title: Pancreatoduodenectomy associated complications influence cancer recurrence and time interval to death.
abstract: BACKGROUND
  Resection is the only life-prolonging option for pancreatic or periampullary cancer. Cell-mediated immunity might reduce progression of metastasis or local recurrence likelihood, but surgery associated morbidity can suppress this immunity. The aim of this study was to examine the influence of complications on cancer specific survival after pancreatoduodenectomy (PD) for pancreatic and periampullary cancer.
  
  
  METHODS
  517 consecutive patients who underwent PD for pancreatic or periampullary adenocarcinoma were analysed.
  
  
  RESULTS
  After median follow-up of 24 (14-44) months, 377 (73%) patients had died from progressive disease, 140 (27%) were alive. Median survival for pancreatic adenocarcinoma was 22 (18-25) months following an uncomplicated postoperative course versus 16 (13-19) months for patients with major surgical complications (p = 0.021). Multivariable Cox regression analysis demonstrated that microscopically residual disease (R1), complications, and adjuvant therapy were independent factors for recurrence. Within the R1 group, survival for patients with complications was even more limited, 9.7 (8.3-11.0) versus 18.7 (15.0-22.5) for those without (p < 0.001). For patients with R1 resection complications was the only independent predictor for a shorter time interval to death (hazard ratio 1.96; 95% CI 1.16-3.30). Complications did not influence survival of patients with periampullary adenocarcinoma.
  
  
  CONCLUSIONS
  Complications after resection are independently related to an impaired survival following PD for pancreatic, but not periampullary cancer. The effect is even more dramatic in patients who had an R1 resection. Although the relation is not causal per se, the findings support the hypothesis of a complication-induced, compromised immunity rendering patients more susceptible for recurrent disease.
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: navandergaag@gmail.com.
authors.forename: N A
authors.initials: NA
authors.lastname: van der Gaag
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Harmsen
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Eshuis
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: O R C
authors.initials: ORC
authors.lastname: Busch
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: van Gulik
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: d.j.gouma@amc.uva.nl.
authors.forename: D J
authors.initials: DJ
authors.lastname: Gouma
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000601:surgery*; D000368:Aged; D014670:Ampulla of Vater; D015331:Cohort Studies; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000601:surgery*; D005260:Female; D005746:Gastric Emptying; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D010185:Pancreatic Fistula; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000601:surgery*; D016577:Pancreaticoduodenectomy; D011183:Postoperative Complications; D019106:Postoperative Hemorrhage; D011379:Prognosis; D016016:Proportional Hazards Models; D013272:Stomach Diseases; D013997:Time Factors; D016896:Treatment Outcome
keywords: Complications; Pancreatic cancer; Pancreatoduodenectomy; Survival