title: Liver Transplantation for Advanced Hepatocellular Carcinoma after Downstaging Without Up-Front Stage Restrictions.
abstract: BACKGROUND
  The incidence of hepatocellular carcinoma (HCC) continues to increase dramatically worldwide. Liver transplantation (LT) is now the standard and optimal treatment for patients with HCC in the setting of cirrhosis, but only for tumors within Milan criteria. In patients presenting beyond Milan criteria, locoregional therapy (LRT) can downstage to within Milan criteria for consideration for LT. Although controversial, the current study aims to evaluate the outcomes of LT in patients presenting with advanced-stage HCC who underwent downstaging and compare these outcomes with those of patients who met Milan criteria at presentation.
  
  
  METHODS
  Our protocol does not set a priori limitations as long as HCC is confined to the liver. In this retrospective study between January 1, 2002 and December 31, 2014, we reviewed outcomes associated with 284 patients who presented within Milan criteria and patients who presented with more-advanced stage tumor who were potential transplantation candidates. The patients with advanced disease were then subdivided into those who were within or beyond University of California San Francisco criteria. Imaging, details of LRT, recurrence, and survival were compared between the groups.
  
  
  RESULTS
  Sixty-three of 210 (30%) eligible patients were downstaged and underwent transplantation; 14 additional downstaged and listed patients were withdrawn for the following reasons: death while waiting (n = 4), disease progression (n = 8), development of other malignancy (n = 1), and declined LT (n = 1). Twelve patients underwent resection after downstaging and did not require LT. Survival for patients who were downstaged was similar to those who were within Milan criteria initially. Recurrence of HCC at 5 years was similar between groups (10.9% vs 10.8%; p = 0.84).
  
  
  CONCLUSIONS
  Patients with beyond-Milan criteria HCC who are otherwise candidates for LT should undergo aggressive attempts at downstaging without a priori exclusion. This highly selective approach allows for excellent long-term results, similar to patients presenting with earlier-stage disease.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO. Electronic address: chapmanw@wustl.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Sandra
authors.initials: S
authors.lastname: Garcia-Aroz
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Neeta
authors.initials: N
authors.lastname: Vachharajani
authors.affiliation: Department of Radiology, Washington University School of Medicine, St Louis, MO.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Fowler
authors.affiliation: Department of Radiology, Washington University School of Medicine, St Louis, MO.
authors.forename: Nael
authors.initials: N
authors.lastname: Saad
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Jason
authors.initials: J
authors.lastname: Wellen
authors.affiliation: Department of Medical Oncology, Washington University School of Medicine, St Louis, MO.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Adeel S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: M B Majella
authors.initials: MB
authors.lastname: Doyle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult