells (PSCs) is closely associated with the pancreatic fibrosis,and therefore,their activity may probably influence the texture of the pancreas.This study was designated to investigated the feasibility and effectiveness of using the degree of PSC activity for predicting the clinically relevant postoperative pancreatic fistula (CR-POPF) after PD.Methods:The surgical margin samples from 101 consecutive patients who underwent PD in the Department of Pancreatic Surgery,Xiangya Hospital,Central South University from December 2017 to September 2019 were prospectively collected.The degree of PSC activity was determined and graded by immunohistochemical staining of α-smooth muscle actin (α-SMA) protein.The relations of PSC activity with CR-POPF and the pancreatic texture,as well as the relations of other relevant clinicopathologic factors with CR-POPF were analyzed.The efficiency of PSC activity in predicting CR-POPF was determined by ROC analysis.Results:In the 101 patients,CR-POPF occurred in 41 cases (40.6%).Results of analysis showed that the incidence of CR-POPF was decreased progressively with the increase of the grade of PSC activity,and the distributions of PSC activity grades were significantly different among different pancreatic textures (both P<0.001).Results of correlation analysis showed that the degree of PSC activity was positively correlated with the hardness of pancreatic texture (r=0.456,P<0.001),while was negatively correlated with the incidence of CR-POPF (r=–0.539,P<0.001).Results of univariate analysis showed that pancreatic texture,tumor pathology,PSC activity grade,preoperative body mass index,pancreatic duct diameter,preoperative total bilirubin,drainage fluid amylase on postoperative day 1 were significantly associated with the occurrence of CR-POPF (all P<0.05),and the results of multivariate Logistic regression analysis showed that the PSC activity (OR=0.24,95% CI=0.10–0.56,P<0.001) and preoperative total bilirubin (OR=1.01,95% CI=1.00–1.01,P=0.008) were the independent risk factors for CR-POPF.Results of ROC analysis showed that the AUC of the degree of PSC activity for predicting CR-POPF was 0.795 (95% CI=0.708–0.881),with a sensitivity of 63.3% and a specificity of 87.8%.Conclusion:The degree of PSC activity can objectively and accurately reflect the hardness of the pancreatic texture.It is an effective index for predicting the CR-POPF following PD,and has certain clinical application value.