Ying-Shiung Kuo

Diagnosis of oral cancer by light-induced autofluorescence spectroscopy using double excitation wavelengths

A cancer diagnostic algorithm, light-induced autofluorescence spectroscopy using double excitations wavelengths, was employed for distinguishing between cancerous and normal oral mucosa. For emission spectra at the shorter excitation wavelengths (280, 290, and 300 nm), the ratio between the area under 325-335 nm and the area under 465-475 nm was calculated. In the same way, for emission spectra at the longer excitation wavelengths (320, 330, and 340 nm), the ratio between the area under 375-385 nm and the area under 465-475 nm was calculated. Receiver operating characteristic curves were used to evaluate the performance of algorithms using single and the double (by combining shorter and longer) excitation wavelengths. The results showed that better performance, up to sensitivity 81.25%, specificity 93.75%, and positive predictive value 92.86%, could be achieved by using the double excitation wavelengths. The present study can be useful as a basis for further investigation on in vivo autofluorescence measurement and analysis using double excitation wavelength.

Association between Genetic Polymorphism of Tumor Necrosis Factor-a and Risk of Oral Submucous Fibrosis, a Pre-cancerous Condition of Oral Cancer

Many cytokines have been thought to play important roles in the pathogenesis of oral submucous fibrosis (OSF), an areca nut chewing-specific pre-cancerous condition characterized by the deposition of collagen in oral submucosa. Tumor necrosis factor-a (TNF-a), situated in the class III region of human leukocyte antigen (HLA), is a mediator with multiple functions, including the regulation of inflammatory reaction and transcriptions of collagen and collagenase. In total, 809 male subjects were recruited for assessment of the association of OSF with a bi-allelic promoter-region (-308) polymorphism on the TNFA gene. The high production allele, TNF2, was significantly lower among OSF subjects (n = 166) than in areca-chewing controls (n = 284). This association was independent of oral cancer status. The multivariate-adjusted odds ratio for the TNFA 11 genotype was 2.6 (95% confidence interval = 1.4-4.9 ; p = 0.004). The finding may imply a multifunctional etiological factor of TNF-α in OSF pathogenesis.

Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities

Betel quid (BQ) chewing is associated with an increased risk of oral submucous fibrosis (OSF) and oral cancer in India and many south-east Asian countries. Recently, we have shown that arecoline is cytotoxic to cultured human oral mucosal fibroblasts. This study investigated protective effects of various agents against the cytotoxicity of arecoline and its mechanisms. Arecoline, at concentrations of 0.2 and 0.4 mM, decreased the cell numbers by 38% and 63%, respectively. At a concentration of 2 mM, N-acetyl-L-cysteine [a glutathione (GSH) synthesis precursor] could prevent arecoline-induced cytotoxicity. The decrease in cell numbers was reduced to 17% relative to control. Extracellular addition of esterase at a concentration of 0.1 U/ml could almost completely protect the oral mucosal fibroblast (OMF) from arecoline-induced cytotoxicity. Arecoline is a muscarinic receptor agonist. However, atropine, a muscarinic receptor antagonist was unable to protect the cells from arecoline cytotoxicity at a concentration of 10 microM. Pretreatment of OMF with 50 microM buthionine sulfoximine (a cellular GSH synthesis inhibitor) or 0.5 mM diethylmaleate (a cellular GSH depleting agent) potentiated the cytotoxic effects of arecoline. These results indicate that cytotoxicity of arecoline on OMF is associated with cellular GSH levels and esterase activities. Factors that induce the GSH synthesis or esterase activity of oral mucosal cells can be used for future chemoprevention of BQ chewing-related lesions.

Oral verrucous hyperplasia: histologic classification, prognosis, and clinical implications

BACKGROUND Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. METHODS Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed. RESULTS We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 +/- 7 months. The mean time for malignant transformation was 22 +/- 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy. CONCLUSIONS We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Induction of the c-jun protooncogene expression by areca nut extract and arecoline on oral mucosal fibroblasts

To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in human oral mucosal fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increase was transient and the level of c-jun mRNAs returned rapidly to control levels thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at detectable levels. During AQ chewing, oral mucosal cells are continuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a minimal effect on arecoline-induced c-jun expression. Therefore, arecoline-induced c-jun expression is independent of GSH depletion.

