Poor Results of 5-Aminolevulinic Acid-Photodynamic Therapy for Residual High-Grade Dysplasia and Early Cancer in Barrett Esophagus after Endoscopic Resection

 

 Buy Article Permissions and Reprints

Background and Study Aims: The aim of the study was to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or early cancer (HGD/EC) after endoscopic resection in Barrett esophagus.
Patients and Methods: Study patients were separated into group A, with proven residual HGD/EC, and group B with possible HGD/EC (positive lateral margins in the endoscopic resection specimen, without HGD/EC in the remaining Barrett esophagus). PDT treatment consisted of 5-aminolevulinic (5-ALA) photosensitization (40 mg/kg) followed by illumination of the Barrett esophagus with a total light dose of 100 J/cm². Complete remission was defined as the absence of HGD/EC in biopsies taken in two consecutive follow-up endoscopies. The percentage regression of Barrett esophagus, as well as the recurrence rate of HGD/EC, was calculated.

Results: 20 patients underwent PDT (group A, 11; group B, 9). Mild complications were seen in 4/26 procedures. The overall success rate was 15/20 (75 %). There was a significant difference in success rate between group A (55 %) and group B (100 %); P = 0.03. All patients had residual Barrett esophagus after PDT; the median regression percentage was 50 % (IQR 25 - 70 %). Recurrence of HGD/EC occurred in four patients (two each in groups A and B) after a median follow up of 30 months.

Conclusions: In this selected group of patients, the addition of 5-ALA-PDT after endoscopic resection for HGD/EC had a disappointing success rate in patients who had residual HGD/EC after endoscopic resection. Most patients undergoing 5-ALA-PDT have residual Barrett mucosa after PDT and 5-ALA-PDT does not seem to prevent recurrences during follow-up.

