Fluorescence diagnosis aims to improve the management of oral cancer via early detection of the malignant lesions and better delimitation of the tumor margins. This paper presents a comparative study of normal inspection, combined fluorescence diagnosis (CFD) and its 2 main components, autofluorescence and 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence. Biopsy-controlled fluorescence imaging and spectral analysis were performed on a total of 85 patients with suspected or histologically proven oral carcinoma both before and after topical administration of 5-ALA (200 mg 5-ALA dissolved in 50 ml of H 2 0). Fluorescence excitation was accomplished using filtered light of a xenon short arc lamp ( ؍ 375-440 nm). As for CFD, a "streetlight" contrast (red to green) was readily found between malignant and healthy tissue on the acquired images. In terms of tumor localization and delimitation properties, CFD was clearly favorable over either normal inspection or its 2 components in fluorescence imaging. The performance of CFD was found to be impeded by tumor keratinization but to be independent of either tumor staging, grading or localization. In spectral analysis, cancerous tissue showed significantly higher PPIX fluorescence intensities and lower autofluorescence intensities than normal mucosa. There is a great potential for CFD in early detection of oral neoplasms and exact delimitation of the tumors' superficial margins and an advantage over white light inspection and each of its 2 main components. The method is noninvasive, safe and easily reproducible. © 2002 Wiley-Liss, Inc.
Key words: combined fluorescence diagnosis; autofluorescence photodetection; protoporphyrin IX; 5-aminolevulinic acid; oral cancer; spectroscopyMalignant neoplasms of the upper aerodigestive tract are of major importance in modern health care. Head and neck cancer is the fifth most common cancer worldwide. 1 In most industrialized countries, both morbidity and mortality rates of squamous cell carcinoma of the oral cavity or oropharynx show an upward tendency. A possible way to increase cure rates of oral cancer lies in early detection followed by radical surgery. 2 However, early lesions are often hard to detect and are sometimes overlooked, even by experienced clinicians. These early invasive carcinomas or carcinomas in situ might simply appear as flat, inconspicuous irregularities of the mucosal surface and may lack typical morphologic characteristics of malignant tumors. At the same time, especially when tongue-like, submucosal spreading of malignancy or diffuse infiltration into surrounding tissue layers is present, superficial demarcation of the tumor borders via simple inspection and/or other common diagnostic procedures often remains unsatisfactory. This may result in prolonged operation times or, in the worst case, might prevent a successful resection in terms of tumorfree borders, along with increased rates of local recurrence and a reduction in 5-year survivals. 3 To facilitate diagnosis of early or secon...