title: Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric Study Suggesting a More Aggressive Behavior.
abstract: OBJECTIVE
  Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a very rare entity. The aim of this study was to revisit the features of a multicenter clinical series to identify significant prognostic factors.
  
  
  METHODS
  From January 2002 to December 2013, the clinical and pathological data of 23 patients (treated in five different institutions) were retrospectively reviewed. Survival analysis was performed to explore the relative weight of potential prognostic factors.
  
  
  RESULTS
  Median age and male/female ratio were 48 years and 14/9, respectively. Most (> 80%) of the patients presented with CS-related symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and central in 10 (43%). All patients but two (treated with chemotherapy) underwent surgical resection with curative intent. Definitive cyto/histology was indicative of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7 cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7 (∼ 30% of all cases). Four patients (22%) experienced a relapse of the disease after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%, better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as significant prognostic factors in this cohort of patients.
  
  
  CONCLUSIONS
  BCs causing CS are characterized by a high rate of lymph-nodal involvement, a suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of relapse even after radical resection. Advanced stage, lymph-nodal involvement and the persisting of the CS after treatment correlate with a poor prognosis.
authors.affiliation: Department of Thoracic Surgery, IRCCS Arcispedale Santa Maria Nuova Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Lococo
authors.affiliation: Department of General Thoracic Surgery, Catholic University, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Margaritora
authors.affiliation: Unit of Thoracic Surgery, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cardillo
authors.affiliation: Unit of Thoracic Surgery, University of Turin, Turin, Italy.
authors.forename: Perluigi
authors.initials: P
authors.lastname: Filosso
authors.affiliation: Department of General Thoracic Surgery, Catholic University, Rome, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Novellis
authors.affiliation: Department of Thoracic Surgery, IRCCS Arcispedale Santa Maria Nuova Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rapicetta
authors.affiliation: Unit of Thoracic Surgery, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carleo
authors.affiliation: Unit of Thoracic Surgery, University of Turin, Turin, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bora
authors.affiliation: International Research Activities Office and System Medicine, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cesario
authors.affiliation: Unit of Thoracic Surgery, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.affiliation: Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Thoracic Surgery, IRCCS Arcispedale Santa Maria Nuova Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Paci
mesh_terms: D000328:Adult; D001984:Bronchial Neoplasms / Q000150:complications* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002276:Carcinoid Tumor / Q000150:complications* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003480:Cushing Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D013908:Thoracotomy; D013997:Time Factors; D016896:Treatment Outcome