胰腺癌术后肿瘤初始复发部位对预后的影响

The impact of initial recurrence site on the prognosis for pancreatic cancer after radical operation

目的探讨胰腺癌根治性手术后初始复发部位对患者预后的影响。方法回顾性分析2015年1月至2021年6月间宁波大学附属李惠利医院172例行胰腺癌根治性手术切除且病理确诊为胰腺导管腺癌患者的临床资料,根据术后肿瘤初始复发或转移部位分为无复发、局部复发(残余胰腺或肠系膜血管、胰肠吻合口周围组织等处复发)、肝转移、腹腔或后腹膜转移、多部位复发及其他部位转移等。采用COX风险比率模型分析影响患者预后的危险因素,采用Kaplan-Meier法计算患者总生存期和无瘤生存期,绘制生存曲线,采用log-rank法比较不同复发部位及复发后不同治疗方案患者的生存期差异。结果172例患者术后12例局部复发,69例肝转移,25例腹腔或后腹膜转移,17例多部位复发,5例其他部位转移,44例未复发;中位随访时间15.5个月(3~69个月);患者中位总生存期为19个月(95%CI 16.273~21.727);术后1、3、5年累积生存率分别为71.0%、27.8%、20.2%。单因素分析结果显示CA125水平、肿瘤大小、淋巴结转移、脉管侵犯、肿瘤分化程度、辅助化疗、初始复发转移部位与患者总生存期显著相关(P值均<0.05);多因素分析结果显示,CA125≥30 IU/ml(OR=2.669,P=0.001)、脉管侵犯(OR=1.736,P=0.028)、肿瘤低分化(OR=1.604,P=0.027)、辅助化疗(OR=0.439,P<0.001)、初始复发转移部位(P值均<0.05)是影响患者总生存期的独立危险因素。172例患者的中位无瘤生存期为9个月(95%CI 7.075~10.925)。单因素分析结果显示,CA125水平、肿瘤大小、淋巴结转移、脉管侵犯与患者无瘤生存期显著相关(P值均<0.05);多因素分析结果显示,CA125水平(OR=1.640,P=0.026)、肿瘤大小(OR=1.774,P=0.011)、脉管侵犯(OR=1.563,P=0.034)是影响患者无瘤生存期的独立危险因素。胰腺癌术后,局部复发、其他部位转移、腹腔或后腹膜转移、多部位复发、肝转移患者的中位生存期分别为28、22、21、15、14个月,其中术后局部复发患者生存期最长,显著长于多部位复发(P=0.035)和肝转移(P=0.007)患者,腹腔或后腹膜转移患者生存期也显著长于肝转移患者(P=0.005),差异均有统计学意义。128例复发患者中26例患者未予治疗,其中位生存期为10个月(95%CI 6.877~13.123);68例采用单纯化疗方案,其中位生存期为15个月(95%CI 13.013~16.987);34例采用化疗结合再次手术、放疗等综合治疗,其中位生存期为19个月(95%CI 15.100~22.900),显著高于未治疗和单纯化疗患者,3组间差异有统计学意义(P<0.001)。结论胰腺癌根治性手术后肿瘤初始复发部位是影响患者术后生存的独立危险因素。相比于局部复发和腹腔或后腹膜转移,多部位复发和肝转移患者的预后较差。复发后综合治疗可显著延长患者总生存期。

Objective To investigate the impact of initial recurrence site on the prognosis of patients with pancreatic cancer after radical operation.Methods Clinical data of 172 patients who underwent radical resection of pancreatic cancer and were pathologically confirmed as pancreatic ductal adenocarcinoma in Ningbo University Affiliated Lihuili Hospital from January 2015 to June 2021 were analyzed retrospectively.According to the classification of the initial recurrence or metastasis after operation:no recurrence,local recurrence(residual pancreas,mesenteric vein,pancreaticoenterostomy surrounding tissue),liver metastasis,abdominal or retroperitoneum metastasis,multiple site recurrence and other pattern recurrence.The effect on prognosis was analyzed by COX risk ratio model,the overall survival and recurrence-free survival were calculated by Kaplan-Meier,and the survival curve was drawn.Log-rank test was used to compare the survival rate of different recurrence sites and different treatments after recurrence.Results 12 patients had local recurrence,69 had liver metastasis,25 had abdominal or retroperitoneal metastasis,17 had multiple site recurrence,and 5 had other site recurrence and 44 had no recurrence.The median follow-up time was 15.5 months(3-69 months).The median overall survival was 19 months(95%CI 16.273-21.727).The 1-,3-and 5-year postoperative cumulative survival rate was 71.0%,27.8%and 20.2%,respectively.Univariate analysis showed that CA125,tumor size,lymph node metastasis,microvascular invasion,tumor differentiation degree,adjuvant chemotherapy,initial recurrence site were significantly correlated with overall survival(All P value<0.05).Multivariate analysis showed that CA125≥30 IU/ml(OR=2.669,P=0.001),microvascular invasion(OR=1.736,P=0.028),poor tumor differentiation(OR=1.604,P=0.027),adjuvant chemotherapy(OR=0.439,P<0.001),initial recurrence site(All P value<0.05)were the independent risk factors for overall survival.The median recurrence-free survival of 172 patients was 9 months(95%CI 7.075-10.925).Univariate analysis showed that CA125,tumor size,lymph node metastasis and microvascular invasion were significantly correlated with recurrence-free survival(All P value<0.05).Multivariate analysis showed that CA125(OR=1.640,P=0.026),tumor size(OR=1.774,P=0.011)and microvascular invasion(OR=1.563,P=0.034)were the independent risk factors for recurrence-free survival.After surgery,the median survival time of patients with local recurrence,other pattern recurrence,abdominal or retroperitoneal metastasis,multi-site recurrence and liver metastasis was 28,22,21,15 and 14 months,respectively.Among them,the overall survival of patients with postoperative local recurrence was longest,which was significantly longer than that of patients with multi-site recurrence(P=0.035)and liver metastasis(P=0.007);the survival of patients with abdominal or retroperitoneal metastasis was also longer than that with liver metastasis(P=0.005);and all the differences were statistically significant.In 128 patients with recurrence,the median overall survival of 26 patients without adjuvant therapy was 10 months(95%CI 6.877-13.123);the median overall survival of 68 patients with adjuvant chemotherapy was 15 months(95%CI 13.013-16.987);the median overall survival of 34 patients with comprehensive treatment of surgery and radiotherapy was 19 months(95%CI 15.100-22.900),which was significantly higher than the other two groups,and there were significant statistical differences among the three groups(P<0.001).Conclusions The initial recurrence site of pancreatic cancer after radical operation is an independent risk factor for overall survival.Compared with local recurrence and abdominal or retroperitoneal metastasis,patients with multi-site recurrence and liver metastasis have a poor prognosis.Comprehensive treatment after recurrence can significantly prolong the overall survival.