Long-term results of ablation with antireflux surgery for Barrett's esophagus: a clinical and molecular biologic study.
BACKGROUND
The initial results from ablation therapy for metaplastic/dysplastic Barrett's esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported.


METHODS
Neodymium:yttrium-aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed.


RESULTS
At the end of the follow-up period (range, 3-15 years; mean, 8 years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5 cm; range 1-10 cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; P = 0.0002) and the proximal esophagus (1.8 vs. 0.95; P = 0.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; P = 0.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia.


CONCLUSIONS
The neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.
Division of General Thoracic and Esophageal Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 340, 00029 HUS Helsinki, Finland.
Tuuli
T
Kauttu
Jari
J
Räsänen
Leena
L
Krogerus
Eero
E
Sihvo
Pauli
P
Puolakkainen
Jarmo A
JA
Salo
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000535:Aluminum; D001471:Barrett Esophagus / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D000071616:CDX2 Transcription Factor; D003131:Combined Modality Therapy; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D018662:Fundoplication / Q000379:methods; D005764:Gastroesophageal Reflux / Q000150:complications / Q000378:metabolism / Q000601:surgery; D005978:Glutathione / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D053685:Laser Therapy / Q000379:methods*; D008297:Male; D008679:Metaplasia / Q000601:surgery; D018384:Oxidative Stress / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology; D012008:Recurrence; D013482:Superoxide Dismutase / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015019:Yttrium
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D016159:Tumor Suppressor Protein p53; C503779:yttrium-aluminum-garnet; D015019:Yttrium; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000535:Aluminum; D009195:Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D005978:Glutathione