title: Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies.
abstract: BACKGROUND
  Current approaches to adjuvant treatment after resection of gallbladder carcinoma (GBCA) and hilar cholangiocarcinoma (HCCA) are based on an incomplete understanding of the recurrence patterns of these diseases. Through an in-depth analysis of the sites of initial recurrence after resection of GBCA and HCCA, the current study aimed to highlight differences in the biology of these tumors and to provide further insight for adjuvant therapeutic strategies.
  
  
  METHODS
  Patients with either GBCA or HCCA who underwent a potentially curative resection were identified prospectively from a maintained database. Specific sites of initial disease recurrence were identified retrospectively and categorized as locoregional (resection margin, porta hepatis, or retroperitoneal lymph nodes) or distant (peritoneal, extraabdominal, or discontiguous liver metastases). Differences in disease recurrence patterns, time to disease recurrence, and overall and site-specific survival were analyzed.
  
  
  RESULTS
  Between May 1990 and August 2001, 177 patients underwent potentially curative resection, 97 for GBCA and 80 for HCCA. Disease recurrence and follow-up data were available for 156 patients (80 with GBCA and 76 with HCCA). The median time to disease recurrence was shorter for patients with GBCA compared with patients with HCCA (11.5 vs. 20.3 months; P = 0.007). Overall, 52 (68%) patients with HCCA and 53 (66%) patients with GBCA had disease recurrene at a median follow-up of 24 months. Of those who developed disease recurrence, isolated locoregional disease as the first site of failure occurred in 15% of patients with GBCA compared with 59% of patients with HCCA (P < 0.001). By contrast, an initial GBCA recurrence involving a distant site, with or without concomitant locoregional recurrence, occurred in 85% of patients compared with 41% of patients with HCCA (P < 0.001). This pattern of disease recurrence was diagnosis specific and did not change significantly when patients were stratified by several clinicopathologic factors, including disease stage and its component variables. Using multivariate analysis, diagnosis was an independent predictor of the site of disease recurrence. Among patients who experienced disease recurrence, survival was greater among the patients with HCCA compared with patients with GBCA (29 months vs. 20.6 months, respectively; P = 0.037). For both tumors, the site of initial disease recurrence had no apparent impact on survival time.
  
  
  CONCLUSIONS
  After resection, recurrent GBCA is much more likely than recurrent HCCA to involve a distant site. GBCA is also associated with a much shorter time to recurrence and a shorter survival period after recurrence. The results demonstrated significant differences in the clinical behavior of these tumors and suggested that an adjuvant therapeutic strategy targeting locoregional disease, such as radiotherapy, is unlikely to have a significant impact in the overall management of GBCA. Conversely, there is at least some rationale for such an approach in patients with HCCA based on the pattern of initial recurrence.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. jarnagiw@mskcc.org
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Leyo
authors.initials: L
authors.lastname: Ruo
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Little
authors.forename: David
authors.initials: D
authors.lastname: Klimstra
authors.forename: Michael
authors.initials: M
authors.lastname: D'Angelica
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Raquel
authors.initials: R
authors.lastname: Wagman
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Blumgart
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D001653:Bile Ducts, Intrahepatic; D017024:Chemotherapy, Adjuvant; D018281:Cholangiocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D005260:Female; D005706:Gallbladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate