Chuan-Hang Yu

Chung Shan Medical University, 臺中市, Taiwan, Taiwan

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Publications (24)47.62 Total impact

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    ABSTRACT: Previous studies have used cryotherapy for the treatment of oral precancers including oral leukoplakia (OL) and oral verrucous hyperplasia (OVH) as well as oral cancers including oral verrucous carcinoma (OVC) and oral squamous cell carcinoma (OSCC). Cryotherapy is a method that locally destroys lesional tissues by freezing in situ. It can be carried out by either an “open” or a “closed” system. Lesional tissues are destroyed mainly through disruption of cell membrane, cellular dehydration, enzyme and protein damage, cell swelling and rupture, thermal shock injury to cells, damage to vasculature, and immune-mediated cytotoxicity. Cryotherapy is used frequently for the treatment of OL lesions with promising results. It can also be used to treat OVH and OVC lesions. Because OVH and OVC lesions are usually fungating and bulky, a combination therapy of shave excision and cryotherapy is needed to achieve a complete regression of the lesion. OSCCs have also been treated by cryotherapy. However, cryotherapy is not the main-stream treatment modality for OSCCs. Cryotherapy seems suitable for treatment of thin or relatively thick plaque-typed lesions such as OL lesions. By careful selection of patients, cryotherapy is a simple, safe, easy, conservative, and acceptable treatment modality for certain benign oral lesions and oral precancers.
    Journal of the Formosan Medical Association 01/2014; · 1.00 Impact Factor
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    ABSTRACT: Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) to treat oral precancers including oral leukoplakia (OL), oral erythroleukoplakia (OEL), and oral verrucous hyperplasia (OVH) as well as oral cancers including oral verrucous carcinoma (OVC) and oral squamous cell carcinoma (OSCC). Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2) was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2) on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for treatment of oral precancers and cancers. It is concluded that topical ALA-PDT using either light emitting diode or laser light is very effective for OVH and OEL lesions but is relatively less effective for OL lesions. If OVC or early-invasive OSCC has no concurrent regional or distant metastasis, regular or enhanced topical ALA-PDT may have a high potential to treat these two particular kinds of oral cancer. A large-scale human clinical trial is needed to evaluate the efficacies of drug-preconditioned topical ALA-PDT and chemotherapy or cryotherapy-combined topical ALA-PDT on oral precancers, OVC and early-invasive OSCC in the near future.
    Journal of Dental Sciences. 12/2012; 7(4):307–315.
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    ABSTRACT: BACKGROUND: Our previous studies showed that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is very effective for oral verrucous hyperplasia (OVH) and relatively less effective for oral leukoplakia (OL) lesions. Nevertheless, there has been no report on the association of the expression of apoptosis-related proteins in OVH and OL biopsy tissues prior to PDT with PDT treatment outcomes. METHODS: This study used immunohistochemistry to evaluate whether the expression of Bak, Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein in biopsy specimens of OVH and OL lesions could be used to predict the clinical outcomes of 18 OVH and 40 OL lesions treated with topical ALA-PDT. The marker labeling score (LS) was defined as labeling index (positive cells/total cells) multiplied by staining intensity. The lesions after ALA-PDT treatment were divided into complete response (CR) group and partial or no response (PR/NR) group. RESULTS: The mean Bak LS and the mean Bak/Mcl-1 LS ratio were significantly higher in the CR group than in the PR/NR group. However, there was no significant difference in the Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein LS between the CR and PR/NR groups. CONCLUSION: We conclude that the Bak LS or Bak/Mcl-1 LS ratio may be a useful biomarker to predict the clinical outcomes of OVH and OL lesions treated with topical ALA-PDT. Pre-PDT epithelial cell levels of Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, and PCNA may not have a significant influence on the clinical outcome of OVH and OL lesions treated with topical ALA-PDT.
