目的 探讨血清嗜铬粒蛋白A(CgA)水平与无功能性胰腺神经内分泌瘤(pNETs)肝转移肿瘤负荷及患者预后的关系.方法 回顾性分析2011年12月至2013年12月复旦大学附属中山医院收治的64例无功能性pNETs肝转移患者的临床资料.39例患者具有临床和随访资料,25例患者仅有临床资料.64例患者中,58例具有尚未发生肝转移时的血清CgA水平资料,51例具有已发生肝转移时的血清CgA水平资料.采用门诊方式进行随访,患者出院后每3～6个月定期复查实验室和影像学检查.患者血清CgA水平升高或降低程度≥50％治疗肝转移瘤前的血清CgA水平,定义为血清CgA水平升高或降低,其余定义为血清CgA水平稳定.随访时间截至2014年3月.采用ELISA法检测血清CgA.CT检查三维重建测定肝转移肿瘤负荷.采用国际实体瘤疗效评价标准评价无功能性pNETs肝转移患者疗效.将完全缓解和部分缓解归为治疗缓解,疾病稳定归为疾病稳定,疾病进展和肿瘤复发归为疾病进展.计量资料用M(P25,P75)表示,计数资料检验采用Fisher确切概率法,计量资料多组间比较采用Kruskal-Wallis检验,两两比较采用Mann-Whitney检验,采用Spearman等级相关分析进行相关性检验.结果 无功能性pNETs肝转移患者血清CgA水平为94.8 μg/L(67.4 μg/L,181.4 μg/L),显著高于尚未发生肝转移时的血清CgA水平59.9 μg/L(39.1μg/L,88.5 μg/L),两者比较,差异有统计学意义(Z=-3.96,P＜0.05).无功能性pNETs肝转移患者血清CgA水平与无功能性pNETs肝转移肿瘤负荷呈正相关(r=0.486,P＜0.05).39例具有临床和随访资料的患者中35例获得完整随访,中位随访时间为10个月.14例治疗缓解的患者中,血清CgA水平降低和稳定患者比例分别为11/14和3/14;12例疾病稳定的患者中,血清CgA水平降低、稳定和升高的患者比例分别为4/12、7/12和1/12;9例疾病进展的患者中,血清CgA水平稳定和升高患者比例分别为2/9和7/9.3种不同疗效的患者血清CgA水平降低和升高患者比例比较,差异均有统计学意义(F =11.02,18.82,P＜0.05);血清CgA水平稳定患者比例比较,差异无统计学意义(F=5.68,P＞0.05).治疗缓解的患者血清CgA水平降低患者比例显著高于其余两种疗效的患者,差异有统计学意义(P＜0.05);疾病进展的患者血清CgA水平升高患者比例显著高于其余两种疗效的患者,差异有统计学意义(P＜0.05).结论 高血清CgA水平可能提示无功能性pNETs患者发生肝转移,疗效不佳.血清CgA水平越高,可能提示肝转移肿瘤负荷越大.%Objective To investigate the relationship between the level of serum chromogranin A (CgA) and liver metastases of non-functional pancreatic neuroendocrine tumors (pNETs).Methods The clinical data of 64 patients with non-functional pNETs who were admitted to the Zhongshan Hospital of Fudan University from December 2011 to December 2013 were retrospectively analyzed.Thirty-nine patients had complete clinical and follow-up data,and 25 patients only have clinical data.The levels of serum CgA were detected in 58 patients before liver metastases,and the levels of serum CgA were detected in 51 patients after liver metastases.Patients were re-examined every 3-6 months after the discharge.The level of serum CgA was increased or decreased by more than 50％ of the level of serum CgA before the treatment was defined as increase or decrease of serum CgA,otherwise,stable level of serum CgA.The levels of serum CgA were detected by enzyme-linked immunosorbent assay,and the liver metastatic tumor load was assessed by three-dimensional reconstruction with the data of computed tomography.The efficacy of treatment was evaluated by response evaluation criteria in solid tumors.Patients were followed up via out-patient examination till March 2014.Complete or partial remission was defined as disease remisson,stable condition was defined as stable disease,and disease progression or tumor recurrence was defined as disease progression.The measurement data were presented by (P25,P75).The count data were analyzed using the Fisher exact probability,and the measurement data were analyzed using the Kruskal-Wallis test or MannWhitney test.The correlation was tested by Spearman rank correlation.Results The levels of serum CgA of pNETs patients with liver metastases was 94.8 μg/L (67.4μg/L,181.4 μg/L),which was significantly higher than 59.9 μg/L (39.1 μg/L,88.5 μg/L) of pNETs patients without liver metastases (Z =-3.96,P ＜0.05).There was a positive correlation between the tumor load and the level of the serum CgA before liver metastases in 51 non-functional pNETs patients (r =0.486,P ＜ 0.05).Thirty-five patients were followed up for a median time of 10 months.In the 14 patients with disease remission,the ratios of patients with increased and stable level of serum CgA were 11/14 and 3/14,respectively.In the 12 patients with a stable condition,the ratios of patients with decreased,stable and increased level of serum CgA were 4/12,7/12 and 1/12,respectively.In the 9 patients with disease progression,the ratios of patients with stable and increased levels of serum CgA were 2/9 and 7/9,respectively.There were significant differences in the ratios of patients with decreased and increased levels of CgA among the 3 groups of patients (F =11.02,18.82,P ＜0.05),while no significant difference was detected in the ratio of patients with stable level of CgA among the 3 groups of patients (F =5.68,P ＞ 0.05).The ratio of patients with decreased level of serum CgA in patients with disease remission was significant higher than patients with disease progression or in a stable condition (P ＜ 0.05).The ratio of patients with increased level of serum CgA in patients with disease progression was significantly higher than patients with disease remission or in a stable condition (P ＜ 0.05).Conclusions Increased level of serum CgA might indicate that the efficacy of treatment is poor for non-functional pNETs patients with liver metastases.The tumor load is increased as the increase of the serum CgA level.
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