Comparison of the Gow-Gates Mandibular Block and Inferior Alveolar Nerve Block Using a Standardized Protocol

BACKGROUND Although several previous studies have compared the efficacy of Gow-Gates mandibular block (GGMB) and inferior alveolar nerve block (IANB), the results remain controversial. This study used an objective, standardized and precise protocol to evaluate and compare the effectiveness and success rate of GGMB and IANB. METHODS The study group consisted of 162 patients (93 males and 69 females) who were randomly allocated to receive GGMB or IANB for extraction of third molars. Both methods used 2.7 mL of 2% xylocaine for each patient. Pulpal and gingival tissue anesthesia of mandibular central incisors, canines, first premolars and first molars were evaluated at 0, 5, 10, 15 and 60 minutes after injection of local anesthetic solution using both an electric pulp tester and a sharp explorer. RESULTS The success rates of pulpal anesthesia in the IANB group (central incisor, 6%; canine, 37%; first premolar, 54%; first molar, 88%) were not significantly different from the GGMB group (central incisor, 8.1%; canine, 37.1%; first premolar, 54.8%; first molar, 83.9%). All subjects achieved 100% lip numbness with both methods. At 60 minutes after injection, the success rates of gingival tissue anesthesia in canine buccal and lingual areas were higher in the IANB group (100% and 100%, respectively) than in the GGMB group (91.9% and 93.5%, respectively). In the molar buccal area, the success rates at 5 and 60 minutes after injection were higher in the IANB group (97% and 100%, respectively) than in the GGMB group (88.7% and 91.9%, respectively). Furthermore, the success rates in the molar lingual area at 10, 15 and 60 minutes after injection were higher in the IANB group (100%, 100% and 100%, respectively) than in the GGMB group (91.9%, 93.5% and 91.9%, respectively). Although IANB achieved higher success rates of gingival tissue anesthesia in some gingival areas, no significant difference between the two methods was found in overall efficacy. CONCLUSION This study demonstrated that the efficacy of pulpal and gingival tissue anesthesia are not significantly different between the GGMB and IANB methods.

Odontogenic Fibroma: A Clinicopathological Study of 15 Cases

BACKGROUND/PURPOSE Odontogenic fibroma (ODF) is a rare odontogenic tumor. It can be further divided into peripheral odontogenic fibroma (PODF) and central odontogenic fibroma (CODF). This retrospective study evaluated the clinical and histopathological features of 15 ODFs in Taiwanese patients. METHODS Fifteen consecutive cases of ODF were collected from 1984 to 2009. The clinical data and microscopic features of these cases were reviewed and analyzed. RESULTS Twelve PODFs were excised from six male and six female patients (mean age: 35 years) and three CODFs from two male and one female patients (mean age: 11 years). Eight of the 12 PODFs were found on the mandibular gingiva and four on the maxillary gingiva, with the most common site being the mandibular anterior and premolar region (5 cases). Two CODFs were located in the molar region of the mandible and one in the anterior maxilla. Two CODFs showed a mixed lesion and one a radiolucent lesion. No recurrence of the 15 ODFs was found after total excision or enucleation. Microscopically 58.3% of the PODFs showed surface ulcèration. Calcified foci composed of osteoid, cementoid, or cementicle-like materials were noted in all 15 ODFs. Nests or strands of odontogenic epithelium were found in all 15 ODFs. The stromal component was mainly fibro-collagenous in nine of the 12 PODFs, whereas two of the three CODFs contained predominantly myxomatous stroma. CONCLUSION PODFs occurred more commonly than CODFs. PODF showed an equal sex distribution and was found more frequently in patients in the third to fourth decades of life. The most commonly affected site was the mandibular gingiva, especially the anterior and premolar gingiva. Only three CODFs were found; therefore, we could not draw any conclusions about CODF in Taiwanese patients.