    Journal of Oral Pathology and Medicine 09/2012; · 2.06 Impact Factor
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    ABSTRACT: Our previous study showed that cotton-swab cryotherapy is an alternative treatment modality for oral leukoplakia. This study used liquid nitrogen spray with a cryogun (cryogun cryotherapy) to treat 60 oral leukoplakia lesions. Complete regression was achieved in all 60 oral leukoplakia lesions after cryogun cryotherapy. We found that 60 oral leukoplakia lesions treated with cryogen cryotherapy needed significantly fewer mean treatments (3.1 ± 1.3) to achieve complete regression than 60 previously reported oral leukoplakia lesions treated with cotton-swab cryotherapy (mean, 6.3 ± 3.8 treatments). Oral leukoplakia lesions on oral mucosal sites other than the tongue, <2 cm(2) , with epithelial dysplasia, or with a surface keratin thickness <55 μm required significantly fewer cryogun cryotherapy treatments to achieve complete regression. For treatment of oral leukoplakia, the cryogun cryotherapy needed fewer mean treatments to achieve complete regression of the lesions than the cotton-swab cryotherapy.
    Head & Neck 11/2011; 34(9):1306-11. · 2.83 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Journal of the Formosan Medical Association 11/2010; 109(11):810-8. · 1.00 Impact Factor
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    ABSTRACT: Oral verrucous hyperplasia (OVH) and oral erythroleukoplakia (OEL) are two oral precancerous lesions with relatively high malignant transformation potential. One of the best cancer prevention strategies is to use a conservative and effective treatment modality to eliminate oral precancers to stop their further malignant transformation. Our previous studies have shown that the topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) using the 635-nm light-emitting diode (LED) light is very effective for OVH and OEL lesions. Because the laser machine is a more-popular light source than the LED device in PDT clinics, in this study 40 OVH and 40 OEL lesions were treated once a week with the same PDT protocol but using the 635-nm laser light to evaluate whether this laser light-mediated topical ALA-PDT was also effective for OVH and OEL lesions. We found that all the 40 OVH lesions exhibited complete response (CR) after an average of 3.6 PDT treatments. Of the 40 OEL lesions, 38 showed CR after an average of 3.4 PDT treatments and two showed partial response (PR). Better PDT outcomes were significantly associated with OVH and OEL lesions with the smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. This study indicates that the laser light-mediated topical ALA-PDT is also very effective for OVH and OEL lesions. Therefore, we suggest that topical ALA-PDT using either the LED or laser light may serve as the first-line treatment of choice for OVH and OEL lesions.
    Journal of Oral Pathology and Medicine 09/2010; 39(8):624-30. · 2.06 Impact Factor
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    ABSTRACT: Pituitary tumor transforming gene (PTTG1, securin) is involved in cell-cycle control through inhibition of sister-chromatid separation. Elevated levels of PTTG1 were found to be associated with many different tumor types that might be involved in late stage tumor progression. However, the role of PTTG1 in early stage of tumorigenesis is unclear. Here we utilized the adenovirus expression system to deliver PTTG1 into normal human fibroblasts to evaluate the role of PTTG1 in tumorigenesis. Expressing PTTG1 in normal human fibroblasts inhibited cell proliferation. Several senescence-associated (SA) phenotypes including increased SA-beta-galactosidase activities, decreased bromodeoxyuridine incorporation, and increased SA-heterochromatin foci formation were also observed in PTTG1-expressing cells, indicating that PTTG1 overexpression induced a senescent phenotype in normal cells. Significantly, the PTTG1-induced senescence is p53-dependent and telomerase-independent, which is distinctively different from that of replicative senescence. The mechanism of PTTG1-induced senescence was also analyzed. Consistent with its role in regulating sister-chromatid separation, overexpression of PTTG1 inhibited the activation of separase. Consequently, the numbers of cells with abnormal nuclei morphologies and chromosome separations were increased, which resulted in activation of the DNA damage response. Thus, we concluded that PTTG1 overexpression in normal human fibroblasts caused chromosome instability, which subsequently induced p53-dependent senescence through activation of DNA-damage response pathway.
