title: Rates and patterns of recurrence after curative intent resection for gallbladder cancer: a multi-institution analysis from the US Extra-hepatic Biliary Malignancy Consortium.
abstract: Gallbladder cancer is a relatively rare malignancy. The current study aimed to define the incidence and patterns of recurrence following gallbladder cancer resection.
  
  
  
  Using a multi-institutional cohort we identified 217 patient undergoing curative intent surgery for gallbladder cancer. Patterns of recurrence were classified as locoregional and distant recurrence.
  
  
  
  At last follow-up, 76 patients (35.0%) had experienced a recurrence (locoregional only, n = 12, 15.8%; distant only, n = 50, 65.8%; locoregional and distant, n = 14, 18.4%). Median time to recurrence was 9.5 months (IQR 4.7-17.6) and was not associated with recurrence site (all p > 0.05). On multivariable analysis, T3 disease (HR = 8.44, p = 0.014), lymphovascular invasion (HR = 4.24, p < 0.001) and residual disease (HR = 2.04, p = 0.042) were associated with an increased risk of recurrence. Patients who recurred demonstrated a worse 1-, 3- and 5-year OS (1-year OS: 91.3% vs. 68.6%, p = 0.001, 3-year OS: 79.3% vs. 28.7%, p < 0.001, and 5-year OS: 75.9% vs. 16.0%, p < 0.001). After adjusting for other risk factors, recurrence was independently associated with a decreased OS (HR = 3.71, p = 0.006). Of note, receipt of adjuvant therapy was associated with improved OS (HR = 0.56, p = 0.027) among those patients who developed a tumor recurrence.
  
  
  
  Over one-third of patients experienced a recurrence after gallbladder cancer surgery. While chemotherapy did not decrease the rate of recurrence, patients who experienced recurrence after administration of adjuvant treatment faired better than patients who did not receive adjuvant therapy.
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Georgios Antonios
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Faiz
authors.initials: F
authors.lastname: Gani
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Buettner
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Amini
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Andreatos
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Cecilia G
authors.initials: CG
authors.lastname: Ethun
authors.affiliation: Department of Surgery, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Poultsides
authors.affiliation: Department of Surgery, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: Thuy
authors.initials: T
authors.lastname: Tran
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kamran
authors.initials: K
authors.lastname: Idrees
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Chelsea A
authors.initials: CA
authors.lastname: Isom
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Krasnick
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salem
authors.affiliation: Department of Surgery, University of Louisville, Louisville, KY, USA.
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
authors.affiliation: Department of Surgery, University of Louisville, Louisville, KY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Scoggins
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Perry
authors.initials: P
authors.lastname: Shen
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Harveshp D
authors.initials: HD
authors.lastname: Mogal
authors.affiliation: Department of Surgery, Ohio State University, Columbus, OH, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, Ohio State University, Columbus, OH, USA.
authors.forename: Eliza
authors.initials: E
authors.lastname: Beal
authors.affiliation: Department of Surgery, New York University, New York, NY, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Hatzaras
authors.affiliation: Department of Surgery, New York University, New York, NY, USA.
authors.forename: Rivfka
authors.initials: R
authors.lastname: Shenoy
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Surgery, Ohio State University, Columbus, OH, USA. Electronic address: tim.pawlik@osumc.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002763:Cholecystectomy / Q000009:adverse effects* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005706:Gallbladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States