title: CUP Syndrome in Neuroendocrine Neoplasia: Analysis of Risk Factors and Impact of Surgical Intervention.
abstract: BACKGROUND
  Neuroendocrine neoplasia (NEN) with unknown primary site (NEN-CUP tumors) may have a poor prognosis. We evaluated the clinical presentation, therapy, outcome, and risk factors for adverse outcomes in patients who had these tumors.
  
  
  METHODS
  In 243 patients who had NEN, a retrospective review was performed in 38 patients who had NEN-CUP tumors. The 38 patients who had NEN-CUP tumors were evaluated in three groups: group 1 (surgery; primary tumor detected; ten patients); group 2 (surgery; no primary tumor detected; ten patients); and group 3 (no surgery; 18 patients). Risk factors were evaluated with univariate and multivariate analyses.
  
  
  RESULTS
  Most patients who had NEN-CUP tumors [32 patients (84%)] had World Health Organization (WHO) performance score of 0 or 1, and most tumors [24 patients (63%)] were well differentiated (WHO grade, G1 or G2; Ki-67 index, ≤20%). Univariate analysis showed that greater survival was significantly associated with lower patient age, lower WHO performance score, lower WHO grade, lower number of metastatic sites, treatment with surgery, and no treatment with chemotherapy. Multivariate analysis showed that low WHO performance score (hazard ratio 7.63, 95% confidence interval (CI) 2.63-22.19) and treatment with surgery (hazard ratio 0.10, CI 0.028-0.381) were significant independent predictors of improved survival.
  
  
  CONCLUSIONS
  In patients with NEN-CUP tumors, surgical treatment is an independent predictor of better survival. Therefore, surgical treatment may be indicated in patients with good general health status and well-differentiated NEN-CUP tumors.
authors: Department for Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany, nehara.begum@gmx.de.
authors: Nehara
authors: N
authors: Begum
authors: Ulrich
authors: U
authors: Wellner
authors: Christoph
authors: C
authors: Thorns
authors: Georg
authors: G
authors: Brabant
authors: Martin
authors: M
authors: Hoffmann
authors: Conny Georg
authors: CG
authors: Bürk
authors: Hendrik
authors: H
authors: Lehnert
authors: Tobias
authors: T
authors: Keck
mesh_terms: D000367:Age Factors; D000368:Aged; D002277:Carcinoma / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D018358:Neuroendocrine Tumors / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013577:Syndrome