Endoscopy 2002; 34(8): 611-616
DOI: 10.1055/s-2002-33247
Original Article
© Georg Thieme Verlag Stuttgart · New York

Is Topical δ-Aminolevulinic Acid Adequate for Photodynamic Therapy in Barrett’s Esophagus? A Pilot Study

M.-A.  Ortner 1 , K.  Zumbusch 1 , J.  Liebetruth 2 , B.  Ebert 3 , B.  Fleige 4 , M.  Dietel 4 , H.  Lochs 1
  • 1Department of Gastroenterology, Hepatology, Endocrinology, Metabolism and Nutrition, Medical Faculty Charité, Humboldt University, Berlin, Germany
  • 2Department of Surgery, Medical Faculty Charité, Humboldt University, Berlin, Germany
  • 3Department of Medical Physics and Metrological Information Technology, Physikalisch-Technische Bundesanstalt, Berlin, Germany
  • 4Department of Pathology, Medical Faculty Charité, Humboldt University, Berlin, Germany
Further Information

Publication History

Submitted 18 October 2001

Accepted after Revision 22 March 2002

Publication Date:
12 August 2002 (online)

Background and Study Aims: The methods of endoscopic ablation of metaplastic and dysplastic areas in Barrett’s esophagus so far described, are not satisfactory with respect to efficacy and safety. Therefore we investigated whether photodynamic therapy (PDT) with topical δ-aminolevulinic acid (δ-ALA) leads to ablation of specialized columnar epithelium and eradication of low-grade dysplasia while not producing phototoxicity and systemic side effects.

Patients and Methods: 14 patients with histologically proven Barrett’s esophagus, seven of whom had evidence of low-grade dysplasia, underwent endoscopic treatment with topical δ-ALA. Photoactivation (wavelength, 632 nm) was performed at 1.5 - 2 hours after drug administration using an argon dye laser. Patients received omeprazole 80 mg daily for 2 months; thereafter; maintenance therapy depended on reflux symptoms. Patients were endoscopically re-evaluated after 7 days, and subsequently at 3, 6, 12 and up to 48 months (mean follow up 33 months). Re-treatment with high-dose topical δ-ALA was offered to the 11 patients with remaining metaplasia and was carried out in five of them.

Results: Low-grade dysplasia was eradicated in all patients. One patient with no dysplasia before PDT developed a high-grade dysplasia after PDT. Complete ablation of Barrett’s metaplasia was observed in 21 % of the patients after the first treatment session and in 20 % after the second treatment session. The mean reduction in the length of Barrett’s metaplasia was 1.54 ± 1.29 cm after the first PDT session and 1.02 ± 0.80 cm after the second PDT session. Post-endoscopic pain and photosensitivity reactions were less frequent with low-dose δ-ALA PDT than with high-dose PDT (pain 15 %, 100 %, respectively; P = 0.001 by Fisher’s exact test; phototoxicity, 0 %, 50 %, respectively; P = 0.021 by Fisher’s exact test).

Conclusion: Low-dose topical administration of δ-ALA provides ablation of low-grade dysplasia in the range obtained with oral δ-ALA. In addition, it is safe and well tolerated. Since, however, topical administration of δ-ALA is not able to consistently eradicate Barrett’s esophagus, alternative methods will have to be developed.

