title: Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: a nationwide cohort study.
abstract: OBJECTIVE
  To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer.
  
  
  BACKGROUND
  There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurrence.
  
  
  METHODS
  This was a nationwide cohort study of 9333 patients, prospectively registered in the database of the Danish Colorectal Cancer Group and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable Cox regression analysis was used to adjust for confounding.
  
  
  RESULTS
  The incidence of AL was 6.4%, 744 patients died within 120 days. Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no association to AL [adjusted hazard ratio (HR) = 0.78; 95% confidence interval (CI): 0.55-1.12; P = 0.184]. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI: 1.13-1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI: 1.01-1.44; P = 0.042). In 2841 patients with stage III cancer, AL was associated with both decreased likelihood of receiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI: 0.45-0.74; P < 0.001) and a delay to initial administration (16 days; 95% CI: 12-20 days; P < 0.001).
  
  
  CONCLUSIONS
  AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.
authors.affiliation: From the Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark.
authors.forename: Peter-Martin
authors.initials: PM
authors.lastname: Krarup
authors.forename: Andreas
authors.initials: A
authors.lastname: Nordholm-Carstensen
authors.forename: Lars N
authors.initials: LN
authors.lastname: Jorgensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Harling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000714:Anastomosis, Surgical / Q000009:adverse effects; D057868:Anastomotic Leak / Q000401:mortality*; D002423:Cause of Death / Q000639:trends; D003082:Colectomy / Q000009:adverse effects* / Q000379:methods; D003106:Colon / Q000601:surgery; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D016001:Confidence Intervals; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000209:etiology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D013997:Time Factors