The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.
BACKGROUND
Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD).


OBJECTIVE
To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies.


METHODS
In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry.


RESULTS
A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure.


CONCLUSIONS
Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.
Department of Anatomic Pathology, University of Genova and IRCCS S.Martino/IST University Hospital, Genoa, Italy.
L
L
Mastracci
Department of Anatomic Pathology, University of Genova and IRCCS S.Martino/IST University Hospital, Genoa, Italy.
R
http://orcid.org/0000-0002-8856-6185
R
Fiocca
Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
C
C
Engström
Department of Surgery, North Tyneside General Hospital, North Shields, UK.
S
S
Attwood
Department of Gastroenterology, Dr Horst Schmidt-Hospital, Wiesbaden, Germany.
C
C
Ell
Department of Gastroenterology and Hepatology, Nantes University and INSERM, Nantes, France.
J P
JP
Galmiche
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
J G
JG
Hatlebakk
AstraZeneca Gothenburg, Mölndal, Sweden.
G
G
Långström
AstraZeneca Gothenburg, Mölndal, Sweden.
S
S
Eklund
Formerly of AstraZeneca Gothenburg, Mölndal, Sweden.
T
T
Lind
Department of Surgery, Centre for Digestive Diseases, Karolinska University Hospital and CLINTEC, Karolinska Institutet, Stockholm, Sweden.
L
L
Lundell
D000328:Adult; D001706:Biopsy; D064098:Esomeprazole / Q000627:therapeutic use; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D010535:Laparoscopy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
D054328:Proton Pump Inhibitors; D064098:Esomeprazole