The previous paradigm that Barrett's is an irreversible premalignant lesion has recently been challenged by a proliferation of reports documenting elimination of Barrett's by a variety of endoscopic techniques. Whether Barrett's is entirely eliminated is unknown as endoscopic biopsy samples the surface of the epithelium only. Numerous reports document underlying specialised columnar epithelium in many of these trials. Until now there have been no reports of pathological examination of the entire oesophagus as a specimen. This case documents complete elimination of intestinal metaplasia from the oesophagus and supports the biological plausibility of these research techniques.
- Barrett's oesophagus
- multipolar electrocoagulation
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Barrett's oesophagus is an acquired premalignant condition secondary to chronic gastro-oesophageal reflux disease.1The intestinalised columnar epithelium in Barrett's oesophagus can develop dysplasia which is the precursor of oesophageal adenocarcinoma. Over the past two decades, oesophageal adenocarcinoma has been the most rapidly rising of any malignancy2 and now accounts for more than 12 000 deaths per year in the USA.3
In the past, Barrett's oesophagus was thought to be an irreversible premalignant lesion, based on numerous studies showing little change in the length of Barrett's oesophagus with either pharmacological therapy (H2 receptor antagonists, proton pump inhibitors) or surgical antireflux therapy.4-6However, since 1994, there have been a number of reports of reversal of Barrett's oesophagus following endoscopic thermal (heater probe, multipolar electrocoagulation (MPEC), laser, argon plasma coagulation) and non-thermal (photodynamic therapy) injury in patients with either surgically or pharmacologically controlled acid reflux.7-22 Based on follow up endoscopic biopsies, many patients in these trials appear to have complete elimination of Barrett's oesophagus. However, endoscopic biopsies are limited in their depth and area of mucosal sampling. The possibility remains that there is residual Barrett's epithelium underlying the restored squamous epithelium—for example, within the ducts leading to the submucosal oesophageal glands. Indeed, this phenomenon has been documented in a number of series23-27 and it remains unclear whether Barrett's epithelium is ever fully eliminated.28-30 Here we report the histological findings in an oesophagectomy specimen from a patient who had received prior MPEC therapy for Barrett's oesophagus. The findings indicate that the premalignant Barrett's epithelium (intestinal metaplasia) can be completely eliminated by endoscopic MPEC therapy.
RB, a 29 year old male with severe reflux symptoms dating to his early teens, had Barrett's oesophagus confirmed histologically (intestinal metaplasia) at age 18. He underwent a Nissan fundoplication for symptom control but his reflux symptoms returned within six months of operation. He had yearly surveillance endoscopies for Barrett's oesophagus from 1989 until 1998, at which time he was referred by his gastroenterologist for inclusion into the MPEC-Barrett's ablation multicentre study.31 Following institution of omeprazole 40 mg twice daily for seven days, the patient had an initial protocol endoscopy in May 1998 which revealed 6 cm of Barrett's oesophagus. Barrett's was circumferential in its distal 3 cm with a 3 cm tongue occupying 25% of the mucosa in the proximal 3 cm (fig 1). Intestinal metaplasia without dysplasia was confirmed by biopsy. In addition, he had a large 4 cm hiatal hernia. The entire surface of the metaplastic Barrett's epithelium was treated with MPEC at a setting of 30 until whitening of the metaplastic epithelium was seen. Five follow up treatment sessions (with each session treating the entire residual surface of Barrett's) were performed from July 1998 to November 1998. His December 1998 follow up protocol endoscopy revealed a hiatal hernia but no apparent residual columnar mucosa in the tubular oesophagus (also absent by chromoendoscopy with Lugol's solution). Biopsies from oesophageal sites with prior metaplastic intestinal metaplasia revealed squamous mucosa only. By protocol, he was then placed on maintenance omeprazole 20 mg twice daily and follow up examination was planned for May 1999.
Despite control of his heartburn on this dose of proton pump inhibitor therapy, regurgitation persisted and he sought surgical therapy of his reflux disease. A laparoscopic “toupet-type” fundoplication (because of ineffective oesophageal peristalsis on oesophageal manometry) was performed in March 1999. The wrap became disrupted shortly after operation as a consequence of unremitting vomiting in the recovery room. He subsequently developed a symptomatic paraoesophageal hernia which necessitated open surgical repair in May 1999. At operation the intrathoracic oesophagus was fibrotic and friable with extensive adhesions to the pleura with penetration through into the lingula and left upper lobe requiring an oesophagogastrectomy for repair.
Following fixation in formalin, the entire distal oesophagus, including all areas previously involved by Barrett's, was submitted for histological review. Following intensive sectioning and search there was no residual intestinal metaplasia in the distal oesophagus (fig 2). At the squamocolumnar junction (identified by the submucosal gland) (fig 3), the columnar epithelium was free of goblet cells. The adjacent squamous epithelium was full thickness and showed minimal override of the columnar epithelium. There was some scarring of the submucosa and the squamous epithelium was thickened but there were no signs of intestinal metaplasia.
To our knowledge, this is the first documented case of complete elimination of Barrett's oesophagus following combination antireflux therapy and endoscopy thermal injury. This finding confirms the hypothesis that Barrett's oesophagus is a reversible premalignant lesion and complete elimination of Barrett's can occur within six months following therapy.7 8 30 Whether the majority of patients undergoing endoscopic ablation therapy have complete elimination of Barrett's oesophagus or whether this occurs in patients with dysplasia is not known. However, determination of this will be critical to document whether such therapies can decrease the risk of cancer or eliminate the need for further surveillance endoscopy.
The optimal form of endoscopic and/or antireflux therapy to affect reversal of Barrett's oesophagus is as yet unknown, as is whether elimination of this premalignant epithelium is durable and represents a cure of the lesion.30 32 33 The fibrotic and scarred oesophagus seen in this case raises concern as to transmural injury to adjacent organs from thermal ablation of Barrett's, the effect of which is unknown. This observation underscores the potential morbidity or hazards of th ese therapies and emphasises that until improvement in outcome is demonstrated, they remain research techniques. Additionally, Brandt et al have documented return of Barrett's oesophagus following cessation of pharmacological antireflux therapy after Barrett's had been apparently eliminated with endoscopic therapy.34 Thus lifelong pharmacological and/or surgical control of reflux may be necessary to avoid redevelopment of the metaplasia. Further data from resected and/or autopsy specimens following endoscopic ablative therapy are necessary to confirm the findings in this case. However, this report adds to a growing body of literature suggesting Barrett's oesophagus can be totally eliminated, and may be curable, in some patients by endoscopic therapy.
- Abbreviations used in this paper:
- multipolar electrocoagulation
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