    Journal of Biological Chemistry 05/2010; 285(29):22630-8. · 4.65 Impact Factor
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    ABSTRACT: 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/cm2 and a light exposure dose of 100 J/cm2) 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/cm2 and a light exposure dose of 200 J/cm2) 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.
    Journal of Dental Sciences - J DENT SCI. 01/2010; 5(1):36-40.
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    ABSTRACT: Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) using a 635-nm light-emitting diode (LED) light is an effective treatment modality for oral verrucous hyperplasia. This study tested whether topical ALA-PDT using either the LED or laser light was also an effective treatment modality for oral erythroleukoplakia (OEL) lesions. In this prospective but non-randomized study, 20 OEL lesions were treated with topical ALA-PDT using the 635-nm LED light and 26 OEL lesions were treated with topical ALA-PDT using the 635-nm laser light. The difference in clinical outcomes was compared between the two groups by Fisher exact test. We found that the 20 LED light-treated OEL lesions showed complete response (CR) in 17 and partial response (PR) in 3. The 17 CR OEL lesions required an average of 3.7 (range, 2-7) treatments of ALA-PDT to achieve CR of the lesions. The 26 laser light-treated OEL lesions showed CR in 25 and PR in 1. The 25 CR OEL lesions needed an average of 3.3 (range, 2-6) treatments of ALA-PDT to achieve CR of the lesions. There was no significant difference in PDT outcomes between the 20 LED light-treated and 26 laser light-treated OEL lesions (P = 0.303). When the 42 CR OEL lesions were pooled together, we found that smaller lesions (greatest diameter <1.5 cm) and lesions with thinner surface keratin (keratin layer < or =30 microm) needed significantly fewer mean treatment number of PDT to achieve a CR than the larger lesions (P = 0.000) and lesions with thicker surface keratin (P = 0.000), respectively. Topical ALA-PDT using either the LED or laser light is an effective treatment modality for OEL lesions. There is no significant difference in clinical outcomes of OEL lesions treated with PDT using either the LED or laser light.
    Lasers in Surgery and Medicine 10/2009; 41(9):628-33. · 2.46 Impact Factor
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    ABSTRACT: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. 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. 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. 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.
    Journal of Oral Pathology and Medicine 08/2009; 38(8):651-6. · 2.06 Impact Factor
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    ABSTRACT: Oral leukoplakia (OL) is a common oral precancerous lesion. Cotton-swab cryotherapy (CSC) is commonly used for treating skin lesions but is rarely used for treating OL lesions. Sixty OL lesions were treated by CSC once every 2 weeks until complete regression (CR) of the lesion had been achieved. CR was achieved in all 60 OL lesions after an average of 6.3 treatments with cryotherapy. The number of CSC treatments required to achieve CR was significantly fewer for OL lesions on oral mucosal sites other than the tongue, those <2 cm2, those with epithelial dysplasia, and those with a surface keratin thickness of <55 microm. Multivariate analyses showed that only the location and area of the OL lesions were independent factors influencing the number of CSC treatments required to achieve CR. For OL lesions with a mean surface area of < or = 1.8 cm2, CR can be achieved with fewer than 7 CSC treatments on average. CSC is a simple, safe, easy, conservative, and acceptable treatment modality for OL lesions.
    Head & Neck 03/2009; 31(8):983-8. · 2.83 Impact Factor
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    ABSTRACT: A swept-source optical coherence tomography system is used to clinically scan oral precancer and cancer patients for statistically analyzing the effective indicators of diagnosis. Three indicators are considered, including the standard deviation (SD) of an A-mode scan signal profile, the exponential decay constant (alpha) of an A-mode-scan spatial-frequency spectrum, and the epithelium thickness (T) when the boundary between epithelium and lamina propria can still be identified. Generally, in abnormal mucosa, the standard deviation becomes larger, the decay constant of the spatial-frequency spectrum becomes smaller, and epithelium becomes thicker. The sensitivity and specificity of the three indicators are discussed based on universal and individual relative criteria. It is found that SD and alpha are good diagnosis indicators for moderate dysplasia and squamous cell carcinoma. On the other hand, T is a good diagnosis indicator for epithelia hyperplasia and moderate dysplasia.
