侵袭性胰腺导管内乳头状黏液性肿瘤与胰腺导管腺癌的生存差异分析

Prognostic differences between intraductal papillary mucinous neoplasm of the pancreas and pancreatic ductal adenocarcinoma

目的分析侵袭性胰腺导管内乳头状黏液性肿瘤(IPMN)与胰腺导管腺癌(PDAC)的生存差异。方法研究对象为2012年1月—2022年6月在复旦大学附属中山医院普外科行手术治疗且临床资料完整的侵袭性IPMN患者91例和PDAC患者893例,术后病理明确诊断为侵袭性IPMN或PDAC,PDAC患者均行化学治疗(简称化疗)。收集所有患者的基线特征(性别、年龄、首发症状或疾病、糖尿病史、ASA分级、术前CA19-9水平),手术情况(手术时长、术中失血量、手术方式、动脉和静脉侵犯),术后并发症(胰漏、胃瘫、肺栓塞、出血),再手术率,术后拔除引流管、胃管的时间,住院时长,术后病理特征(肿瘤直径、TNM分期、周围脂肪浸润、脉管浸润),术后肿瘤复发或转移,以及辅助治疗情况。应用Rstudio 4.22的survminer包绘制生存曲线,两组生存曲线分析采用Kaplan-Meier法比较,采用Log-Rank检验。采用Cox风险回归模型进行多因素logistic回归分析侵袭性IPMN患者中位生存时间的影响因素。结果两组间年龄、各首发症状或疾病患者占比、术前CA19-9水平比较,差异均有统计学意义(P<0.05或0.01)。两组间患者各手术方式及肿瘤有无静脉侵犯患者占比比较,差异均有统计学意义(P值均<0.01);两组间手术时长、术中失血量、肿瘤有无动脉侵犯患者占比比较,差异均无统计学意义(P值均>0.05)。两组间术后各级胰瘘、胃瘫发生率比较,差异均有统计学意义(P<0.01或0.05);两组间术后肺栓塞和术后出血发生率、再手术率、术后拔除引流管、胃管时间和术后住院时长比较,差异均无统计学意义(P值均>0.05)。两组间肿瘤各T分期、N分期患者占比及肿瘤伴周围脂肪浸润率比较,差异均有统计学意义(P值均<0.01);两组间肿瘤直径、肿瘤各M分期患者占比及肿瘤伴脉管浸润率比较,差异均无统计学意义(P值均>0.05)。截至2022年10月30日,侵袭性IPMN组中,术后复发或转移23例;接受术后辅助治疗48例,均接受化疗,其中有9例接受了放射治疗,6例接受了阿帕替尼、尼妥珠单抗等靶向治疗或替雷丽珠单抗等程序性死亡受体1(PD-1)抑制剂治疗。侵袭性IPMN组中位生存时间为1034(819,1106)d,PDAC组为919(876,980)d,两组间中位生存时间的差异无统计学意义(P=0.82)。多因素logistic回归分析结果显示,年龄为侵袭性IPMN患者生存时间的影响因素(P=0.003)。结论侵袭性IPMN患者的肿瘤分期较PDAC患者更早,但侵袭性IPMN与PDAC患者间无明显生存差异。

Objective To investigate the survival differences between invasive intraductal papillary mucinous neoplasm(inv-IPMN)and pancreatic ductal adenocarcinoma(PDAC).Methods We performed a retrospective analysis involving 91 inv-IPMN patients and 893 PDAC patients who underwent surgery from January 2012 to June 2022 at Zhongshan Hospital of Fudan University and had complete clinical data.The patients were diagnosed as PDAC or inv-IPMN by postoperative pathology.PDAC patients underwent chemotherapy additionally.Baseline information(gender,age,initial symptoms,history of diabetes,American Society Anesthesiologists[ASA]classification,preoperative carbohydrate antigen 19-9[CA19-9]level),operative status(duration of surgery,intraoperative blood loss,surgical method,arterial and venous invasion),postoperative complications(pancreatic fistula,gastroparesis,pulmonary embolism,and bleeding),reoperation rate,the time of postoperative drainage and gastric tube removal,length of hospital stay,postoperative pathological characteristics(tumor diameter,TNM stage,peripheral fatty infiltration,and vascular infiltration),recurrence or metastasis,and adjuvant therapy were analyzed.The survminer package of Rstudio 4.22 was used to plot survival curve which was analyzed using the Kaplan-Meier method and Log-Rank test.Cox risk regression models were used for univariate and multifactorial logistic regression analysis of factors influencing survival time in patients with inv-IPMN.Results There were significant differences in the age of patients,the proportion of patients with each first symptom,preoperative CA19-9 level,surgical methods and venous invasion between inv-IPMN group and PDAC group(P<0.05 or 0.01).There was no significant difference in the duration of surgery,intraoperative blood loss,or arterial invasion between the two groups(all P>0.05).There were significant differences in the incidence of pancreatic fistula and gastroparesis between the two groups(P<0.01 or 0.05),but there was no significant difference in the incidence of postoperative pulmonary embolism or hemorrhage,the reoperation rate,the time to remove the gastric tube,or postoperative hospital stay between the two groups(all P>0.05).There were significant differences in the proportion of patients with each T-stage and N-stage and the rate of peripheral fatty infiltration between the two groups(all P<0.01).There was no significant difference in the tumor diameter,the proportion of patients with each M-stage,or the rate of vascular infiltration between the two groups(all P>0.05).As of October 30,2022,recurrence or metastasis occurred in 23 patients in the inv-IPMN group,and postoperative adjuvant therapy was applied in 48 patients(chemotherapy in all the 48 patients,radiation therapy in 9,and targeted therapy such as apatinib and nitrozumab or immunosuppressive therapy such as tirelizumab in 6).The median survival time was 1034(819,1106)d in the inv-IPMN group and 919(876,980)d in the PDAC group(P=0.82).Multifactorial logistic regression analysis showed that age was an influencing factor for survival time in patients with inv-IPMN(P=0.003).Conclusion Patients with inv-IPMN have earlier tumor stage than patients with PDAC,but there is no significant survival difference between patients with inv-IPMN and PDAC.