title: Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma.
abstract: BACKGROUND
  The influence of jaundice on outcomes after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to determine, in a large multicentric series, the influence of severe jaundice (serum bilirubin level ≥250 μmol/L and 300 μmol/L) on early severe morbidity and survival after PD.
  
  
  METHODS
  From 2004 to 2009, twelve hundred patients (median age 66 years, 57% male) with resectable PDAC underwent PD. Patients who received preoperative biliary drainage for neoadjuvant treatment or cholangitis were excluded. Pre- and intraoperative data were collected by a standardized form. Serum bilirubin level and creatinine clearance were analyzed as categorical variables. Predictive factors of severe complications and poor survival (Kaplan-Meier method) were identified by univariate and multivariate analysis.
  
  
  RESULTS
  Median follow-up was 21 months (95% CI, 19-23). Operative mortality was 3.9% (n = 47), with no predictive factors in multivariate analysis. Severe complications (Dindo-Clavien grade III to IV) occurred in 22% (n = 268), with male sex (p = 0.025), America Society of Anesthesiologists score 3 to 4 (p = 0.022), serum bilirubin level ≥300 μmol/L (p = 0.034), and creatinine clearance <60 mL/min/1.73 m(2) (p = 0.013) identified as predictive factors in multivariate analysis. Overall 3-year survival rate was 41% (95% CI, 37-45%). In multivariate analysis, serum bilirubin level ≥300 μmol/L (p = 0.048), low-volume center (p < 0.001), venous resection (p = 0.014), N1 status (p < 0.01), R1 status (p < 0.001), and absence of adjuvant treatment (p < 0.001) negatively impacted survival. There was a negative relationship between survival at 12 months or later and higher rates of bilirubin. Presence of a biliary stent did not influence early or long-term results.
  
  
  CONCLUSIONS
  In this multicentric study, serum bilirubin level ≥300 μmol/L increased severe morbidity and decreased long-term survival after PD for PDAC. These findings suggest that biliary stenting is appropriately indicated before PD in patients with PDAC and severe jaundice.
authors.affiliation: Department of Hepato-Biliary and Pancreatic Surgery, Hôpital Beaujon, Clichy, France. Electronic address: alain.sauvanet@bjn.aphp.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.affiliation: Department of Biostatistics and Methodology, Institut Paoli Calmettes, Marseille, France; Unité Mixte de Recherche Institut de Recherche pour le Développement, Aix-Marseille University, Marseille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boher
authors.affiliation: Department of Digestive Surgery, Hôpital Saint Antoine, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Paye
authors.affiliation: Department of HPB Surgery, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bachellier
authors.affiliation: Centre Hépato-Biliaire, AP-HP, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sa Cuhna
authors.affiliation: Department of Surgery, Hôpital de la Conception, Marseille, France.
authors.forename: Yves-Patrice
authors.initials: YP
authors.lastname: Le Treut
authors.affiliation: Department of Surgery, Hôpital Edouard-Herriot, Lyon, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Adham
authors.affiliation: Department of Surgery, Hôpital de la Croix Rousse, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mabrut
authors.affiliation: Department of Surgery, Maison du Haut-Levêque, Pessac, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Chiche
authors.affiliation: Department of Surgical Oncology, Institut Paoli Calmettes, Marseille, France.
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Delpero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications / Q000401:mortality / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D041781:Jaundice, Obstructive / Q000150:complications* / Q000175:diagnosis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000150:complications / Q000401:mortality / Q000601:surgery*; D016577:Pancreaticoduodenectomy; D011183:Postoperative Complications / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome