Abstract
Background: Barrett’s esophagus is the major risk factor for esophageal adenocarcinoma, the incidence of which is increasing rapidly in the Western world. Aminolevulinic acid for photodynamic therapy (ALA-PDT) is effective in the treatment of Barrett’s esophagus, but controversy exists regarding optimum ALA dosage. The aim of this study was to establish the optimum dosage regime for ALA-PDT for Barrett’s esophagus. Methods: Twenty-five patients with Barrett’s esophagus were randomized to receive 30 (low-dose) or 60 (high-dose) mg/kg oral ALA at 4 or 6 h or 30 mg/kg in two fractions 4 and 6 h before PDT. PDT was standardized using red (635 nm) light. Biopsy specimens were taken for protoporphyrin IX (PpIX) quantification. Endoscopy was repeated 4 weeks later. Results: All patients showed a macroscopic response, with squamous re-epithelialization. This response was greatest in the 30 mg/kg and fractionated ALA groups. There was no significant difference in response between dosing 4 or 6 h prior to PDT. Tissue levels of PpIX were similar for all dosage groups and were not predictive of clinical response. Side effects were more common with the higher dose of ALA. Conclusion: Low-dose ALA-PDT appears to be a safe protocol for the ablation of Barrett’s esophagus.


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References
R Ackroyd N Brown D Vernon D Roberts T Stephenson S Marcus C Stoddard M Reed (1999) ArticleTitle5-Aminolevulinic acid photosensitization of dysplastic Barrett’s esophagus: a pharmacokinetic study. Photochem Photobiol 70 656–662 Occurrence Handle1:CAS:528:DyaK1MXmvVahs70%3D Occurrence Handle10546561
R Ackroyd NJ Brown MF Davis TJ Stephenson SL Marcus CJ Stoddard AG Johnson MW Reed (2000) ArticleTitlePhotodynamic therapy for dysplastic Barrett’s oesophagus: a prospective, double blind, randomised, placebo controlled trial. Gut 47 612–617 Occurrence Handle10.1136/gut.47.5.612 Occurrence Handle1:CAS:528:DC%2BD3cXosVSgtbs%3D Occurrence Handle11034574
R Ackroyd CJ Kelty NJ Brown TJ Stephenson CJ Stoddard MW Reed (2003) ArticleTitleEradication of dysplastic Barrett’s esophagus using photodynamic therapy: long-term follow-up. Endoscopy 35 496–501 Occurrence Handle10.1055/s-2003-39676 Occurrence Handle1:STN:280:DC%2BD3s3ls1OrsQ%3D%3D Occurrence Handle12783347
H Barr NA Shepherd A Dix DJ Roberts WC Tan N Krasner (1996) ArticleTitleEradication of high-grade dysplasia in columnar-lined (Barrett’s) esophagus by photodynamic therapy with endogenously generated protoporphyrin IX. Lancet 348 584–585 Occurrence Handle10.1016/S0140-6736(96)03054-1 Occurrence Handle1:STN:280:BymA2s%2FmslI%3D Occurrence Handle8774572
J Bedwell AJ MacRobert D Phillips SG Bown (1992) ArticleTitleFluorescence distribution and photodynamic effect of ALA-induced PPIX in the DMH rat colonic tumour model. Br J Cancer 65 818–824 Occurrence Handle1:CAS:528:DyaK38Xlt1Ontro%3D Occurrence Handle1616853
AJ Cameron CT Lomboy M Pera HA Carpenter (1995) ArticleTitleAdenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology 109 1541–1546 Occurrence Handle1:STN:280:BymD3snjsVA%3D
SS Devesa WJ Blot JF Fraumeni Jr (1998) ArticleTitleChanging patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83 2049–2053
L Gossner M Stolte R Sroka K Rick A May EG Hahn C Ell (1998) ArticleTitlePhotodynamic ablation of high-grade dysplasia and early cancer in Barrett’s esophagus by means of 5-aminolevulinic acid. Gastroenterology 114 448–455 Occurrence Handle1:CAS:528:DyaK1cXhvVyhu7s%3D Occurrence Handle9496934
