Oral cancer: A multicenter study.

BACKGROUND: To determine the prevalence and clinicopathologic features of the oral cancer patients. MATERIAL AND METHODS: Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. RESULTS: Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. CONCLUSIONS: Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Do all the patients with gastric parietal cell antibodies have pernicious anemia?

OBJECTIVE: This study evaluated whether all the patients with serum gastric parietal cell antibody (GPCA) positivity had pernicious anemia (PA). MATERIALS AND METHODS: The blood hemoglobin (Hb), iron, and vitamin B12 concentrations, and mean corpuscular volume (MCV) in 124 GPCA-positive patients were measured and compared with the corresponding data in 124 age- and sex-matched healthy controls. PA was defined by World Health Organization (WHO) as having an Hb concentration < 13 g dl(-1) for men and < 12 g dl(-1) for women, an MCV ≥ 100 fl, and a serum vitamin B12 level < 200 pg ml(-1) . RESULTS: We found that 20, 25, and 20 GPCA-positive patients had deficiencies of Hb (men < 13 g dl(-1) , women < 12 g dl(-1) ), iron (<60 µg dl(-1) ), and vitamin B12 (<200 pg ml(-1) ), respectively. Moreover, 16 GPCA-positive patients had abnormally high MCV (≥ 100 fl). GPCA-positive patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency and of abnormally high MCV (all P-values < 0.001) than healthy controls. However, only 12.9% of 124 GPCA-positive patients were diagnosed as having PA by the WHO definition. CONCLUSION: Only 12.9% of GPCA-positive patients are discovered to have PA by the WHO definition.

Significant reduction of homocysteine level with multiple B vitamins in atrophic glossitis patients.

OBJECTIVE: This study evaluated whether supplementations of different vitamins and iron could reduce the serum homocysteine levels in 91 atrophic glossitis (AG) patients. MATERIALS AND METHODS: Atrophic glossitis (AG) patients with concomitant deficiencies of vitamin B12 only (n = 39, group I), folic acid only (n = 10, group II), iron only (n = 9, group III), or vitamin B12 plus iron (n = 19, group IV) were treated with vitamin BC capsules plus deficient hematinics. AG patients without definite hematinic deficiencies (n = 14, group V) were treated with vitamin BC capsules only. The blood homocysteine and hematinic levels at baseline and after treatment till all oral symptoms had disappeared were measured and compared by paired t-test. RESULTS: Supplementations with vitamin BC capsules plus corresponding deficient hematinics for groups I, II, III, IV patients and with vitamin BC capsules only for group V patients could reduce the high serum homocysteine levels to significantly lower levels after a mean treatment period of 8.3-11.6 months (all P-values < 0.05). CONCLUSION: Supplementations with vitamin BC capsules plus corresponding deficient hematinics or with vitamin BC capsules only can reduce the high serum homocysteine levels to significantly lower levels in AG patients.

Arecoline-stimulated placenta growth factor production in gingival epithelial cells: modulation by curcumin.

OBJECTIVE: Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer. MATERIALS AND METHODS: This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PlGF) protein or mRNA expression in human gingival epithelial S-G cells. RESULTS: Arecoline, a major areca nut alkaloid and an oral carcinogen, could stimulate PlGF protein synthesis in S-G cells in a dose- and time-dependent manner. The levels of PlGF protein secretion increased about 3.1- and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) and ERK inhibitor PD98059, but not NF-κB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580, and PI3-K inhibitor LY294002, significantly reduced arecoline-induced PlGF protein synthesis. ELISA analyses demonstrated that NAC and PD98059 reduced about 43% and 38% of the arecoline-induced PlGF protein secretion, respectively. However, combined treatment with NAC and PD98059 did not show additive effect. Moreover, 10 µM curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 µM curcumin completely blocked arecoline-induced PlGF mRNA expression. CONCLUSION: Arecoline-induced PlGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.

Modulation of serum gastric parietal cell antibody level by levamisole and vitamin B12 in oral lichen planus.

