Department of Surgery, City of Hope National Medical Center, Duarte, CA.
Department of Surgery, University of California, Irvine, CA.
Surgery. 2019 Apr;165(4):760-766. doi: 10.1016/j.surg.2018.10.018. Epub 2018 Nov 15.
The incidence of nonfunctional pancreatic neuroendocrine tumors ≤2cm is rising. The biologic behavior of these tumors is variable; thus, their management remains controversial. Chromogranin A upregulation is a useful diagnostic biomarker of neuroendocrine tumors; however, the prognostic significance of Chromogranin A is unclear. The objective of this study was to determine whether Chromogranin A levels have prognostic value in pancreatic neuroendocrine tumor patients and may help guide management.
We evaluated the National Cancer Database over a 10-year period (2004-2013). Patients with pancreatic neuroendocrine tumors measuring ≤2cm, without distant metastases, were identified and categorized as Chromogranin A high (>420ng/mL) or Chromogranin A low (≤420ng/mL), and those lacking data on Chromogranin A levels were excluded from the study. Univariate and multivariate analyses were performed using Cox proportional hazards model. Cut-point determination was performed using the Contal and O'Quigley method.
Of the 445 eligible patients, 352 (79%) were Chromogranin A low and 93 (21%) were Chromogranin A high. Median Chromogranin A level was 71ng/mL (interquartile range, 24-294ng/mL). Chromogranin levels were associated with clinical nodal status and grade. Furthermore, on multivariate analysis, Chromogranin A levels (Chromogranin A high versus Chromogranin A low) independently predicted overall survival after controlling for tumor size, grade, clinical nodal status, and academic status of the facility (hazard ratio: 7.90, 95%CI: 2.34-26.69, P = .001). The greatest benefit of surgical resection was noted in patients in the Chromogranin A high subgroup (log-rank P <.001).
Serum Chromogranin A levels can be incorporated in surgical decision-making for patients with small pancreatic neuroendocrine tumors. Patients in the Chromogranin A low group can be considered for observation, whereas patients in the Chromogranin A high group should be strongly considered for resection.
功能性胰腺神经内分泌肿瘤≤2cm 的发病率正在上升。这些肿瘤的生物学行为具有变异性，因此其治疗方法仍存在争议。嗜铬粒蛋白 A 上调是神经内分泌肿瘤的一种有用的诊断生物标志物；然而，嗜铬粒蛋白 A 的预后意义尚不清楚。本研究旨在确定嗜铬粒蛋白 A 水平在胰腺神经内分泌肿瘤患者中是否具有预后价值，并可能有助于指导治疗。
我们在 10 年期间（2004-2013 年）评估了国家癌症数据库。确定了无远处转移、肿瘤直径≤2cm 的胰腺神经内分泌肿瘤患者，并将其分为嗜铬粒蛋白 A 高（>420ng/mL）或嗜铬粒蛋白 A 低（≤420ng/mL）组，且缺乏嗜铬粒蛋白 A 水平数据的患者被排除在研究之外。使用 Cox 比例风险模型进行单变量和多变量分析。使用 Contal 和 O'Quigley 方法进行临界点确定。
在 445 名符合条件的患者中，352 名（79%）为嗜铬粒蛋白 A 低，93 名（21%）为嗜铬粒蛋白 A 高。中位嗜铬粒蛋白 A 水平为 71ng/mL（四分位距，24-294ng/mL）。嗜铬粒蛋白水平与临床淋巴结状态和分级相关。此外，多变量分析表明，在控制肿瘤大小、分级、临床淋巴结状态和医疗机构学术地位后，嗜铬粒蛋白 A 水平（嗜铬粒蛋白 A 高与嗜铬粒蛋白 A 低）独立预测总生存（风险比：7.90，95%CI：2.34-26.69，P=0.001）。在嗜铬粒蛋白 A 高亚组中，手术切除的获益最大（对数秩检验 P<0.001）。
血清嗜铬粒蛋白 A 水平可纳入小胰腺神经内分泌肿瘤的手术决策。嗜铬粒蛋白 A 低组患者可考虑观察，而嗜铬粒蛋白 A 高组患者应强烈考虑切除。