RC Haggitt (1994) ArticleTitleBarrett’s esophagus, dysplasia, and adenocarcinoma. Hum Pathol 25 982–993 Occurrence Handle1:STN:280:ByqD3M3itFA%3D Occurrence Handle7927321
P Hinnen F de Rooij W Hop A Edixhoven H van Dekken J Wilson P Siersema (2002) ArticleTitleTiming of 5-aminolaevulinic acid-induced photodynamic therapy for the treatment of patients with Barrett’s esophagus. J Photochem Photobiol B 68 8–14 Occurrence Handle10.1016/S1011-1344(02)00324-X Occurrence Handle1:CAS:528:DC%2BD38Xms1Oku7k%3D Occurrence Handle12208031
C Kelty R Ackroyd (2000) ArticleTitleRe-epithelialisation of Barrett’s oesophagus. Gut 47 741 Occurrence Handle10.1136/gut.47.5.741 Occurrence Handle1:STN:280:DC%2BD3M%2FjvVSmug%3D%3D
JC Kennedy RH Pottier (1992) ArticleTitleEndogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 14 275–292 Occurrence Handle1:CAS:528:DyaK38Xls1Klu70%3D Occurrence Handle1403373
OH Lowry NJ Rosebrough AL Fair RJ Randall (1951) ArticleTitleProtein measurement with the Folin phenol reagent. J Biol Chem 193 265–275 Occurrence Handle1:CAS:528:DyaG38XhsVyrsw%3D%3D
BF Overholt M Panjehpour JM Haydek (1999) ArticleTitlePhotodynamic therapy for Barrett’s esophagus: follow-up in 100 patients. Gastrointest Endosc 49 1–7
J Regula AJ MacRobert A Gorchein GA Buonaccorsi SM Thorpe GM Spencer AR Hatfield SG Bown (1995) ArticleTitlePhotosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX—a pilot study. Gut 36 67–75 Occurrence Handle1:STN:280:ByqC1MjgvVY%3D Occurrence Handle7890239
J van den Boogert HJ van Staveren RW de Bruin JH Eikelaar PD Siersema R van Hillegersberg (1999) ArticleTitlePhotodynamic therapy for esophageal lesions: selectivity depends on wavelength, power, and light dose. Ann Thorac Surg 68 1763–1769 Occurrence Handle10.1016/S0003-4975(99)01003-6 Occurrence Handle1:STN:280:DC%2BD3c%2FkvFOmsw%3D%3D Occurrence Handle10585056
JL Van Laethem MO Peny I Salmon M Cremer J Deviere (2000) ArticleTitleIntramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett’s oesophagus. Gut 46 574–577 Occurrence Handle10716690
R Waidelich H Stepp R Baumgartner E Weninger A Hofstetter M Kriegmair (2001) ArticleTitleClinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer. J Urol 165 1904–1907 Occurrence Handle1:CAS:528:DC%2BD3MXkt1CktLo%3D Occurrence Handle11371878
J Webber D Kessel D Fromm (1997) ArticleTitleSide effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res 68 31–37 Occurrence Handle10.1006/jsre.1997.5004 Occurrence Handle1:CAS:528:DyaK2sXivFantbk%3D Occurrence Handle9126192
L Wyld JL Burn MW Reed NJ Brown (1997) ArticleTitleFactors affecting aminolaevulinic acid-induced generation of protoporphyrin IX. Br J Cancer 76 705–712 Occurrence Handle1:CAS:528:DyaK2sXmsVantLc%3D Occurrence Handle9310234
Acknowledgments
We thank Stuart Marcus, MD, of DUSA Pharmaceuticals (Valhalla, NY, USA) for his support and for providing the ALA for this study. We are also grateful to T. J. Stephenson, MD, for assessment of the esophageal biopsy specimens. C.J.K. is funded by Yorkshire Cancer Research and the BUPA Foundation.
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Kelty, C., Ackroyd, R., Brown, N. et al. Comparison of high- vs low-dose 5-aminolevulinic acid for photodynamic therapy of Barrett’s esophagus . Surg Endosc 18, 452–458 (2004). https://doi.org/10.1007/s00464-003-9062-4
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DOI: https://doi.org/10.1007/s00464-003-9062-4