Skip to main content
SpringerLink
Log in

How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of high-grade dysplasia in Barrett’s esophagus

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is a novel treatment for high-grade dysplasia (HGD) in Barrett’s esophagus (BE). Our aim was to evaluate the effectiveness of differing light doses. Patients with HGD in BE received oral ALA (60 mg/kg) activated by low (500 J/cm), medium (750 J/cm), high (1,000 J/cm), or highest (1,000 J/cm ×2) light dose at 635 nm. Follow-up was by regular endoscopy with quadrantic biopsies. Twenty-four patients were treated. Successful eradication of HGD was significantly correlated with light dose (log rank, p < 0.01). Six of eight patients (75%) treated with the highest light dose, one of two treated with high dose (50%), two of nine (22%) receiving medium light dose, and zero of five receiving low light dose had successful eradication of HGD (median follow-up 45 months, range 1–78 months). No skin photosensitivity or esophageal strictures occurred. The efficacy of ALA-PDT for eradication of HGD in BE is closely related to the light dose used. With a drug dose of 60 mg/kg and light at 635 nm, we recommend a minimum light dose of 1,000 J/cm of esophagus. This dose appears safe.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hansen S, Wiig JN, Giercksky KE et al (1997) Esophageal and gastric carcinoma in Norway 1958–1992: incidence time trend variability according to morphological subtypes and organ subsites. Int J Cancer 71(3):340–344

    Article  PubMed  CAS  Google Scholar 

  2. Cameron AJ, Ott BJ, Payne WS (1985) The incidence of adenocarcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med 313(14):857–859

    Article  PubMed  CAS  Google Scholar 

  3. Cameron AJ, Carpenter HA (1997) Barrett’s esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study. Am J Gastroenterol 92(4):586–591

    PubMed  CAS  Google Scholar 

  4. Hirota WK, Loughney TM, Lazas DJ et al (1999) Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: prevalence and clinical data. Gastroenterology 116(2):277–285

    Article  PubMed  CAS  Google Scholar 

  5. Montgomery E, Goldblum JR, Greenson JK et al (2001) Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol 32(4):379–388

    Article  PubMed  CAS  Google Scholar 

  6. Reid BJ, Levine DS, Longton G et al (2000) Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 95(7):1669–1676

    PubMed  CAS  Google Scholar 

  7. Schnell TG, Sontag SJ, Chejfec G et al (2001) Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia. Gastroenterology 120(7):1607–1619

    Article  PubMed  CAS  Google Scholar 

  8. Heitmiller RF (2003) Prophylactic esophagectomy in Barrett esophagus with high-grade dysplasia. Langenbecks Arch Surg 388(2):83–87

    PubMed  Google Scholar 

  9. Tseng EE, Wu TT, Yeo CJ et al (2003) Barrett’s esophagus with high grade dysplasia: surgical results and long-term outcome—an update. J Gastrointest Surg 7(2):164–170

    Article  PubMed  Google Scholar 

  10. Swisher SG, Deford L, Merriman KW et al (2000) Effect of operative volume on morbidity, mortality, and hospital use after esophagectomy for cancer. J Thorac Cardiovasc Surg 119(6):1126–1132

    Article  PubMed  CAS  Google Scholar 

  11. Alexiou C, Beggs D, Salama FD et al (1998) Surgery for esophageal cancer in elderly patients: the view from Nottingham. J Thorac Cardiovasc Surg 116(4):545–553

    Article  PubMed  CAS  Google Scholar 

  12. Attwood SE, Lewis CJ, Caplin S et al (2003) Argon beam plasma coagulation as therapy for high-grade dysplasia in Barrett’s esophagus. Clin Gastroenterol Hepatol 1(4):258–263

    Article  PubMed  Google Scholar 

  13. Morris CD, Byrne JP, Armstrong GR et al (2001) Prevention of the neoplastic progression of Barrett’s oesophagus by endoscopic argon beam plasma ablation. Br J Surg 88(10):1357–1362

    Article  PubMed  CAS  Google Scholar 

  14. Ell C, May A, Gossner L et al (2000) Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett’s esophagus. Gastroenterology 118(4):670–677

    Article  PubMed  CAS  Google Scholar 

  15. Satodate H, Inoue H, Fukami N et al (2004) Squamous reepithelialization after circumferential endoscopic mucosal resection of superficial carcinoma arising in Barrett’s esophagus. Endoscopy 36(10):909–912