OBJECTIVES: The objective of this study was to test the efficacy of three different treatment modalities on the reduction of serum anti-gastric parietal cell autoantibody (GPCA) level in GPCA-positive oral lichen planus (OLP) patients. MATERIALS AND METHODS: Of 147 GPCA-positive OLP patients, 100 were treated with levamisole plus vitamin B12, 10 with vitamin B12 only and 37 with levamisole only. The serum GPCA levels in 147 OLP patients were measured at baseline and after treatment. RESULTS: Treatment with levamisole plus vitamin B12 for a period of 2-50 months and treatment with vitamin B12 only for a period of 4-44 months could effectively reduce the high serum GPCA level to undetectable level in 100 and 10 OLP patients, respectively. However, treatment with levamisole only for a period of 2-50 months could not modulate the high mean serum GPCA titer to a significantly lower level in 37 OLP patients. A 92% GPCA recurrence rate was found in 25 OLP patients receiving no further vitamin B12 treatment during the GPCA-negative remission period. CONCLUSION: For GPCA-positive OLP patients, treatment modality containing vitamin B12 can effectively reduce the high serum GPCA level to undetectable level. OLP patients with underlying autoimmune atrophic gastritis trait should receive a maintenance vitamin B12 treatment for life.

Malignant amelanotic melanoma developing from an intradermal naevus in a patient with oculocutaneous albinism.

A 43-year-old Taiwanese man who had oculocutaneous albinism type 1 presented with a tumorous lesion over the pubic region. Within the tumour, there was a small pinkish plaque. Histopathologically, the tumour revealed benign naevus cells in the upper dermis and atypical malignant tumour cells in the deeper dermis. Immunohistochemistry using HMB-45 showed intensive positive staining in the deeper dermal tumour cells. Amelanotic malignant melanoma (MM) originating from a pre-existing intradermal naevus was diagnosed.

Miliarial gout: a rare presentation of extensive cutaneous tophi.

Gout is a systemic disorder characterized by hyperuricemia and recurrent arthritis, most involvement of ankles, midfoot joint and first metatarsophalangeal joint, with monosodium urate crystals deposition in synovial fluid and other tissues. We present a case of 53-year-old male, who had several nontender, white-yellow papules and plaques over his elbows, knees and arms with chalk-like substances and crust on inflammatory base wax and wane in the past 2 years. Upon histopathology examination of the skin lesions, it reported as intradermal urate tophi and miliarial gout was diagnosed. This case highlights the importance of considering unusual cutaneous tophi in the differential diagnosis of deposition disorders.

Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit.

Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian countries. BQ chewing has strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in production of antigenicity. BQ ingredients are also shown to induce keratinocyte inflammation by stimulating the production of prostaglandins, TNF-alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in keratinocytes. These events may provoke tissue inflammation, early cell-mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ components also directly affect the functional activities of immunocompotent cells, and moreover tumor cells may hypo-respond to the CMI via diverse mechanisms such as induction of apoptosis of lymphocytes, induction of production of suppressor T cells, downregulation of MHC molecules in tumor cells, etc. Clinically, an alteration in lymphocyte subsets, a decrease in total number of lymphocytes, and a reduction in functional activities of CMI have been observed in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to immune system may promote clonal selection of resistant tumor cells, leading to immune tolerance. Future studies on effects of BQ components on CMI and humoral immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ consumption, and other environmental exposure affect the immune status of patients with oral premalignant lesions or OC will help us to understand the immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.

Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer.

Both genetic and environmental factors are involved in the development of cancer; some phase I and II enzymes involved in the metabolism of carcinogens are polymorphic in genotypes. This case-control study focused on the interactions between oral cancer risk factors and genetic polymorphisms of cytochrome P-450 (CYP) 2E1 and glutathione S-transferase (GST) M1 and GSTT1. A total of 41 male oral cancer cases was recruited from National Taiwan University Hospital, and 123 healthy controls frequency-matched on ethnicity, sex, and age were recruited from residents living in Taipei City and Taipei County. History of cigarette smoking, alcohol drinking, and betel quid chewing was obtained through a standardized questionnaire interview, and genotypes of CYP2E1, GSTM1, and GSTT1 were determined by PCR. Cigarette smoking, alcohol drinking, and betel quid chewing were significantly associated with the risk of oral cancer in a dose-response relationship. All betel quid chewers smoked cigarettes in both the case and control groups. In the multiple logistic regression analysis, those who had null genotypes of GSTM1 and/or GSTT1 had an increased oral cancer risk compared with those who had non-null genotypes of both GSTM1 and GSTT1, showing a multivariate-adjusted odds ratio (OR) of 4.6 with a 95% confidence interval (CI) of 0.9-23.7 (P = 0.08). The CYP2E1 c1/c2 and c2/c2 genotypes were associated with a significantly increased oral cancer risk compared with the c1/c1 genotype among those who did not chew betel quid (OR, 4.7; 95% CI, 1.1-20.2), but not among betel quid chewers. Habitual alcohol drinking was associated with a significantly increased oral cancer risk, showing an OR of 3.0 (95% CI, 1.1-8.8). These results implied that there are gene-gene and gene-environment interactions in the development of oral cancer.