Cerullo Marcelo, Gani Faiz, Chen Sophia Y, Canner Joe, Pawlik Timothy M
Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA.
J Gastrointest Surg. 2016 Sep;20(9):1572-80. doi: 10.1007/s11605-016-3173-4. Epub 2016 Jun 2.
Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p = 0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.
临床前证据已证明二甲双胍具有抗肿瘤作用。然而，二甲双胍对胰腺癌的影响仍不明确。我们试图通过一个具有全国代表性的大型胰腺癌手术患者样本，评估二甲双胍使用与生存率之间的关联。利用Truven Health MarketScan数据库识别出在2010年1月1日至2012年12月31日期间接受胰腺切除术的患者。收集了临床数据，包括二甲双胍使用史，以及手术细节和长期预后信息。进行多变量Cox比例风险回归分析，以评估二甲双胍使用对总生存期（OS）的影响。共识别出3393例患者。患者的平均年龄为54.2岁（标准差=9.1岁）。约一半患者为女性（n = 1735，51.1%）；49.1%（n = 1665）的Charlson合并症指数为3或更高（CCI≥3）；19.6%（n = 664）患有糖尿病。手术时，60.0%（n = 2034）的患者接受了胰十二指肠切除术，35.7%（n = 1212）接受了部分/远端胰腺切除术，而4.3%（n = 147）接受了全胰腺切除术。病理检查显示，1057例（31.2%）有淋巴结转移。456例患者（13.4%）使用了二甲双胍，且在无局部晚期疾病的患者中更常用（14.3%对11.6%，p = 0.038）。虽然手术第一年患者的总生存期相当（1年时总生存期为65.4% [95%置信区间（CI）63.4 - 67.3%] 对69.2% [95% CI 64.2 - 73.4%]），但接受二甲双胍治疗的患者在术后18个月开始总生存期有所改善。在对患者和临床病理特征进行调整的多变量分析中，使用二甲双胍与死亡风险降低独立相关（风险比[HR]=0.7