    Article  PubMed  CAS  Google Scholar 

  16. Barr H, Tralau CJ, Boulos PB et al (1987) The contrasting mechanisms of colonic collagen damage between photodynamic therapy and thermal-injury. Photochem Photobiol 46(5):795–800

    Article  PubMed  CAS  Google Scholar 

  17. Shaheen NJ, Inadomi JM, Overholt BF et al (2004) What is the best management strategy for high grade dysplasia in Barrett’s oesophagus? A cost effectiveness analysis. Gut 53(12):1736–1744

    Article  PubMed  CAS  Google Scholar 

  18. Vij R, Triadafilopoulos G, Owens DK et al (2004) Cost-effectiveness of photodynamic therapy for high-grade dysplasia in Barrett’s esophagus. Gastrointest Endosc 60(5):739–756

    Article  PubMed  Google Scholar 

  19. Overholt BF, Lightdale CJ, Wang KK et al (2005) Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett’s esophagus: international, partially blinded, randomized phase III trial. Gastrointest Endosc 62(4):488–498

    Article  PubMed  Google Scholar 

  20. Van Laethem JL, Peny MO, Salmon I et al (2000) Intramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett’s oesophagus. Gut 46(4):574–577

    Article  PubMed  Google Scholar 

  21. Overholt BF, Panjehpour M, Halberg DL (2003) Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: long-term results. Gastrointest Endosc 58(2):183–188

    Article  PubMed  Google Scholar 

  22. Shand A, Dallal H, Palmer K et al (2001) Adenocarcinoma arising in columnar lined oesophagus following treatment with argon plasma coagulation. Gut 48(4):580–581

    Article  PubMed  CAS  Google Scholar 

  23. Regula J, MacRobert AJ, Gorchein A et al (1995) Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX—a pilot study. Gut 36(1):67–75

    Article  PubMed  CAS  Google Scholar 

  24. Kelty CJ, Ackroyd R, Brown NJ et al (2004) Comparison of high- vs low-dose 5-aminolevulinic acid for photodynamic therapy of Barrett’s esophagus. Surg Endosc 18(3):452–458

    Article  PubMed  CAS  Google Scholar 

  25. Pech O, Gossner L, May A et al (2005) Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett’s cancer and high-grade intraepithelial neoplasia. Gastrointest Endosc 62(1):24–30

    Article  PubMed  Google Scholar 

  26. Gossner L, Stolte M, Sroka R et al (1998) Photodynamic ablation of high-grade dysplasia and early cancer in Barrett’s esophagus by means of 5-aminolevulinic acid. Gastroenterology 114(3):448–455

    Article  PubMed  CAS  Google Scholar 

  27. Ackroyd R, Kelty CJ, Brown NJ et al (2003) Eradication of dysplastic Barrett’s oesophagus using photodynamic therapy: long-term follow-up. Endoscopy 35(6):496–501

    Article  PubMed  CAS  Google Scholar 

  28. Kelty CJ, Ackroyd R, Brown NJ et al (2004) Endoscopic ablation of Barrett’s oesophagus: a randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation. Aliment Pharmacol Ther 20(11–12):1289–1296

    Article  PubMed  CAS  Google Scholar 

  29. Barr H, Shepherd NA, Dix A et al (1996) Eradication of high-grade dysplasia in columnar-lined (Barrett’s) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX. Lancet 348(9027):584–585

    Article  PubMed  CAS  Google Scholar 

  30. Peters F, Kara M, Rosmolen W et al (2005) Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in Barrett esophagus after endoscopic resection. Endoscopy 37(5):418–424

    Article  PubMed  CAS  Google Scholar 

  31. Ackroyd R, Brown NJ, Davis MF et al (2000) Photodynamic therapy for dysplastic Barrett’s oesophagus: a prospective, double blind, randomised, placebo controlled trial. Gut 47(5):612–617

    Article  PubMed  CAS  Google Scholar 

  32. Hage M, Siersema PD, van Dekken H et al (2004) 5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett’s oesophagus: a randomised trial. Gut 53(6):785–790

    Article  PubMed  CAS  Google Scholar 

  33. Forcione DG, Hasan T, Ortel BJ et al (2004) Optimization of aminolevulinic acid-based photodynamic therapy of Barrett’s esophagus with high grade dysplasia. Gastrointest Endosc 59(5):AB251

    Article  Google Scholar 

  34. Panjehpour M, Overholt BF, Phan MN et al (2005) Optimization of light dosimetry for photodynamic therapy of Barrett’s esophagus: efficacy vs. incidence of stricture after treatment. Gastrointest Endosc 61(1):13–18