References

  • 1 Barr H. Barrett’s esophagus: treatment with 5-aminolaevulinic acid photodynamic therapy.  Gastrointest Endosc Clin N Am. 2000;  10 421-437
  • 2 Overholt B F. Results of photodynamic therapy in Barrett’s oesophagus; a review.  Can J Gastroenterol. 1999;  13 393-396
  • 3 Montgomery E, Goldblum J R, Greenson J K. et al . Dysplasia as a predictive marker for invasive carcinoma in Barrett’s esophagus: a follow-up study based on 138 cases from a diagnostic variability study.  Hum Pathol. 2001;  32 379-388
  • 4 Weston A P, Sharma P, Topalovski M. et al . Long-term follow-up of Barrett’s high-grade dysplasia.  Am J Gastroenterol. 2000;  95 1888-1893
  • 5 Barbezat G O. New treatment for Barrett’s oesophagus.  Biomed Pharmacother. 2000;  54 362-367
  • 6 Overholt B F, Haggitt R C, Bronner M P. et al . A multicenter partially blinded, randomised study of the efficacy of photodynamic therapy (PDT) using porfimer sodium (POR) for the ablation of high-grade dysplasia (HGD) in Barrett's oesophagus (BE). Results of 5-month follow up.  Gastroenterology. 2001;  120 A79-A425
  • 7 Falk G W, Ours T M, Richter J E. Practice patterns for surveillance of Barrett’s esophagus in the United States.  Gastrointest Endosc. 2000;  52 197-203
  • 8 de Looze D. Endoscopic follow-up of Barrett’s esophagus.  Acta Gastroenterol Belg. 2000;  63 29-35
  • 9 Cameron A J. Management of Barrett’s esophagus.  Mayo Clin Proc. 1998;  73 457-461
  • 10 Skacel M, Petras R E, Gramlich T L. et al . The diagnosis of low-grade dysplasia in Barrett’s oesophagus and its implication for disease progression.  Am J Gastroenterol. 2000;  95 3383-3387
  • 11 Krishnadath K K, Wang K K, Taniguchi K. et al . Persistent genetic abnormalities in Barrett’s esophagus after photodynamic therapy.  Gastroenterology. 2000;  119 624-630
  • 12 Kessel D, Dougherty T J. Agents used in photodynamic therapy.  Rev Contemp Pharmacother. 1999;  10 19-24
  • 13 Koenig F, McGovern F J, Larne R. et al . Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid.  BJU Int. 1999;  83 129-135
  • 14 Messmann H, Kullmann F, Wild T. et al . Detection of dysplastic lesions by fluorescence in a model of colitis in rats after previous photosensitization with 5-aminolaevulinic acid.  Endoscopy. 1998;  30 333-338
  • 15 Ortner M, Ebert B, Nolte D. et al . Endoscopic investigation of Barrett's esophagus by laser induced fluorescence spectroscopy.  Endoscopy. 1997;  29 E1, 01
  • 16 Messmann H, Knuchel R, Baumler W. et al . Endoscopic fluorescence detection of dysplasia in patients with Barrett’s esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitisation.  Gastrointest Endosc. 1999;  49 97-101
  • 17 Ortner M A, Ebert B, Hein E. et al . Time-gated fluorescence spectroscopy in Barrett’s oesophagus.  Gut. 2002, Accepted for publication; 
  • 18 Barr H, Shepherd N A, Dix A. et al . Eradication of high-grade dysplasia in columnar-lined (Barrett’s) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX.  Lancet. 1996;  348 584-585
  • 19 Gossner L, Stolte M, Sroka R. et al . Photodynamic ablation of high-grade dysplasia and early cancer in Barrett’s esophagus by means of 5-aminolevulinic acid.  Gastroenterol. 1998;  114 448-455
  • 20 Ackroyd R, Brown N J, Davis M F. et al . Photodynamic therapy for dysplastic Barrett’s oesophagus: a prospective, double blind, randomised, placebo controlled trial.  Gut. 2000;  47 612-617
  • 21 Hinnen P, de Rooij F W, Terlouw E M. et al . Porphyrin biosynthesis in human Barrett’s oesophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid.  British J Cancer. 2000;  83 539-543
  • 22 Webber J, Kessel D, Fromm D. Side effects and photosensitization of human tissue after aminolaevulinic acid.  J Surg Res. 1997;  68 31-37
  • 23 Fritsch C, Verwohlt B, Bolsen K. et al . Influence of topical photodynamic therapy with 5-aminolaevulinic acid on porphyrin metabolism.  Arch Dermatol Res. 1996;  288 517-521
  • 24 Kennedy J C, Marcus S L, Pottier R H. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolaevulinic acid (ALA): mechanisms and clinical results.  J Clin Laser Med Surg. 1996;  14 289-304
  • 25 Reid B J, Hagitt R C, Rubin C E. et al . Observer variation in the diagnosis of dysplasia in Barrett’s esophagus.  Hum Pathol. 1998;  19 166-178
  • 26 Sagan C, Flejou J F, Diebold M D. et al . Reproducibility of histological criteria of dysplasia in Barrett's mucosa.  Gastroenterol Clin Biol. 1994;  18 31-34
  • 27 Wallace M B, Perelman L T, Backman V. et al . Endoscopic detection of dysplasia in patients with Barrett’s esophagus using light-scattering spectroscopy.  Gastroenterology. 2000;  119 677-682
  • 28 Veenhuizen R B, Stewart F A. The importance of fluence rate in photodynamic therapy: is there a parallel with ionising radiation dose-rate effects?.  Radiother Oncol. 1995;  37 131-135
  • 29 Sampliner R E, Fass R. Partial regression of Barrett’s esophagus is an inadequate endpoint.  Am J Gastroenterol. 1993;  12 2092-2094
  • 30 van Laethem J L, Peny M O, Salmon I. et al . Intramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett’s oesophagus.  Gut. 2000;  46 574-577
  • 31 Shand A, Dallal H, Plamer K. et al . Adenocarcinoma arising in columnar lined esophagus following treatment with argon plasma coagulation.  Gut. 2001;  48 580-581
  • 32 Curnow A, McIlroy B W, Postle-Hacon M J. et al . Light dose fractionation to enhance photodynamic therapy using 5-aminolaevulinic acid in the normal rat colon.  Photochem Photobiol. 1999;  69 71-76
  • 33 Lange N, Jichlinski P, Zellweger M. et al . Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study.  Br J Cancer. 1999;  80 185-193
  • 34 Overholt B F, Panjehpour M. Photodynamic therapy in Barrett’s oesophagus.  J Clin Laser Med Surg. 1996;  14 245-249
  • 35 Javaid B, Watt P, Krasner N. Photodynamic therapy (PDT) for oesophageal dysplasia and early carcinoma with mTHPC (m-Tetrahydroxyphenyl Chlorin): A preliminary study.  Laser Med Sci. 2002;  17 51-56

M.-A. Ortner, M.D.

Department of Gastroenterology, Hepatology, Endocrinology, Metabolism, and Nutrition · Medical Faculty Charité · Humboldt University

Schumannstrasse 20 - 21 · 10117 Berlin · Germany ·

Fax: + 49-30-28028978

Email: Marianne.Ortner@charite.de

    >