Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
JAMA Surg. 2019 Oct 1;154(10):943-951. doi: 10.1001/jamasurg.2019.2272.
In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited.
To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017.
Pancreatic cancer surgery with or without NAT.
Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model.
Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002).
Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
重要性：在过去十年中，新辅助治疗（NAT）在边界性和局部晚期胰腺导管腺癌（PDAC）患者中的应用有所增加。关于这种情况下胰瘘和相关总生存（OS）的数据有限。
目的：比较接受 NAT 后行直接切除术或胰腺切除术的患者的术后并发症，重点关注临床上相关的胰瘘（CR-POPF）和与 OS 的潜在关联。
设计、设置和参与者：这项回顾性队列研究对 2007 年 1 月 1 日至 2017 年 12 月 31 日期间在马萨诸塞州综合医院接受 PDAC 胰腺切除术的患者的数据进行了分析。
暴露因素：接受或不接受 NAT 的胰腺癌手术。
主要结果和测量指标：比较 NAT 和直接切除术之间的总体发病率和 CR-POPF 发生率。通过单变量和多变量分析评估与 CR-POPF 相关的因素。通过 Kaplan-Meier 曲线和 Cox 比例风险回归模型分析生存数据。
结果：在 753 名患者中，364 名男性（48.3%）；中位（四分位间距）年龄为 68（61-75）岁。共有 346 名患者（45.9%）接受了 NAT，407 名患者（54.1%）接受了直接切除术。在病理检查中，NAT 与较小的肿瘤大小相关（平均[SD]，26.0[15.3]mm 与 32.7[14.4]mm；P<.001），淋巴结受累减少（102[25.1%]与 191[55.2%]；P<.001），以及更高的 R0 率（257[74.3%]与 239[58.7%]；P<.001）。严重并发症发生率或 90 天死亡率无显著差异。与直接切除术相比，接受 NAT 的患者发生 CR-POPF 的比例低 3.6 倍（13[3.8%]与 56[13.8%]；P<.001）。此外，NAT 后与 CR-POPF 相关的因素发生了变化，只有软胰腺质地与 CR-POPF 的风险增加相关（38.5%与 6.3%；P<.001）。生存分析显示，直接切除术后有无 CR-POPF 的患者之间无差异（26 与 25 个月；P=.66），但 NAT 后，CR-POPF 患者的总体生存率更差（17 与 34 个月；P=.002）。通过多变量分析，这种关联独立于其他总体生存的既定预测因素（风险比，2.80；95%CI，1.44-5.45；P<.002）。
结论和相关性：新辅助治疗可能与 CR-POPF 发生率的显著降低相关。此外，与 CR-POPF 相关的标准因素在接受 NAT 后似乎不再适用。然而，一旦发生 CR-POPF，就会显著降低长期生存率。发生 CR-POPF 的患者可能需要更密切的随访，并可能受益于额外的治疗。