    Optics Express 10/2008; 16(20):15847-62. · 3.55 Impact Factor
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    ABSTRACT: This study used an immunohistochemical technique to examine the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in 84 specimens of oral squamous cell carcinoma (OSCC), 106 specimens of oral epithelial dysplasia (OED, 32 mild, 44 moderate, and 30 severe OED cases), and 20 specimens of normal oral mucosa (NOM). We found that the mean RCAS1 labeling indices (LIs) increased significantly from NOM (12+/-5%) through mild OED (31+/-13%), moderate OED (44+/-17%), and severe OED (56+/-18%) to OSCC samples (68+/-20%, p<0.001). A significant correlation was found between the higher mean RCAS1 LI and OSCCs with larger tumor size (p=0.001), positive lymph node metastasis (p<0.001), or more advanced clinical stages (p<0.001). Positive lymph node metastasis (p=0.0073) and RCAS1 LI > or = 60% (p=0.048) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a RCAS1 LI > ot = 60% had a significantly poorer cumulative survival than those with a RCAS1 LI<60% (log-rank test, p=0.0113). We conclude that the expression of RCAS1 is an early event in oral carcinogenesis. The RCAS1 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.
    Oral Oncology 08/2008; 44(8):759-66. · 2.70 Impact Factor
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    ABSTRACT: Our previous studies showed that oral verrucous hyperplasia (OVH) lesions can be successfully treated with a topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) protocol using a 635-nm light-emitting diode light source. In this study, we report the clinical outcomes of 36 OVH lesions treated by this protocol and assess what clinicopathological parameters of OVH lesions could influence PDT treatment outcomes. We found that all the 36 OVH lesions showed complete response (CR) after an average of 3.8 (range, 1-6) treatments of topical ALA-PDT. OVH lesions with an clinical appearance of a mass, with the greatest diameter <1.5 cm, with the pink color, with epithelial dysplasia, or with the surface keratin layer < or =40 microm needed significantly less mean treatment numbers of PDT to achieve a CR than OVH lesions with an outer appearance of a plaque or a combination type of peripheral plaque and central mass (p=0.000), with the greatest diameter > or =1.5 cm (p=0.011), with the white color (p=0.000), without epithelial dysplasia (p=0.043), or with the surface keratin layer > 40 microm(p=0.003), respectively. Multivariate analysis showed that only the clinical appearance of OVH lesions was the independent factor (p=0.0069). We conclude that complete regression of OVH lesions can be achieved by less than seven treatments of topical ALA-PDT once a week. The PDT treatment outcome for OVH depends on the outer appearance, size, color, epithelial dysplasia, and surface keratin thickness of the lesion.
    Oral Oncology 07/2008; 44(6):595-600. · 2.70 Impact Factor
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    ABSTRACT: Central ossifying fibroma (COF) is the most common benign fibro-osseous lesion of the jaw. This retrospective study evaluated the clinical and histopathologic features of 28 COFs in Taiwanese patients. Twenty-eight consecutive cases of COF were collected from 1988 to 2006. The clinical data and microscopic features of these cases were reviewed and analyzed. The mean age of patients at the time of diagnosis was 34 years. There were six male and 22 female patients. Twenty-six (93%) cases were found in the mandible and two (7%) in the maxilla. The most common sites for COFs were the molar region (17 cases, 61%), followed by the premolar (8 cases, 28%), and incisor/canine (3 cases, 11%) regions. Bone swelling or expansion (96%, 26/27) was the most frequent clinical presentation. Six (21%) COFs presented as a radiolucent lesion, 17 (61%) as a mixed lesion, and five (18%) as a radio-opaque lesion. No recurrence of the lesion was found after surgical excision in this series. Microscopically, COFs showed trabeculae of woven bone (25 cases) and/or lamellar bone (5 cases) and/or spherules of cementoid (19 cases) in a cellular fibrous connective tissue stroma. The stromal component was highly cellular in 21 cases, moderately cellular in seven cases, prominently vascular in 11, and collagenous in six. COFs occur more frequently in female patients and in those in the second to fourth decades of life. The most commonly affected site is the mandible, especially the molar region. The majority of COF lesions present as a well-defined, mixed lesion radiographically. Most COFs can be treated by conservative surgical excision without subsequent recurrence.
