title: Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study.
abstract: Pancreatic adenocarcinoma (PDAC) incidence is increasing worldwide. Several studies have shown that lymphopenia was correlated with a poor prognosis but the potential interest to measure lymphopenia in the pre and post-operative setting as well as its added value among conventional prognostic factors was never investigated.
  
  
  
  Data from two independent cohorts in whom patients underwent resection for pancreatic carcinoma were retrospectively recorded. We examined the association between perioperative findings, pre and post-operative lymphocyte counts and overall survival (OS) in univariate and multivariate analyses. Performance assessment and internal validation of the final model were evaluated with Harrell's C-index, calibration plot and bootstrap sample procedures.
  
  
  
  Three hundred ninety patients were included in the analysis between 2000 and 2011. Pre and post-operative lymphocyte counts were independent prognostic factors associated with OS in multivariate analysis (p = 0.0128 and p = 0.0764, respectively). The addition of lymphocyte count variable to the conventional parameters identified in multivariate analysis (metastatic lymph node ratio, veinous emboli and adjuvant chemotherapy) significantly improved the model discrimination capacity (bootstrap mean difference = 0.04; 95 % CI, 0.01-0.06). The use of a threshold and combining the categorical (≥1000; <1000) information in pre and post lymphocyte counts permitted the identification of 4 subgroups of patients with different prognosis (p < 0.0001). Finally, the description of patients in long-term remission showed that only 3 of 65 (4.6 %) patients with post-operative lymphocyte count under 1000/mm3were alive 4 years after surgery contrary to 54 of 236 (22.8 %) patients with a post-operative lymphocyte count above 1000/mm3.
  
  
  
  Pre and post-operative lymphopenia are independent prognostic factors for OS and they have an additive value regarding conventional prognostic factors for death-risk stratification and to predict long-term survival. Lymphopenia should be included as stratification factors in future clinical trial assessing overall survival in pancreatic cancer patients.
authors: Department of Gastroenterology, University Hospital of Besançon, Besançon, France.
authors: Christelle
authors: C
authors: d'Engremont
authors: Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
authors: Dewi
authors: D
authors: Vernerey
authors: Department of Gastroenterology and GI oncology, Paris Descartes University, Georges Pompidou European Hospital, Paris, France.
authors: Anne-Laure
authors: AL
authors: Pointet
authors: Department of Digestive Surgery and Liver Transplantation, University hospital of Strasbourg, Strasbourg, France.
authors: Gaël
authors: G
authors: Simone
authors: Department of Gastroenterology, University Hospital of Besançon, Besançon, France.
authors: Francine
authors: F
authors: Fein
authors: Department of Digestive Surgery and Liver Transplantation, University Hospital of Besançon, Besançon, France.
authors: Bruno
authors: B
authors: Heyd
authors: Department of Gastroenterology, University Hospital of Besançon, Besançon, France.
authors: Stéphane
authors: S
authors: Koch
authors: Department of Gastroenterology, University Hospital of Besançon, Besançon, France.
authors: Lucine
authors: L
authors: Vuitton
authors: Department of Medical Oncology, University Hospital of Besançon, Besançon, France.
authors: Stefano
authors: S
authors: Kim
authors: Department of Medical Oncology, University Hospital of Besançon, Besançon, France.
authors: Marine
authors: M
authors: Jary
authors: Department of Digestive Surgery, Hospital of Belfort-Montbeliard, Montbeliard, France.
authors: Najib
authors: N
authors: Lamfichek
authors: Department of Digestive Surgery and Liver Transplantation, University Hospital of Besançon, Besançon, France.
authors: Celia
authors: C
authors: Turco
authors: Department of Digestive Surgery and Liver Transplantation, University Hospital of Besançon, Besançon, France.
authors: Zaher
authors: Z
authors: Lakkis
authors: Department of GI Surgery, Paris Descartes University, Georges Pompidou European Hospital, Paris, France.
authors: Anne
authors: A
authors: Berger
authors: Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
authors: Franck
authors: F
authors: Bonnetain
authors: Department of Gastroenterology and GI oncology, Paris Descartes University, Georges Pompidou European Hospital, Paris, France.
authors: Julien
authors: J
authors: Taieb
authors: Department of Digestive Surgery and Liver Transplantation, University hospital of Strasbourg, Strasbourg, France.
authors: Philippe
authors: P
authors: Bachellier
authors: Department of Medical Oncology, University Hospital of Besançon, Besançon, France. christophe.borg@efs.sante.fr.|Centre investigation Clinique en biothérapie, CIC-1431, Besançon, France. christophe.borg@efs.sante.fr.|UMR1098 INSERM/Université de Franche Comté/Etablissement Français du Sang, Besançon, France. christophe.borg@efs.sante.fr.|Department of Oncology, University Hospital of Besançon, 3 Boulevard Alexander Fleming, Besancon, F-25030, France. christophe.borg@efs.sante.fr.
authors: Christophe
authors: C
authors: Borg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000601:surgery; D011184:Postoperative Period; D057234:Preoperative Period; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012306:Risk
chemical_list: D015415:Biomarkers
keywords: Lymphocyte count; Lymphopenia; Pancreatic adenocarcinoma; Prognosis