title: Mesenteric Fibrosis in Midgut Neuroendocrine Tumors: Functionality and Radiological Features.
abstract: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD).
  
  
  
  A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed.
  
  
  
  Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043).
  
  
  
  We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.
authors.forename: Víctor
authors.initials: V
authors.lastname: Rodríguez Laval
authors.forename: Marianne
authors.initials: M
authors.lastname: Pavel
authors.forename: Ingo G
authors.initials: IG
authors.lastname: Steffen
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Baur
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Dilz
authors.forename: Christian
authors.initials: C
authors.lastname: Fischer
authors.forename: Katharina
authors.initials: K
authors.lastname: Detjen
authors.forename: Vikas
authors.initials: V
authors.lastname: Prasad
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.forename: Dominik
authors.initials: D
authors.lastname: Geisel
authors.forename: Timm
authors.initials: T
authors.lastname: Denecke
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D005355:Fibrosis / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D047368:Tumor Burden
chemical_list: D006897:Hydroxyindoleacetic Acid
keywords: 5-Hydroxyindoleacetic acid; Carcinoid heart disease; Carcinoid syndrome; Gastroenteropancreatic neuroendocrine tumors; Imaging; Serotonin