    Journal of the Formosan Medical Association 05/2008; 107(4):288-94. · 1.00 Impact Factor
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    ABSTRACT: The epithelial cell adhesion molecule (Ep-CAM) is involved in cell signaling, migration, proliferation, cell-cycle regulation, and cancer metastasis. This study used an immunohistochemical technique to examine the expression of Ep-CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM). We found that the mean Ep-CAM labeling indices (LIs) decreased significantly from NOM (80 +/- 18%) and mild OED (76 +/- 14%) through moderate OED (66 +/- 22%) and severe OED (55 +/- 20%) to OSCC samples (46 +/- 16%, P < 0.001). A significant correlation was found between the lower mean Ep-CAM LI and OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.022), more advanced clinical stages (P < 0.001), cancer recurrence (P = 0.021), or extracapsular spread of lymph node (P = 0.015). However, only Ep-CAM LI < 50% (P < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan-Meier curve showed that OSCC patients with an Ep-CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep-CAM LI > or = 50% (P < 0.00001, log-rank test). We conclude that the decreased expression of Ep-CAM protein is an early event in oral carcinogenesis. The Ep-CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.
    Journal of Oral Pathology and Medicine 03/2008; 38(1):87-93. · 2.06 Impact Factor
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    ABSTRACT: Overexpression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers. This study examined the expression of HIF-1 alpha in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry. We found that the mean nuclear HIF-1 alpha labeling indices (LIs) increased significantly from NOM (9 +/- 6%) through mild OED (25 +/- 18%), moderate OED (41 +/- 27%), and severe OED (42 +/- 22%) to OSCC samples (55 +/- 23%, P < 0.001). A significant correlation was found between the higher mean nuclear HIF-1 alpha LI and OSCCs with larger tumor size (P < 0.001), regional lymph node metastasis (P < 0.001), or more advanced clinical stages (P < 0.001). Only larger tumor size (P = 0.002) and nuclear HIF-1 alpha LI >or= 60% (P = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a nuclear HIF-1 alpha LI >or= 60% had a significantly poorer cumulative survival than those with a nuclear HIF-1 alpha LI < 60% (log-rank test, P = 0.022). We conclude that the expression of HIF-1 alpha is an early event in oral carcinogenesis. The nuclear HIF-1 alpha LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.
    Journal of Oral Pathology and Medicine 02/2008; 37(1):18-25. · 2.06 Impact Factor
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    ABSTRACT: Incisional biopsy is accepted by most clinicians as a dependable way of assessing the nature of oral leukoplakia (OL). The aim of the present study was to investigate its reliability and analyze risk factors associated with underdiagnosis from incisional biopsy. A cross-sectional retrospective study was conducted in 242 patients with a clinical diagnosis of OL. The discrepancy between provisional diagnosis (from incisional biopsy) and definitive diagnosis (from resection specimen) was analyzed and correlated with clinical variables. Patients who had incisional biopsy taken from a single location and those who received multiple-site biopsies were analyzed separately. In the 200 cases receiving single-site biopsy, the agreement rate between provisional and definitive diagnoses was only 56%, and underdiagnosis from incisional biopsy was noted in 29.5% of patients. Underdiagnosis rate in the 42 patients receiving multiple-site biopsies was significantly lower (11.9%; P < .05). The rate of unexpected carcinoma in resection specimen was also significantly lower in the multiple-biopsy patients than in the single-biopsy patients (2.4% vs. 12.0%; P < .05). For the single-biopsy group, multivariate analysis revealed that clinical appearance significantly influenced the risk of underdiagnosis and unexpected carcinoma (both P < .05). Compared with homogeneous lesions, nonhomogeneous OL were more prone to be underdiagnosed (adjusted odds ratio [AOR] 2.36, 95% confidence interval [CI] 1.16-4.82) and have carcinoma undetected by incisional specimen (AOR 15.94, 95% CI 2.09-121.72). Incisional biopsy was found to have limitations in the assessment of OL, especially for nonhomogeneous lesions. Clinicians should be conscious of the possible underdiagnosis from incisional biopsy, and multiple biopsies should be taken whenever they think that it is necessary.