Clinicopathological Study of Oral Giant Cell Fibromas

BACKGROUND/PURPOSE Oral giant cell fibromas (GCFs) are found predominantly in Caucasians and rarely in other races. This retrospective study evaluated the clinicopathological features of 24 GCFs in Taiwanese patients. METHODS Twenty-four consecutive cases of oral GCF were investigated from 1987 to 2008. Clinical data and microscopic features were reviewed and analyzed. RESULTS The mean age of patients at the time of diagnosis was 29 years. Oral GCF occurred more commonly in patients between 11 and 40 years of age. There were 12 male and 12 female patients. The lesions were found more frequently on the tongue (8 cases) and gingiva (7 cases). The mean size of the lesion was 5.5mm (range, 2-10 mm) in greatest dimension. GCF is misdiagnosed frequently as fibroma (19 cases) or papilloma (5 cases). All tumors were treated by total surgical excision and no recurrence was found after treatment. Microscopically, the GCF was a sessile or pedunculated mass covered with a thin layer of parakeratinized or orthokeratinized stratified squamous epithelium. The tumor was composed mainly of loose or dense fibrous connective tissue with well-formed capillaries and no inflammation. The consistent and diagnostic feature was the presence of large stellate giant cells, usually with one or two nuclei. Multinucleated giant cells were seen occasionally. These giant cells were most numerous in the connective tissue just beneath the epithelium. CONCLUSION Oral GCFs show no significant sex predilection and occur in patients in the second to fourth decades of life. Usually, the lesions are < 1 cm in diameter and are found more frequently on the tongue and gingiva. GCF resembles fibroma or papilloma and is difficult to diagnose correctly at the first glance. All GCFs can be treated by conservative surgical excision without subsequent recurrence.

Clinicopathological Study of 252 Jaw Bone Periapical Lesions From a Private Pathology Laboratory

BACKGROUND/PURPOSE Periapical lesions are common sequelae of pulp diseases. This retrospective study evaluated the clinical and histopathological features of periapical lesions sent to a private pathology laboratory by dentists in private clinics. METHODS Two hundred and fifty-two consecutive cases of periapical lesions were collected from September 2005 to October 2009. Clinical data and histopathological features of these periapical lesions were reviewed and analyzed. RESULTS The 252 periapical lesions consisted of 128 periapical granulomas, 117 periapical cysts, and seven periapical scars. These 252 lesions were taken from 252 patients (92 men and 160 women; mean age = 43.6 years; range, 9-81 years). Of the 252 periapical lesions, 186 were found in the maxilla and 66 in the mandible. The most common site for periapical lesions was the maxillary anterior region (134 cases, including 73 granulomas, 54 cysts and 7 scars), and the most frequently involved tooth was the maxillary lateral incisor (64 cases, including 29 granulomas, 31 cysts and 4 scars). Of the 117 periapical cysts, 116 were lined by stratified squamous epithelium and one by mucoepidermoid epithelium. Hyaline bodies were discovered in the lining epithelium of four periapical cysts. Odontogenic epithelial rest, cholesterol cleft, foamy histiocytes, hemosiderin-laden macrophages, dystrophic calcification, foreign bodies, and bacterial clumps were found in five, three, nine, two, 28, 10 and one periapical granulomas, respectively, as well as in six, 11, eight, seven, 19, nine and eight periapical cysts, respectively. CONCLUSION Granulomas and cysts were the two most common periapical lesions. Periapical lesions occurred more frequently in female patients and in those in their fourth to fifth decades. The most commonly affected site for periapical lesions was the maxillary anterior region, and the most frequently involved tooth was the maxillary lateral incisor.

Successful treatment of an early invasive oral squamous cell carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy

Our previous studies showed successful treatment of a series of 36 oral verrucous hyperplasia lesions and of an extensive oral verrucous carcinoma with a topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (topical ALA-PDT) protocol (with a fluence rate of 100 mW/cm 2 and a light exposure dose of 100 J/cm 2 ) using a 635-nm light-emitting diode (LED) light source. In this case report, we tested whether an enhanced topical ALA-PDT protocol (with a fluence rate of 200 mW/cm 2 and a light exposure dose of 200 J/cm 2 ) could be used to treat an early invasive oral squamous cell carcinoma (OSCC) with a verrucous appearance of the left lower posterior edentulous alveolar mucosa of a 67-year-old male former areca-quid chewer and ex-smoker. The main verrucous lesion showed complete regression after eight treatments with PDT. However, 10 extra treatments were needed to eradicate the multiple residual leukoplakia lesions on the edentulous alveolar mucosa. Moderate to severe post-PDT pain was noted during the initial eight treatments, and the patient needed analgesics (codeine phosphate, 30 mg three times daily) to control the pain. No recurrence of the OSCC lesion was found after a follow-up period of 4 years. We suggest that our enhanced topical ALA-PDT protocol may have good potential to be used as a treatment of choice for a superficially invasive OSCC without regional or distant metastasis before the commencement of other effective therapies.