title: The Impact of Severe Anastomotic Leak on Long-term Survival and Cancer Recurrence After Surgical Resection for Esophageal Malignancy.
abstract: OBJECTIVE
  The aim of this study was to the determine impact of severe esophageal anastomotic leak (SEAL) upon long-term survival and locoregional cancer recurrence.
  
  
  BACKGROUND
  The impact of SEAL upon long-term survival after esophageal resection remains inconclusive with a number of studies demonstrating conflicting results.
  
  
  METHODS
  A multicenter database for the surgical treatment of esophageal cancer collected data from 30 university hospitals (2000-2010). SEAL was defined as a Clavien-Dindo III or IV leak. Patients with SEAL were compared with those without in terms of demographics, tumor characteristics, surgical technique, morbidity, survival, and recurrence.
  
  
  RESULTS
  From a database of 2944 operated on for esophageal cancer between 2000 and 2010, 209 patients who died within 90 days of surgery and 296 patients with a R1/R2 resection were excluded, leaving 2439 included in the final analysis; 208 (8.5%) developed a SEAL and significant independent association was observed with low hospital procedural volume, cervical anastomosis, tumoral stage III/IV, and pulmonary and cardiovascular complications. SEAL was associated with a significant reduction in median overall (35.8 vs 54.8 months; P = 0.002) and disease-free (34 vs 47.9 months; P = 0.005) survivals. After adjustment of confounding factors, SEAL was associated with a 28% greater likelihood of death [hazard ratio = 1.28; 95% confidence interval (CI): 1.04-1.59; P = 0.022], as well as greater overall (OR = 1.35; 95% CI: 1.15-1.73; P = 0.011), locoregional (OR = 1.56; 95% CI: 1.05-2.24; P = 0.030), and mixed (OR = 1.81; 95% CI: 1.20-2.71; P = 0.014) recurrences.
  
  
  CONCLUSIONS
  This large multicenter study provides strong evidence that SEAL adversely impacts cancer prognosis. The mechanism through which SEAL increases local recurrence is an important area for future research.
authors.affiliation: *Department of Surgery and Cancer, Imperial College, London, UK †Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France ‡North of France University, Lille, France §Inserm, UMR837, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis," JPARC, Lille, France ¶SIRIC OncoLille, Lille, France ||Department of Biostatistics, University Hospital, Lille, France **Departments of Digestive Surgery of Croix-Rousse University Hospital, Lyon, France ††Cavale Blanche University Hospital, Brest, France ‡‡Purpan University Hospital, Toulouse, France §§Saint Antoine University Hospital, Paris, France ¶¶Hautepierre University Hospital, Strasbourg, France ||||Pitié-Salpétrière University Hospital, Paris, France ***Edouard Herriot University Hospital, Lyon, France †††Louis Mourier University Hospital, Colombes, France ‡‡‡Vaudois University Hospital, Lausanne, Switzerland §§§ULB-Erasme-Bordet University Hospital, Bruxelles, Belgium ¶¶¶Pontchaillou University Hospital, Rennes, France ||||||Haut-Levêque University Hospital, Bordeaux, France.
authors.forename: Sheraz
authors.initials: S
authors.lastname: Markar
authors.forename: Caroline
authors.initials: C
authors.lastname: Gronnier
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mabrut
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bail
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carrere
authors.forename: Jérémie H
authors.initials: JH
authors.lastname: Lefevre
authors.forename: Cécile
authors.initials: C
authors.lastname: Brigand
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Vaillant
authors.forename: Mustapha
authors.initials: M
authors.lastname: Adham
authors.forename: Simon
authors.initials: S
authors.lastname: Msika
authors.forename: Nicolas
authors.initials: N
authors.lastname: Demartines
authors.forename: Issam El
authors.initials: IE
authors.lastname: Nakadi
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
authors.forename: Denis
authors.initials: D
authors.lastname: Collet
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057868:Anastomotic Leak; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000601:surgery; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis