title: Esophageal cell proliferation in gastroesophageal reflux disease: clinical-morphological data before and after pantoprazole.
abstract: OBJECTIVE
  To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease (GERD).
  
  
  METHODS
  This was a single-blinded study for pH-monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment.
  
  
  RESULTS
  With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces (DIS). After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis (ERD) group.
  
  
  CONCLUSIONS
  Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.
authors.affiliation: Department of Clinical Medicine, University of Bologna, Bologna, Italy. carlo.calabrese2@unibo.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Calabrese
authors.forename: Davide
authors.initials: D
authors.lastname: Treré
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Liguori
authors.forename: Veronica
authors.initials: V
authors.lastname: Gabusi
authors.forename: Manuela
authors.initials: M
authors.lastname: Vici
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Derenzini
authors.forename: Giulio
authors.initials: G
authors.lastname: Di Febo
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004724:Endoscopy; D004947:Esophagus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005110:Extracellular Space; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018670:Monitoring, Ambulatory; D009092:Mucous Membrane / Q000473:pathology / Q000648:ultrastructure; D000077402:Pantoprazole; D016037:Single-Blind Method; D044767:Ubiquitin-Protein Ligases / Q000032:analysis; D014945:Wound Healing / Q000187:drug effects; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000077402:Pantoprazole; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases