胰腺神经内分泌肿瘤肝转移患者手术治疗与非手术治疗的预后分析研究

Prognosis Analysis of Surgical and Non-surgical Treatment for Patients with Pancreatic Neuroendocrine Tumor with Liver Metastasis

背景胰腺神经内分泌肿瘤相对罕见,但在疾病进展过程中可发生局部淋巴结、肝、肺和骨转移,以肝转移最为常见,约有50%患者容易发生肝转移,治疗方式影响患者的生存率,对患者的生命质量有一定的影响。目的探讨胰腺神经内分泌肿瘤肝转移患者手术治疗对预后的影响,为临床决策提供参考依据。方法选取2004-2013年SEER数据库中胰腺神经内分泌肿瘤的数据,纳入476例胰腺神经内分泌肿瘤肝转移患者。根据患者是否切除原发性肿瘤,将其分为手术治疗组和非手术治疗组。提取患者基线资料和临床特征,研究的终点是总体生存时间。结果 476例患者中,手术治疗组125例(26.3%),非手术治疗组351例(73.7%)。手术治疗组生存时间长于非手术治疗组(χ~2=57.649,P=0.001)。将患者分别按照T分期、淋巴结转移和组织学分化程度进行分层分析,结果显示,T1、T2、T3期患者中,手术治疗组生存时间均长于非手术治疗组(χ~2=5.543,P=0.019;χ~2=11.494,P=0.001;χ~2=34.240,P<0.001)。有淋巴结转移和无淋巴结转移患者中,手术治疗组生存时间均长于非手术治疗组(χ~2=29.392,P<0.001;χ~2=30.722,P<0.001)。组织学分化程度Ⅰ~Ⅱ级和Ⅲ~Ⅳ级患者中,手术治疗组生存时间均长于非手术治疗组(χ~2=18.513,P<0.001;χ~2=11.219,P<0.001)。多因素Cox比例风险回归模型结果显示,年龄>60岁〔HR=1.973,95%CI(1.476,2.637)〕、组织学分化程度为Ⅲ级或Ⅳ级〔HR=3.864,95%CI(2.279,6.551);HR=2.801,95%CI(1.278,6.141)〕、非手术治疗〔HR=4.845,95%CI(2.853,8.226)〕是胰腺神经内分泌肿瘤肝转移患者预后的独立危险因素(P<0.05)。结论胰腺神经内分泌肿瘤肝转移患者的手术切除提高了生存率。淋巴结转移和不同T分期与生存率无关,而年龄和组织学分化程度对生存率有显著影响。对于年龄<60岁的胰腺神经内分泌肿瘤肝转移患者,原发性肿瘤切除术应被视为治疗策略。

Background Pancreatic neuroendocrine tumors(PNETs) are relatively rare,but local lymph nodes,liver,lung and bone metastases can occur during disease progression,and among them liver metastasis is the most common.About 50% of patients are prone to liver metastasis.Treatment method affects the survival of such patients.Moreover,it can also influence the patient’s quality of life to a certain degree.Objective To explore the effect of surgical treatment on the prognosis of patients with pancreatic neuroendocrine tumor with liver metastasis,providing a reference for clinical treatment selection for this disease.Methods Data about PNETs between 2004 and 2013 were obtained from the SEER database.A total of 476 cases with liver metastasis were enrolled,of whom those receiving surgical treatment for removing the primary tumor,and those receiving non-surgical treatment were assigned to surgical group,and non-surgical group,respectively.Baseline and clinical data were analyzed.The endpoint of the study was overall survival.Results Of the participants,125(26.3%) received surgical treatment,and other 351(73.7%) did not.The average survival time of the surgical group was longer than that of non-surgical group(χ~2=57.649,P=0.001).Subgroup analysis stratified by T-stage showed that,longer average survival time was found in T1,T2,T3 patients with surgical treatment instead of those without non-surgical treatment,respectively(χ~2=5.543,P=0.019;χ~2=11.494,P=0.001;χ~2=34.240,P<0.001).Subgroup analysis by lymph node metastasis found that,surgical treatment was associated with longer average survival time either in those with lymph node metastasis(χ~2=29.392,P<0.001) or those without(χ~2=30.722,P<0.001).Subgroup analysis by grade of histological differentiation demonstrated that,surgical treatment was associated with longer average survival time in those with grade Ⅰ-Ⅱ(χ~2=18.513,P<0.001) and also in those with grade Ⅲ-Ⅳ(χ~2=11.219,P<0.001).Multivariate Cox proportional hazards regression analysis revealed that older than 60 years[HR=1.973,95%CI(1.476,2.637)],histological differentiation grade Ⅲ or Ⅳ[HR=3.864,95%CI(2.279,6.551);HR=2.801,95%CI(1.278,6.141)],and non-surgical treatment[HR=4.845,95%CI(2.853,8.226)]were independent risk factors for prognosis(P<0.05).Conclusion Surgical resection of the primary tumor improves survival.Lymph node metastasis and T-stage were not associated with the survival,but age and tumor histological differentiation had a significant effect on the survival.For patients younger than 60 years,surgical resection of the primary tumor should be considered a treatment strategy.