Initial experience in the treatment of oral leukoplakia with high-dose vitamin A and follow-up 5-aminolevulinic acid induced protoporphyrin IX fluorescence

Abstract The aim of photodynamic diagnostics is complete visualization of all neoplastic lesions in a tumorous organ after the application of a tumor-selective photosensitizer. We explored the potential benefit of a combination of retinyl palmitate for the treatment of oral leukoplakias and follow-up diagnosis of malignant tissue by using 5-aminolevulinic acid (5-ALA) as a fluorescence marker. Semiquantitative measurements were performed following the topical application of 5-ALA in six patients. After biopsy and histological evaluation of tissue specimens the patients were treated with escalating doses of retinyl palmitate. After treatment periods ranging from 4 to 8 weeks 5-ALA was again applied for photodetection of persisting fluorescence. In all cases prior to retinyl palmitate treatment a prominent red fluorescence indicated tissue dysplasia. Eight weeks after treatment with retinyl palmitate decreased red fluorescence intensities were found, and repeated histological evaluations showed no persistent signs of dysplastic lesions. Our initial experience shows that high doses of retinyl palmitate can be useful for treating dysplastic lesions in the upper aerodigestive tract and can be monitored with 5-ALA induced protoporphyrin IX fluorescence.

[1]  M. Strong,et al.  Field cancerization in the aerodigestive tract--its etiology, manifestation, and significance. , 1984, The Journal of otolaryngology.

[2]  B. Cheson,et al.  Retinoids in cancer therapy. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  J S Lee,et al.  Suppression of retinoic acid receptor-beta in premalignant oral lesions and its up-regulation by isotretinoin. , 1995, The New England journal of medicine.

[4]  S Silverman,et al.  Early diagnosis of oral cancer , 1988, Cancer.

[5]  B Palcic,et al.  Diagnostic imaging of the larynx: autofluorescence of laryngeal tumours using the helium-cadmium laser , 1995, The Journal of Laryngology & Otology.

[6]  W. Hong,et al.  13-cis-retinoic acid in the treatment of oral leukoplakia. , 1986, The New England journal of medicine.

[7]  K. D. Devine,et al.  Tetracycline‐Induced fluorescence of laryngeal, pharyngeal, and oral cancer , 1972, The Laryngoscope.

[8]  W. Issing,et al.  Long‐term follow‐up of larynx leukoplakia under treatment with retinyl palmitate , 1996, Head & neck.

[9]  S. Lippman,et al.  13-cis-retinoic acid and cancer chemoprevention. , 1992, Journal of the National Cancer Institute. Monographs.

[10]  J R Leonard,et al.  Hematoporphyrin fluorescence: An aid in diagnosis of malignant neoplasms , 1971, The Laryngoscope.

[11]  L. Rasetti,et al.  Porphyrin metabolism in human neoplastic tissues. , 1966, Panminerva medica.

[12]  L. Rasetti,et al.  [Ferrochelatase, ALA-dehydrase and ALA-synthetase activity in human tumor tissues]. , 1966, Minerva medica.

[13]  D. Gnepp,et al.  Epidemiology of carcinoma in situ of the upper. Aerodigestive tract , 1988, Cancer.

[14]  W. Bollag,et al.  Retinoids in cancer prevention and therapy. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  J C Kennedy,et al.  Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. , 1992, Journal of photochemistry and photobiology. B, Biology.

[16]  A E Profio,et al.  Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. , 1993, The Journal of thoracic and cardiovascular surgery.

[17]  R. van Hillegersberg,et al.  Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. , 1992, Gastroenterology.

[18]  A. Leunig,et al.  Detection of Squamous Cell Carcinoma of the Oral Cavity by Imaging 5‐Aminolevulinic Acid‐Induced Protoporphyrin IX Fluorescence , 2000, The Laryngoscope.

[19]  Herbert Stepp,et al.  Bladder tissue diagnostics utilizing Protoporphyrin IX fluorescence detection , 1995, Other Conferences.

[20]  Hitoshi Shibuya,et al.  Multiple primary cancer risk in patients with squamous cell carcinoma of the oral cavity , 1987 .

[21]  D. Alberts,et al.  13-Cis-retinoic acid: pharmacology, toxicology, and clinical applications for the prevention and treatment of human cancer. , 1985, Critical reviews in oncology/hematology.

[22]  W R Wilson,et al.  Toluidine blue staining of the esophagus. A useful adjunct in the panendoscopic evaluation of patients with squamous cell carcinoma of the head and neck. , 1987, Archives of otolaryngology--head & neck surgery.

[23]  G. Kuhnle,et al.  In vivo kinetics and spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster. , 1994, British Journal of Cancer.

[24]  C Scully,et al.  Toluidine blue and Lugol's iodine application in the assessment of oral malignant disease and lesions at risk of malignancy. , 1992, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[25]  J C Kennedy,et al.  Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized protoporphyrin IX fluorescence. , 1990, The American journal of pathology.

[26]  T. Tong,et al.  Cancer statistics, 1991. , 1991, Boletin de la Asociacion Medica de Puerto Rico.

[27]  N. Navone,et al.  Heme biosynthesis in human breast cancer--mimetic "in vitro" studies and some heme enzymic activity levels. , 1990, The International journal of biochemistry.

[28]  W. Issing,et al.  Expression of retinoic acid receptors in squamous cell carcinomas and their possible implication for chemoprevention. , 1996, Anticancer research.

[29]  K Svanberg,et al.  Photodynamic therapy of non‐melanoma malignant tumours of the skin using topical δ‐amino levulinic acid sensitization and laser irradiation , 1994, The British journal of dermatology.

[30]  H Stepp,et al.  Fluorescence imaging and spectroscopy of 5-aminolevulinic acid induced protoporphyrin IX for the detection of neoplastic lesions in the oral cavity. , 1996, American journal of surgery.

[31]  B. Palcic,et al.  Autofluorescence of normal and malignant bronchial tissue , 1991, Lasers in surgery and medicine.

[32]  H Stepp,et al.  Fluorescence staining of laryngeal neoplasms after topical application of 5‐aminolevulinic acid: Preliminary results , 1999, Lasers in surgery and medicine.