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

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OESO©2015
 
Volume: Barrett's Esophagus
Chapter: Dysplasia
 

What dosage of photosensitizer and wave-length is advisable?

B.F. Overholt (Knoxville)

High-grade dysplasia in Barrett's esophagus occurs sporadically in esophageal mucosa that is approximately twice as thick as normal esophageal mucosa. Hence, endoscopic ablative therapy must treat the entire Barrett's mucosal surface and produce adequate mucosal injury to destroy Barrett's mucosa including the deeper glands. The question addressed in this presentation speaks to the issue of the photosensitizers used for photodynamic therapy (PDT) in Barrett's dysplasia and does not address treating the entire mucosa.

Three photosensitizers have been studied for ablation of dysplastic Barrett's mucosa: 5aminolevulinic acid (ALA), porfimer sodium (PhotofrinŽ) and mTHPC (tetra-mhyhdroxyphenyl chlorin).

5-aminolevulinic acid-PDT (ALA-PDT) [1, 2]

ALA preferentially collects in mucosa with very little being found in submucosa or deeper structures. Therefore ALA-PDT produces mucosal ablation without the risk of deeper injury and subsequent esophageal stricture. Gossner [3] and Barr [4] treated a total of 15 patients with Barrett's dysplasia with ALA-PDT and reported complete elimination of dysplasia. However, the follow-up interval was short. In addition, follow-up biopsies demonstrated residual or subsquamous Barrett's mucosa in essentially all patients. Longterm results in these patients are awaited.

ALA, like all photosensitizers, is "activated" by multiple wavelengths of light. Photosensitizers absorb light at certain wavelengths better than others. The absorption of the wavelength of light creates singlet oxygen, a highly reactive radical that is cytotoxic and in vivo produces cell death. Although photosensitizer absorption of light at lower wavelengths (e.g. 340 nm) is significantly greater than at higher wavelengths (e.g. 635 nm), a practical decision balancing wavelength absorption and tissue penetration is made for each photosensitizer. Factored into this decision is the fact that light at lower wavelengths is limited to very superficial tissue penetration (e.g. mucosa only) resulting in superficial tissue necrosis. Longer wavelengths of light (e.g. 630 nm) penetrate with a much deeper biologic effect and therefore produce deeper necrosis. For ALA-PDT, the generally accepted wavelength used in PDT is 635 nm. ALA is typically given orally, 30-60 mg/kg with 635 nm light being delivered endoscopically 4 hours later.

Sodium porfimer-PDT (PhotofrinŽ-PDT) [5-7]

PhotofrinŽ collects in all tissues including all layers of the esophageal wall. Hence, the relatively deep penetration of red (630 nm) light which is used with PhotofrinŽ-PDT will produce photochemical tissue destruction much deeper than seen with ALA-PDT. Using standard light dosimetry of 200 J/cm of cylindrical diffuser, 630 nm light will produce mucosal and to a degree, submucosal, tissue necrosis. The results are as predicted: greater tissue destruction, greater ablation of Barrett's mucosa (both normal and dysplastic) and less residual and subsquamous Barrett's mucosa (4%). However, the deeper injury is associated with a 30% incidence of stricture formation following PhotofrinŽ-PDT as well as greater short-term side effects including chest pain, odynophagia and fever. PhotofrinŽ is administered i.v. at 2 mg/kg with 630 nm light delivered during endoscopy 48-72 hours later.

mTHPC-PDT [2, 8]

This chlorin derivative has a strong absorption peak at 652 nm and has a much higher singlet oxygen yield than porfimer sodium. Thus, lower doses of both drug and of light energy are used with this photosensitizer. Nonetheless, 652 nm light penetrates more deeply and produces deeper necrosis so mTHPC is typically reserved for use in malignant lesions that penetrate into submucosa or deeper. MTHPC is typically administered in a dosage of 0.075 mg/kg i.v. with 652 nm light being endoscopically delivered 96 hours later.

References

1. Barr H. Barrett's esophagus; treatment with 5-aminolevulinc acid photodynamic therapy. Gastrointest Endosc Clin N Am 2000;10:421-437.

2. Bown SG, Lovat LB. The biology of photodynamic therapy in the gastrointestinal tract. Gastrointest Endosc Clin N Am 2000;10:533-550.

3. Gossner L, Stolte M, Sroka R, Rick K, May A, Hahn EG,Ell C. Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevulinic acid. Gastroenterology 1998;114:448-455.

4. Barr H, Shepherd NA, Robert DJH, et al. Eradication of high grade dysplasia in columnar lined (Barrett's) esophagus by photodynamic therapy with endogenously generated protoporphyrin IX. Lancet 1996;348:584-585.

5. Overholt BF, Panjehpour M, Haydek J. Photodynamic therapy for Barrett's esophagus:follow up in 100 patients. Gastrointest Endosc 1999;49:1-7.

6. Panjehpour M, Overholt BF, Haydek JM, Lee SG. Results of photodynamic therapy for ablation of dysplasia and early cancer in Barrett's esophagus and effect of oral steroids on stricture formation. Am J Gastroenterol 2000;95:2177-2184.

7. Wang KK. Photodynamic therapy of Barrett's esophagus. Gastrointest Endosc Clin N Am 2000;10:409-419.

8. Ell C, Gossner L, May A, et al. Photodynamic ablation of early cancers of the stomach by means of mTHPC and laser irradiation:preliminary clinical experience. Gut 1998;43:345-349.


Publication date: August 2003 OESO©2015