Significantly higher serum tumor marker levels in patients with oral submucous fibrosis.

BACKGROUND/PURPOSE: Our previous study showed that carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin are significantly higher in patients with oral potentially malignant disorders (OPMDs including oral leukoplakia, oral erythroleukoplakia, and oral verrucous hyperplasia) than in healthy controls (HCs). Oral submucous fibrosis (OSF) is also recognized as an OPMD. This study evaluated whether these three serum tumor marker levels were also significantly higher in OSF patients than in HCs. MATERIALS AND METHODS: The serum CEA, SCC-Ag, and ferritin levels in 41 OSF patients and 164 HCs were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. RESULTS: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 41 OSF patients than in 164 HCs (all P-values < 0.05). Moreover, 41 OSF patients had significantly higher serum positive rates of CEA (39.0%), SCC-Ag (19.5%), and ferritin (53.7%) than 164 HCs (all P-values < 0.05). Of the 41 OSF patients, 26 (63.4%), 7 (17.1%), and 2 (4.9%) had serum positivities of one, two, or three tumor markers including CEA, SCC-Ag, and ferritin, respectively. CONCLUSION: There are significantly higher mean serum CEA, SCC-Ag, and ferritin levels and significantly higher serum positive rates of CEA, SCC-Ag, and ferritin in OSF patients than in HCs. The serum CEA, SCC-Ag, and ferritin levels may be served as tumor markers for evaluation of malignant potential of OSF lesions.

Serum levels and positive rates of tumor biomarkers in oral precancer patients.

BACKGROUND/PURPOSE: Several previous studies have reported higher serum tumor marker levels in patients with oral or head and neck squamous cell carcinomas. This study evaluated whether 232 patients with oral precancerous lesions (oral precancer patients) had significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin levels than healthy control subjects. METHODS: The serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. RESULTS: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients than in 187 healthy control subjects (all P-values < 0.05). Moreover, 232 oral precancer patients had significantly higher serum positive rates of CEA (47.4%), SCC-Ag (13.8%), and ferritin (52.2%) than 187 healthy control subjects (all P-values < 0.05). Of the 232 oral precancer patients, 121 (52.1%), 56 (24.1%), and 10 (4.3%) had serum positivities of one, two, or three tumor markers including CEA, SCC-Ag, and ferritin, respectively. CONCLUSION: There are significantly higher mean serum CEA, SCC-Ag, and ferritin levels and significantly higher serum positive rates of CEA, SCC-Ag, and ferritin in oral precancer patients than in healthy control subjects. The serum CEA, SCC-Ag, and ferritin levels are of diagnostic value and may be potential tumor markers for the screening of oral precancer patients.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with vitamin B12 deficiency.

BACKGROUND/PURPOSE: Our previous study found that 56 of 1064 atrophic glossitis (AG) patients have vitamin B12 deficiency. This study assessed whether the AG patients with vitamin B12 deficiency (B12D/AG patients) had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 56 B12D/AG patients and 532 healthy control subjects were measured and compared. RESULTS: We found that 56 B12D/AG patients had significantly lower mean blood Hb and serum iron levels as well as significantly higher mean corpuscular volume (MCV) and mean serum homocysteine level than healthy control subjects (all P-values < 0.05). Moreover, 56 B12D/AG patients had significantly higher frequencies of macrocytosis (53.6%), blood Hb (64.3%), iron (26.8%), and folic acid (3.6%) deficiencies, hyperhomocysteinemia (89.3%), and serum GPCA positivity (55.4%) than 532 healthy control subjects (all P-values < 0.005). In addition, of 36 anemic B12D/AG patients, 22 (61.1%) had pernicious anemia (PA), 6 (16.7%) had macrocytic anemia other than PA, 4 (11.1%) had normocytic anemia, 3 (8.3%) had iron deficiency anemia (IDA), and one (2.8%) had microcytic anemia other than IDA and thalassemia trait-induced anemia. CONCLUSION: We conclude that B12D/AG patients have significantly higher frequencies of macrocytosis, blood Hb, iron, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects. PA is the most common type of anemia in our B12D/AG patients.

Clinical outcomes of oral cancer patients who survive for more than 5 years in Taiwan.

BACKGROUND/PURPOSE: Oral cancer patients who survive for more than 5 years are supposed to have a reduced local cancer recurrence rate and survive longer. This study evaluated whether oral cancer patients who survived for more than 5 years might have reduced rates of local cancer recurrence, development of the second or third primary oral cancer, or the late regional cervical lymph node metastasis. METHODS: This study analyzed the clinical outcomes of 127 oral cancer patients (101 men and 26 women; mean age, 50.8 ± 12.1 years) who survived for more than 5 years after proper treatments of the initial primary oral cancers. RESULTS: The 127 primary oral cancers included 117 squamous cell carcinomas (SCCs), 7 mucoepidermoid carcinomas, and 3 others. Of the 127 oral cancer patients who survived for more than 5 years, 47 survived for 5-9 years, 45 for 10-14 years, 22 for 15-19 years, 10 for 20-24 years, two for 25-29 years, and one for 30 years. Ten patients had local cancer recurrence 5.4 years-13.7 years, 12 patients had a second or a third primary oral cancer 3.6 years-17.2 years, and one mucoepidermoid carcinoma patient had a late regional cervical lymph node metastasis 11.9 years after total excision of the initial primary oral cancers. CONCLUSION: Oral cancer patients who survive for more than 5 years may still have local cancer recurrence, the second or third primary oral cancer, or the late regional cervical lymph node metastasis but with a reduced rate.

Gastric parietal cell and thyroid autoantibodies in oral precancer patients.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) may be present in oral mucosal disease patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 131 oral precancer patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects. RESULTS: We found that 131 oral precancer patients had higher frequencies of serum GPCA (10.7% vs. 2.3%, P = 0.012, statistically significant), TGA (4.6% vs. 2.3%, P = 0.498), and TMA (8.4% vs. 2.3%, P = 0.054, marginal significance) positivities than 131 healthy control subjects. We also found that 1 (0.8%), 6 (4.6%), and 16 (12.2%) oral precancer patients had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) autoantibody in their sera, respectively. Of 10 TGA/TMA-positive oral precancer patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 80%, 10%, and 10% of these 10 TGA/TMA-positive oral precancer patients had normal, lower, and higher serum TSH levels, respectively. We also found a significantly higher GPCA positive rate in 26 smokers consuming >20 cigarettes per day than in 61 smokers consuming ≤20 cigarettes per day (P = 0.008). CONCLUSION: Approximately 17.6% of 131 oral precancer patients have serum GPCA/TGA/TMA positivity. Only approximately 20% of TGA/TMA-positive oral precancer patients have either hypothyroidism or hyperthyroidism.

Blood profile of atrophic glossitis patients with thyroglobulin antibody/thyroid microsomal antibody positivity but without gastric parietal cell antibody positivity.

BACKGROUND/PURPOSE: Our previous study found that 304 of 1064 atrophic glossitis (AG) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity but without gastric parietal cell antibody positivity (GPCAÖ¾TGA+/TMA+AG patients). This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 304 GPCAÖ¾TGA+/TMA+AG patients and 476 GPCA-negative, TGA-negative, and TMA-negative AG patients (GPCAÖ¾TGAÖ¾TMAÖ¾AG patients) or 532 healthy control subjects. RESULTS: We found significantly lower MCV and lower mean blood Hb and iron levels as well as significantly greater frquencies of microcytosis, macrocytosis, blood Hb, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia in 304 GPCAÖ¾TGA+/TMA+AG patients than in 532 healthy control subjects. However, no significant differences in the MCV and mean blood Hb, iron, vitamin B12, folic acid, and homocysteine leve1s as well as no significant differences in the frequencies of microcytosis, macrocytosis, blood Hb, iron, and folic acid deficiencies, and hyperhomocysteinemia were discovered between 304 GPCAÖ¾TGA+/TMA+AG patients and 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. The 304 GPCAÖ¾TGA+/TMA+AG patients had a significantly greater frquency of serum vitamin B12 deficiency than 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. CONCLUSION: The disease of AG itself plays a significant role in causing anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients. However, the serum TGA/TMA-positivity is not significantly associated with anemia, serum iron and folic acid deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients.

Significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in patients with Behcet's disease.

BACKGROUND/PURPOSE: Behcet's disease (BD) patients may have one or more hematinic deficiencies. This study evaluated whether there were significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in BD patients. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations in 63 BD patients were measured and compared with the corresponding levels in 126 age- and sex-matched healthy control subjects. RESULTS: We found that 30.2%, 34.9%, 6.3%, 6.3%, and 14.3% of 63 BD patients had hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia, respectively. Both 63 BD and 19 major-typed RAS/BD patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than 126 healthy control subjects (all P-values < 0.05). Moreover, 44 minor-typed RAS/BD patients had significantly higher frequencies of hemoglobin and iron deficiencies than 126 healthy control subjects (both P-values < 0.001). Of the 19 anemic BD patients, one had pernicious anemia, one had macrocytic anemia, 12 had normocytic anemia, four had iron deficiency anemia, and one had thalassemia trait-induced anemia. CONCLUSION: There are significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in BD patients. The normocytic anemia is the most common type of anemia in our 63 BD patients. We suggest that supplementations of vitamin BC capsules plus deficient vitamin B12 and/or folic acid may reduce the abnormally high serum homocysteine level to a relatively lower level in BD patients with hyperhomocysteinemia.

S100 protein-positive Langerhans cells in 80 dentigerous cysts.

BACKGROUND/PURPOSE: Langerhans cells (LCs) are antigen-presenting cells. This study assessed the LC counts in 80 dentigerous cysts (DCs). MATERIALS AND METHODS: The S100-positive LC numbers in the lining epithelia and subepithelial connective tissues were counted at 80 DC sites without inflammation, 33 DC sites with mild/moderate inflammation, and 9 DC sites with severe inflammation from 80 DC specimens. RESULTS: The mean S100-positive LC counts in the lining epithelia and subepithelial connective tissues increased significantly from no inflammation (0.6 ± 0.6 and 0.7 ± 0.6 cell/high-power field or HPF, respectively) through mild/moderate inflammation (8.1 ± 2.0 and 4.5 ± 2.3 cells/HPF, respectively) to severe inflammation DC sites (21.0 ± 7.0 and 11.1 ± 6.5 cells/HPF, respectively; P-value < 0.001). DC sites with inflammation had thicker lining epithelia than those without inflammation. Moreover, the mean LC counts in the lining epithelia and subepithelial connective tissues of DCs were significantly higher in the thicker lining epithelium (>50 µm) group (8.6 ± 7.1 and 4.8 ± 4.5 cells/HPF, respectively) than in the thinner lining epithelium (≦50 µm) group (0.6 ± 0.6 and 0.6 ± 0.6 cells/HPF, respectively; both P-values < 0.001). CONCLUSION: A significant association of high-grade inflammation and thick lining epithelium with the increased LC number in DCs is found. Very few LCs in the lining epithelia of DCs without inflammation indicate the reduced immunosurveillance ability against DC lining epithelial cells in DC patients. It needs further studies to confirm the role of reduced immunosurveillance in the enlargement of the DC.

Differences in oral habit and lymphocyte subpopulation affect malignant transformation of patients with oral precancer.

