title: Medically managed hypercholesterolemia and insulin-dependent diabetes mellitus preoperatively predicts poor survival after surgery for pancreatic cancer.
abstract: BACKGROUND
  Although patients with pancreatic ductal adenocarcinoma (PDAC) frequently require medications to treat pre-existing conditions, the impact of these treatments on outcomes post-resection is unknown. The purpose of this study was to determine the impact of preoperative medications on overall survival after pancreatic resection.
  
  
  METHODS
  Multi-institutional data on preoperative medications and outcomes in patients undergoing resection for PDAC were analyzed. Univariate and multivariate analyses were performed to determine which medications were predictive of early mortality.
  
  
  RESULTS
  Of the 518 patients resected for PDAC, 13.3% were being treated preoperatively with insulin, 14.8% were on a statin, 1.7% were on steroids, and 7.6% were on thyroxin. On univariate analysis, patients taking preoperative insulin had a higher 90-day mortality rate relative to those not on insulin (13.0% vs. 4.8%, p = 0.024), and those on a statin had a higher 90-day mortality than those who were not (10.8% vs. 4.6%, p = 0.035). Preoperative steroids and thyroxin were not associated with 90-day mortality (p = 0.409 and p = 0.474, respectively). Insulin and statin use was a stronger predictor of 90-day mortality than history of diabetes (p = 0.101), BMI ≥ 30 (p = 0.166), cardiac disease (p = 0.168), pulmonary disease (p = 1.000), or renal dysfunction (p = 1.000). Older patients also had a higher risk of early postoperative death (p = 0.011). On multivariate analysis, only preoperative insulin usage and statin treatment independently predicted early mortality (odds ratio (OR) = 3.043; 95% confidence interval (CI), 1.256-7.372; p = 0.014, and OR = 2.529; 95% CI, 1.048-6.104; p = 0.039, respectively). Based on the beta coefficients, a simple scoring system was devised to predict survival after resection from preoperative medication use. Zero points were assigned to patients who were on neither insulin nor a statin, one point to those who were on one or the other, and two points to those who were on both insulin and a statin. The score correlated with early postoperative survival (90-day mortality rates of 3.4%, 11.5%, and 13.3% for 0, 1, and 2 points, respectively, p = 0.004). Increasing score was also associated with poorer long-term outcomes, with a median overall survival of 19.6, 15.6, and 11.2 months for 0, 1, and 2 points, respectively (p = 0.002, median follow-up 14.4 months).
  
  
  CONCLUSIONS
  Patients with PDAC being treated for pre-existing diabetes or hypercholesterolemia with either insulin or statin-based therapy have an increased risk of early postoperative mortality. A simple scoring system based on preoperative medications can be used to predict early and overall survival following resection.
authors.affiliation: Surgery, University of Western Ontario, London, ON, Canada.
authors.forename: Ryaz B
authors.initials: RB
authors.lastname: Chagpar
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ahmad
authors.forename: Hong Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Christopher
authors.initials: C
authors.lastname: Rupp
authors.forename: Sharon
authors.initials: S
authors.lastname: Weber
authors.forename: Andrew
authors.initials: A
authors.lastname: Ebelhar
authors.forename: Juliana
authors.initials: J
authors.lastname: Gilbert
authors.forename: Adam
authors.initials: A
authors.lastname: Brinkman
authors.forename: Emily
authors.initials: E
authors.lastname: Winslow
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
authors.forename: David
authors.initials: D
authors.lastname: Kooby
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Chu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications / Q000401:mortality* / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010180:Pancreatectomy / Q000009:adverse effects / Q000401:mortality*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000401:mortality* / Q000601:surgery; D011379:Prognosis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin