Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Mucosa
 The
 Esophagogastric  Junction
 Barrett's
 Esophagus

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OESO©2011
 
Volume: Barrett's Esophagus
Chapter: Treatments
 

Should the very variable thickness of Barrett's epithelium be considered when evaluating the results of photodynamic therapy?

P. Chandrasoma, K. Wickramasinghe (Los Angeles)

Exact anatomic measurements of the thickness of the layers of the esophagus have assumed importance recently with the emergence of new diagnostic and therapeutic modalities. Diagnostic modalities such as endoscopic ultrasound and the potential use of high wavelength acoustic microscopy, and therapeutic modalities such as mucosal ablation and endoscopic mucosal resection demand exact data on mucosal thickness in both health and disease. Such measurements are not easily available. Routine specimens of the esophagus at autopsy and surgery are associated with artifact induced by shortening and thickening of the esophagus secondary to muscle contraction that makes measurement inaccurate. Shortening tends to be greatest in the muscle layer.

Mucosal shortening occurs to a lesser extent due to contraction of the muscularis mucosae. In addition, the range of thickness of the various layers in different individuals and disease processes complicates matters further.

Ablative techniques use different physical modalities

Multipolar electrocautery (MPEC) utilizes a standard electrocautery probe that burns the mucosa on contact. The thickness of burn achieved can be varied by changing the duration of contact [1].

Argon plasma coagulation is a form of electocoagulation which uses a probe through which a charged stream of ionized argon gas carries the electrical current to the mucosa. Contact with the mucosa is not required. Thickness of burn possible is limited by the fact that carbonization of the burnt mucosa impedes the passage of current [2].

Thermal lasers have been used for mucosal ablation. They generate heat and cause burning of tissues in a localized manner. Lasers vary according to their power output and wavelength, which determine the burning power and tissue penetrating capability. Argon lasers and potassium tytanil phosphate-YAG lasers have limited depth of penetration whereas Nd:YAG lasers permit deeper tissue penetration [3].

Photodynamic therapy depends on the selective uptake of porphyrin derivatives (hematoporphyrin derivative, PhotofrinŽ, amino-levulinic acid) by dysplastic and neoplastic tissues. These agents cause photosensitization of the cells which make them susceptible to necrosis when exposed to light [4]. The photoradiation of the mucosa, usually with red light at 630 nm, is done via a special cylindrical diffusing fiber positioned in the center of the esophageal lumen. The selective uptake of the photosensitizer restricts damage to abnormal epithelial cells but the depth of penetration of the light is variable. In particular, the presence of mucosal folds results in some parts of the mucosa being shielded from the light and therefore protected from ablation.

Esophageal mucosal thickness measurements

The normal squamous epithelium is generally flat with a thin lamina propria and a thin but well defined double layered muscularis mucosae that represents the deepest mucosal layer. The submucosa separates the mucosa from the muscularis externa. Acid reflux produces significant changes in the mucosa of the esophagus. Damage to the mucosa by acid reflux may result in ulceration with associated fibrosis of the mucosa, submucosa and muscle layers with stricture formation. Both ulcerative and non-ulcerative esophagitis is associated with glandular transformation of the squamous epithelium characterized by cardiac mucosa with or without intestinal metaplasia (IM). Glandular mucosae vary from being atrophic to hyperplastic with marked reactive changes involving elongation of the foveolar region. The muscularis mucosae frequently becomes hyperplastic resulting in thickening, splitting and upward extension of muscle fibers into the lamina propria. It is not unusual to find mucosal glands, both cardiac and intestinal, entrapped in the thickened muscularis mucosae. We measured mucosal thickness in 10 patients who had esophagectomy in which Barrett's epithelium was present. Measurement in different areas were made, providing values for the least, mean, and greatest thickness of the entire mucosa and the depth of the glandular element (Table I). This showed a marked variation in both total mucosal thickness and glandular depth, both within different areas of the same esophagus and in different patients. The range of glandular depth varied between 0.3 mm and 1.3 mm in the entire group; in a single patient, the depth varied between 0.5 mm and 1.3 mm in two different areas of Barrett's mucosa.

Table I. Thickness of mucosa (from surface to deep aspect of muscularis mucosae) and thickness of glandular element in Barrett's esophagus, as measured in esophagectomy specimens. No attempt was made in these cases to prevent artifact resulting from postoperative muscle contraction.

At present, it is impossible to accurately gauge mucosal thickness at endoscopy from surface visualization. Endoscopic ultrasound is not sensitive enough to permit measurement of mucosal thickness and cannot be used simultaneously with ablative techniques. Endoscopic vision is limited to the surface epithelium, and the technique of ablation is blind to the vertical extent of the glandular mucosa. Once the surface has been ablated, it is very difficult to evaluate the presence or absence of residual glandular tissue in the deeper lamina propria. Ablation that is too superficial results in incomplete ablation of the glandular mucosa. Ablation that is too deep may damage the muscularis mucosae and muscularis externa and increase the risk of strictures. The variation in thickness of the glandular element and mucosa makes it impossible to develop any rules regarding the depth of ablation that is required.

Effects of ablative therapies

For these reasons, it is very likely that ablation of Barrett' mucosa is a misnomer. What is far more likely is that the ablation involves only the surface epithelium and a variable part of the superficial mucosa, leaving glands in the deeper mucosa intact. The damage is also very likely to be irregular. When ablation is coupled with antireflux treatment (surgery or effective acid suppression), the mucosa that regenerates is commonly squamous, leading to the endoscopic impression of cure [5]. However, what happens to the invisible remaining Barrett's glands in the deeper mucosa is unknown. What is clear is that if these glands remain viable, and if they already have their full complement of genetic hits that permits them to develop into neoplasms, the early recognition of such neoplasms by endoscopy will be more difficult because of the overlying squamous epithelium. Ablative techniques have been in use for too short a time for definitive conclusions to be made about these potential problems. Studies available todate suggest that it is common to have incomplete ablation of the Barrett's epithelium [1, 2, 5], and residual glands with IM are frequently present in the lamina propria overgrown by squamous epithelium on the surface [5] with all these ablative modalities. Cases have also been reported where there has been a progression from low to high-grade dysplasia after ablation [6].

References

1. Sampliner RE, Fennerty B, Garewal HS. Reversal of Barrett's esophagus with acid suppression and multipolar electrocoagulation: preliminary results. Gastrointestinal Endosc 1996;44:532-535.

2. Dumoulin FL, Terjung B, Neubrand M, Scheurlen C, Fischer HP, Sauerbruch T. Treatment of Barrett's esophagus by endoscopic argon plasma coagulation. Endoscopy 1997;29:751-753.

3. Barham CP, Jones RL, Biddlestone LR, Hardwick RH, Shepherd NA, Barr H. Photothermal laser ablation of Barrett's oesophagus: endoscopic and histological evidence of squamous re-epithelialization. Gut 1997;41:281-284.

4. Overholt BF, Panjehpour M. Photodynamic therapy for Barrett's esophagus. Gastrointestinal Endosc Clin North Am 1997;7:207-220.

5. Biddlestone LR, Barham CP, Wilkinson SP, Barr H, Shepherd NA. The histopathology of treated Barrett's esophagus: squamous reepithelialization after acid suppression and laser and photodynamic therapy. Am J Surg Pathol 1998;22:239245.

6. Maass S, Martin WR, Spiethoff A, Riemann JF. Barrett esophagus with seveer dysplasia in argon beam therapy. Zeitsch Gastroenterol 1998;36:301-306.


Publication date: August 2003 OESO©2011