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 08/2007; 104(2):217-25. · 1.50 Impact Factor
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    ABSTRACT: Because of its close proximity to teeth and periodontium, gingival squamous cell carcinoma (SCC) can sometimes mimic tooth-related benign inflammatory conditions, resulting in misdiagnosis. In this study we report a case of gingival SCC that mimicked a dentoalveolar abscess of endodontic origin in its early presentation. The course and treatment of this case is discussed and a brief review of the literature is presented. Because many patients with gingival SCC visit dentists as their initial professional contact, it is hoped that the case can serve as a reminder for dentists to keep the possibility of carcinoma in mind when examining intraoral lesions.
    Journal of Endodontics 03/2007; 33(2):177-80. · 2.93 Impact Factor
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    ABSTRACT: This study used an immunohistochemical technique to examine the expression of human telomerase reverse transcriptase (hTERT) protein in 82 specimens of OSCC, 116 specimens of oral epithelial dysplasia (OED), and 21 specimens of normal oral mucosa (NOM). The cytoplasmic and nuclear hTERT staining intensity (SI; 0, no staining; 1, weak; 2, moderate; 3, strong), labeling indices (LIs, defined as the percentage of positive cells in total cells), and labeling scores (LSs, defined as LI x SI) in OSCC, OED, and NOM samples were calculated and compared among groups. The correlation between the cytoplasmic or nuclear hTERT LS in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. The mean cytoplasmic hTERT LSs increased significantly from NOM (87+/-17%) through OED (95+/-18%) to OSCC samples (114+/-33%, p=0.000). The mean nuclear hTERT LSs also increased from NOM (80+/-14%) to OED (91+/-20%) and then decreased to OSCC samples (86+/-35%) with no statistically significant difference among the 3 groups. A significant correlation was found between the higher mean cytoplasmic hTERT LSs and OSCCs occurring in male patients (p=0.023), with larger tumor sizes (T3 and T4, p=0.048), with more advanced clinical stages (stages 3 and 4, p=0.033), or from patients with areca quid chewing (p= 0.029), cigarette smoking (p=0.027), or alcohol drinking habit (p=0.025). In addition, OSCC patients with nuclear hTERT LSs greater than 100% were prone to have a higher recurrence rate (p=0.044) and a lower 5-year survival rate (p=0.011). Our results indicate that the increased expression of hTERT protein is an early event in oral carcinogenesis and hTERT may be a biomarker for OSCCs. Measuring the amount of cytoplasmic or nuclear expression of hTERT in OSCC samples may predict the oral cancer progression, recurrence, and prognosis in Taiwan.
    Oral Oncology 03/2007; 43(2):122-9. · 2.70 Impact Factor

Publication Stats

260 Citations
47.62 Total Impact Points

Institutions

  • 2010–2014
    • Chung Shan Medical University
      臺中市, Taiwan, Taiwan
  • 2005–2011
    • National Taiwan University
      • • Graduate Institute of Clinical Dentistry
      • • Department of Dentistry
      • • College of Medicine
      Taipei, Taipei, Taiwan
  • 2008
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2005–2008
    • National Taiwan University Hospital
      • School of Dentistry
      Taipei, Taipei, Taiwan