title: Histology of symptomatic gastroesophageal reflux disease: is it predictive of response to proton pump inhibitors?
abstract: OBJECTIVE
  To examine the differences in esophageal histopathology between non-erosive reflux disease (NERD) and reflux esophagitis (RE), and to investigate whether baseline esophageal histopathology can predict the therapeutic response to proton pump inhibitors (PPIs).
  
  
  METHODS
  The subjects comprised 94 patients with NERD (n = 71) or mild RE (n = 23). Tissue was biopsied from 5 cm above the squamo-columnar junction (SCJ), and the degree or presence of nine histopathological markers was assessed. The patients were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. If complete heartburn relief was not achieved, RPZ was increased to 10 mg twice daily for another 2 weeks, and then to 20 mg twice daily for another 2 weeks if heartburn remained.
  
  
  RESULTS
  Features of esophageal histopathology 5 cm above the SCJ differed between NERD and RE patients. The esophageal histopathology in patients unresponsive to RPZ was characterized by Protein Gene Product (PGP) 9.5 negativity in those with NERD, and intraepithelial bleeding in those with RE. In addition, the combination of dilated intercellular spaces (DIS) (+)/PGP 9.5 (-) was indicative of strong resistance to PPI therapy in NERD patients.
  
  
  CONCLUSIONS
  The therapeutic efficacy of PPI can be predicted from the features of biopsied esophageal tissue. Factors predictive of resistance to treatment with PPI are negativity for PGP 9.5 in NERD patients and intraepithelial bleeding in RE patients.
authors.affiliation: Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. miwahgi@hyo-med.ac.jp
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
authors.forename: Kaiyo
authors.initials: K
authors.lastname: Takubo
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Shimatani
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Oshima
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Junko
authors.initials: J
authors.lastname: Aida
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Susumu
authors.initials: S
authors.lastname: Kurosawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Wada
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Habu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Michio
authors.initials: M
authors.lastname: Hongo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D004334:Drug Administration Schedule; D004942:Esophagitis, Peptic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D064750:Rabeprazole; D016896:Treatment Outcome; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D015415:Biomarkers; D054328:Proton Pump Inhibitors; C482860:UCHL1 protein, human; D064750:Rabeprazole; D043222:Ubiquitin Thiolesterase