BACKGROUND/PURPOSE: In Taiwan, the combination of betel quid chewing, alcohol consumption, and smoking habits increases oral cancer risk by 123-fold compared to persons without these habits. Lymphocyte populations in patients may potentially affect the malignant transformation of oral precancer. METHODS: A total of 28 patients with oral precancer from our previous cohort were enrolled in this study, and their personal information and oral habits were documented. Their lymphocyte populations (CD4+, CD8+, CD19+, and CD56+) and activation markers (CD25 and CD69) were determined by flow cytometry from 1999 to 2004. After follow up till December 2014, data of patients with/without malignant transformation were recorded, and the relation between oral habits and percentage of initial lymphocyte markers was evaluated using the Student t test and Fisher's exact test. RESULTS: Ten precancer patients developed oral squamous cell carcinoma with a mean period of malignant transformation of 6.8 ± 2.1 years. Patients with malignant transformation had a mean age of 48.4 ± 5.0 years (n = 10), relatively more than that of patients without malignant transformation (41.6 ± 6.3 years, n = 18) (p < 0.05). An increase was noted in the population of peripheral blood mononuclear cells expressing CD4+CD69+, CD19+CD69+, and CD56+CD69+ (p < 0.05) in precancer patients with malignant transformation. Alcohol consumption showed an association with the malignant transformation of patients with precancer (p = 0.030), whereas betel quid and smoking showed little effect. CONCLUSION: These results suggest that age, alcohol consumption, and early activation of T cells, B cells, and natural killer cells are crucial in the malignant transformation of oral precancer. Analysis of patient's lymphocyte populations may help predict the malignant transformation of oral precancer.

Non-calcifying and Langerhans cell-rich variant of calcifying epithelial odontogenic tumor.

This study reported the clinicopathological features, treatment and prognosis of nine cases of noncalcifying and Langerhans cell (LC)-rich calcifying epithelial odontogenic tumor (CEOT) collected from the English literature. Of the nine cases, seven were intraosseous and two were extraosseous. All nine tumors were found in Asian patients. The age of the nine patients ranged from 20 years to 58 years with a mean age of 41 years. There were five female and four male patients. The seven intraosseous cases included six in the anterior and premolar region of the maxilla and one in the posterior region and ascending ramus of the mandible. The two extraosseous cases were located at the upper lateral incisor and premolar gingivae, respectively. Of the seven intraosseous cases, five showed unilocular and two multilocular radiolucency without foci of calcification. Six of the seven intraosseous cases showed resorption of the tooth roots in the tumor-involved region. Histologically, noncalcifying and LC-rich CEOTs were composed of small nests and thin strands of tumor epithelial cells with a relatively high number of LCs among them. This was the reason why we classed these nine cases as noncalcifying and LC-rich CEOTs. Two extraosseous cases received total excision of the gingival mass. For the seven intraosseous cases, four accepted partial maxillectomy or mandibulectomy, two received total excision or enucleation, and one underwent curettage. The six cases with the follow-up information available showed no tumor recurrence after a follow-up period of 6 months to 10 years.

Clinical effectiveness, toxicity, and failure patterns of helical tomotherapy for postoperative oral cavity cancer patients.

BACKGROUND: The outcome of postoperative high- and intermediate-risk oral cavity cancer (OCC) patients receiving helical tomotherapy (HT) remains limited. MATERIALS AND METHODS: Between November 2006 and November 2012, 53 postoperative high- and intermediate-risk OCC patients treated with HT were enrolled. RESULTS: The 4-year locoregional, local, and regional control rates were 66%, 76.4%, and 94.3%, respectively. The 4-year locoregional control rates of oral tongue and buccal mucosa cancer were 88.3% and 37.1%, respectively (P=0.012). Eleven (20.8%) patients experienced locoregional failure. In-field failure occurred in six of 53 (11.3%) in the primary area and three of 53 (5.7%) in the regional lymph-node area. No marginal failure was noted. Two of 53 (3.8%) experienced out-of-field failure. The rates of grade 3 dermatitis, mucositis, and dysphagia were 11%, 34%, and 13%, respectively. No grade 3 xerostomia was noted. Grade 2 xerostomia was 33% at month 6 and declined to 0 at month 48. A rate of 56% of grade 2 trismus at month 6 was noted, and declined to around 30% after 2 years. No grade 3 trismus was noted after 2 years. CONCLUSION: HT as a postoperative modality provided satisfying results, especially for xerostomia and trismus, and was impressive in high- and intermediate-risk OCC patients receiving postoperative HT.