References

• 1 Cameron A J. Epidemiology of columnar-lined esophagus and adenocarcinoma.  Gastroenterol Clin N Am. 1997;  26 487-494
  CrossrefPubMedGoogle Scholar
• 2 O’Connor J B, Falk G W, Richter J E. The incidence of adenocarcinoma and dysplasia in Barrett’s esophagus: report on the Cleveland Clinic Barrett’s Esophagus Registry.  Am J Gastroenterol. 1999;  94 2037-2042
  PubMedGoogle Scholar
• 3 Birkmeyer J D, Siewers A E, Finlayson E V. et al . Hospital volume and surgical mortality in the United States.  N Engl J Med. 2002;  346 1128-1137
  CrossrefPubMedGoogle Scholar
• 4 Bonavina L. Early oesophageal cancer: results of a European multicentre survey. Group Europeen pour l’Étude des Maladies de l’Oesophage.  Br J Surg. 1995;  82 98-101
  PubMedGoogle Scholar
• 5 Heitmiller R F, Redmond M, Hamilton S R. Barrett’s esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy.  Ann Surg. 1996;  224 66-71
  CrossrefPubMedGoogle Scholar
• 6 Holscher A H, Bollschweiler E, Schneider P M, Siewert J R. Early adenocarcinoma in Barrett’s oesophagus.  Br J Surg. 1997;  84 1470-1473
  CrossrefPubMedGoogle Scholar
• 7 Nigro J J, Hagen J A, DeMeester T R. et al . Occult esophageal adenocarcinoma: extent of disease and implications for effective therapy.  Ann Surg. 1999;  230 433-438
  CrossrefPubMedGoogle Scholar
• 8 Rice T W, Falk G W, Achkar E, Petras R E. Surgical management of high-grade dysplasia in Barrett’s esophagus.  Am J Gastroenterol. 1993;  88 1832-1836
  PubMedGoogle Scholar
• 9 Thomas P, Doddoli C, Neville P. et al . Esophageal cancer resection in the elderly.  Eur J Cardiothorac Surg. 1996;  10 941-946
  CrossrefPubMedGoogle Scholar
• 10 Buttar N S, Wang K K, Lutzke L S. et al . Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett’s esophagus.  Gastrointest Endosc. 2001;  54 682-688
  PubMedGoogle Scholar
• 11 May A, Gossner L, Pech O, Fritz A. et al . Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett’s oesophagus: acute-phase and intermediate results of a new treatment approach.  Eur J Gastroenterol Hepatol. 2002;  14 1085-1091
  CrossrefPubMedGoogle Scholar
• 12 Bergman J JGHM, Fockens P, Van Lanschot J J. et al . Endoscopic mucosal resection (EMR) for intramucosal neoplasia in Barrett’s esophagus [abstract].  Gastrointest Endosc. 2002;  55 AB206
  PubMedGoogle Scholar
• 13 Peters F P, Kara M A, Rosmolen W D. et al . Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett esophagus.  Gastrointest Endosc. 2005;  61 506-514
  CrossrefPubMedGoogle Scholar
• 14 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
  CrossrefPubMedGoogle Scholar
• 15 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.  Gastroenterology. 1998;  114 448-455
  PubMedGoogle Scholar
• 16 Haringsma J, Siersema P D, Kuipers E J. Endoscopic ablation of Barrett’s neoplasia. Rotterdam results [abstract].  Gastrointest Endosc. 2004;  59 AB252
  PubMedGoogle Scholar
• 17 Macrae F A, Rajesekaram R, Thomas R, Bhathal P S. Photodynamic therapy in high grade dysplasia in Barrett’s oesophagus using 5 amino-levulinic acid sensitization [abstract].  Gastrointest Endosc. 2004;  59 AB252
  PubMedGoogle Scholar
• 18 Pech O, Gossner L, May A. et al . Long term results of PDT for early neoplasia in Barrett’s esophagus [abstract].  Gastrointest Endosc. 2004;  59 AB257
  PubMedGoogle Scholar
• 19 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
  CrossrefPubMedGoogle Scholar
• 20 Ackroyd R, Kelty C J, Brown N J. et al . Eradication of dysplastic Barrett’s oesophagus using photodynamic therapy: long-term follow-up.  Endoscopy. 2003;  35 496-501
  Article in Thieme ConnectPubMedGoogle Scholar
• 21 Kelty C J, Ackroyd R, Brown N J. et al . Comparison of high- vs. low-dose 5-aminolevulinic acid for photodynamic therapy of Barrett’s esophagus.  Surg Endosc. 2004;  18 452-458
  CrossrefPubMedGoogle Scholar
• 22 Forcione D G, Hasan T, Ortel B J, Nishioka N S. Optimization of aminolevulinic acid-based photodynamic therapy of Barrett’s esophagus with high grade dysplasia [abstract].  Gastrointest Endosc. 2004;  59 AB251
  PubMedGoogle Scholar
• 23 Kelty C, Ackroyd R, Brown N J. et al . Endoscopic ablation of Barrett’s esophagus: a randomized trial of photodynamic therapy (PDT) versus argon plasma coagulation (APC) [abstract].  Gastrointest Endosc. 2004;  59 AB250
  PubMedGoogle Scholar
• 24 Selvasekar C R, Novelli M R, Thorpe S M. et al . Interim results of a randomized controlled trial (RCT) comparing green and red laser photodynamic therapy using low dose ALA for high grade dysplasia [abstract].  Gastrointest Endosc. 2004;  59 AB252
  PubMedGoogle Scholar
• 25 van den Boogert B J, van Hillegersberg R, de Rooij F W. et al . 5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration.  J Photochem Photobiol B. 1998;  44 29-38
  CrossrefPubMedGoogle Scholar
• 26 van den Boogert B J, van Hillegersberg R, van Staveren H J. et al . Timing of illumination is essential for effective and safe photodynamic therapy: a study in the normal rat oesophagus.  Br J Cancer. 1999;  79 825-830
  CrossrefPubMedGoogle Scholar
• 27 Hage M, Siersema P D, van Dekken H. et al . 5-Aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett’s oesophagus: a randomised trial.  Gut. 2004;  53 785-790
  CrossrefPubMedGoogle Scholar
• 28 Tan W C, Fulljames C, Stone N. et al . Photodynamic therapy using 5-aminolaevulinic acid for oesophageal adenocarcinoma associated with Barrett’s metaplasia.  J Photochem Photobiol B. 1999;  53 75-80
  CrossrefPubMedGoogle Scholar
• 29 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
  CrossrefPubMedGoogle Scholar
• 30 Overholt B F, Panjehpour M, Halberg D L. Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: long-term results.  Gastrointest Endosc. 2003;  58 183-188
  CrossrefPubMedGoogle Scholar
• 31 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
  CrossrefPubMedGoogle Scholar
• 32 Hage M, van Dekken H, Vissers K J. et al . Molecular aberrations are still present after ablative therapy of Barrett’s esophagus [abstract].  Gastrointest Endosc. 2004;  59 AB249
  PubMedGoogle Scholar
• 33 Chen X, Ding Y W, Yang G, Bondoc F. et al . Oxidative damage in an esophageal adenocarcinoma model with rats.  Carcinogenesis. 2000;  21 257-263
  CrossrefPubMedGoogle Scholar
• 34 Farhadi A, Fields J, Banan A, Keshavarzian A. Reactive oxygen species: are they involved in the pathogenesis of GERD, Barrett’s esophagus, and the latter's progression toward esophageal cancer?.  Am J Gastroenterol. 2002;  97 22-26
  CrossrefPubMedGoogle Scholar
• 35 Olyaee M, Sontag S, Salman W. et al . Mucosal reactive oxygen species production in oesophagitis and Barrett’s oesophagus.  Gut. 1995;  37 168-173
  PubMedGoogle Scholar
• 36 Wetscher G J, Hinder R A, Klingler P. et al . Reflux esophagitis in humans is a free radical event.  Dis Esophagus. 1997;  10 29-32
  PubMedGoogle Scholar
• 37 Wang K K, Buttar N S, Wong Kee  . et al . Assessment of genetic defects in patients with complete versus partial ablation after photodynamic therapy (PDT) for Barrett’s esophagus [abstract].  Gastroenterology. 2004;  126(4 Suppl 2) A-177
  PubMedGoogle Scholar
• 38 Seewald S, Akaraviputh T, Seitz U. et al . Circumferential EMR and complete removal of Barrett’s epithelium: a new approach to management of Barrett’s esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma.  Gastrointest Endosc. 2003;  57 854-859
  CrossrefPubMedGoogle Scholar
• 39 Giovannini M, Bories E, Pesenti C. et al . Circumferential endoscopic mucosal resection in Barrett’s Esophagus with high-grade intraepithelial neoplasia or mucosal cancer: preliminary results in 21 patients.  Endoscopy. 2004;  36 782-787
  Article in Thieme ConnectPubMedGoogle Scholar
• 40 Nomura T, Boku N, Ohtsu A. et al . Recurrence after endoscopic mucosal resection for superficial esophageal cancer.  Endoscopy. 2000;  32 277-280
  Article in Thieme ConnectPubMedGoogle Scholar

J. J. G. H. M. Bergman, M. D. Ph. D.

Department of Gastroenterology and Hepatology, Academic Medical Center

Meibergdreef 9 · 1105 AZ, Amsterdam · The Netherlands

Email: j.j.bergman@amc.uva.nl