    Article  PubMed  Google Scholar 

  35. Schlemper RJ, Riddell RH, Kato Y et al (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47(2):251–255

    Article  PubMed  CAS  Google Scholar 

  36. Lovat LB, Jamieson NF, Novelli MR et al (2005) Photodynamic therapy with m-tetrahydroxyphenyl chlorin for high-grade dysplasia and early cancer in Barrett’s columnar lined esophagus. Gastrointest Endosc 62(4):617–623

    Article  PubMed  Google Scholar 

  37. van Veen RL, Aalders MC, Pasma KL et al (2002) In situ light dosimetry during photodynamic therapy of Barrett’s esophagus with 5-aminolevulinic acid. Lasers Surg Med 31(5):299–304

    Article  PubMed  Google Scholar 

  38. Stringer MR, Kelty CJ, Ackroyd, R, Brown SB (2006) Light dosimetry measurements during ALA-PDT of Barrett’s oesophagus. Photodiag Photodynam Ther 3:19–26

    Article  Google Scholar 

  39. Tsutsui H, MacRobert AJ, Curnow A et al (2002) Optimisation of illumination for photodynamic therapy with mTHPC on normal colon and a transplantable tumour in rats. Lasers Med Sci 17(2):101–109

    Article  PubMed  CAS  Google Scholar 

  40. Curnow A, McIlroy BW, Postle-Hacon MJ et al (1999) Light dose fractionation to enhance photodynamic therapy using 5-aminolevulinic acid in the normal rat colon. Photochem Photobiol 69(1):71–76

    Article  PubMed  CAS  Google Scholar 

  41. Haringsma J, Siersema PD, Kuipers EJ (2004) Endoscopic ablation of Barrett’s neoplasia. Rotterdam results. Gastrointest Endosc 59(5):AB252

    Article  Google Scholar 

  42. van Hillegersberg R, Haringsma J, ten Kate FJW et al (2003) Invasive carcinoma after endoscopic ablative therapy for high-grade dysplasia in Barrett’s oesophagus. Dig Surg 20(5):440–444

    Article  PubMed  Google Scholar 

  43. Basu KK, Pick B, Bale R et al (2002) Efficacy and one year follow up of argon plasma coagulation therapy for ablation of Barrett’s oesophagus: factors determining persistence and recurrence of Barrett’s epithelium. Gut 51(6):776–780

    Article  PubMed  CAS  Google Scholar 

  44. Ban S, Mino M, Nishioka NS et al (2004) Histopathologic aspects of photodynamic therapy for dysplasia and early adenocarcinoma arising in Barrett’s esophagus. Am J Surg Pathol 28(11):1466–1473

    Article  PubMed  Google Scholar 

  45. Ackroyd R, Tam W, Schoeman M et al (2004) Prospective randomized controlled trial of argon plasma coagulation ablation vs. endoscopic surveillance of patients with Barrett’s esophagus after antireflux surgery. Gastrointest Endosc 59(1):1–7

    Article  PubMed  Google Scholar 

  46. Hornick JL, Blount PL, Sanchez CA et al (2005) Biologic properties of columnar epithelium underneath reepithelialized squamous mucosa in Barrett’s esophagus. Am J Surg Pathol 29(3):372–380

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the Association for International Cancer Research for supporting Dr. Jamieson to perform this project. DUSA pharmaceuticals kindly provided the drug and lasers for the study.

Author information

Authors and Affiliations

  1. National Medical Laser Centre, Department of Surgery, Royal Free and University College Medical School, University College London, 67-73 Riding House Street, London, W1W 7EJ, UK

    Gary D. Mackenzie, Neil F. Jamieson, C. Alexander Mosse, Benjamin R. Clark, Sally M. Thorpe, Stephen G. Bown & Laurence B. Lovat

  2. Department of Histopathology, Royal Free and University College Medical School, University College London, London, UK

    Marco R. Novelli

  3. Department of Gastroenterology, University College London Hospitals NHS Trust, London, UK

    Laurence B. Lovat

Authors
  1. Gary D. Mackenzie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neil F. Jamieson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco R. Novelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Alexander Mosse
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Benjamin R. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sally M. Thorpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephen G. Bown
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Laurence B. Lovat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laurence B. Lovat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mackenzie, G.D., Jamieson, N.F., Novelli, M.R. et al. How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of high-grade dysplasia in Barrett’s esophagus. Lasers Med Sci 23, 203–210 (2008). https://doi.org/10.1007/s10103-007-0473-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10103-007-0473-7

Keywords

Search

Navigation