An improved 3-D attention CNN with hybrid loss and feature fusion for pulmonary nodule classification.

BACKGROUND AND OBJECTIVE: Lung cancer has the highest cancer-related mortality worldwide, and lung nodule usually presents with no symptom. Low-dose computed tomography (LDCT) was an important tool for lung cancer detection and diagnosis. It provided a complete three-dimensional (3-D) chest image with a high resolution.Recently, convolutional neural network (CNN) had flourished and been proven the CNN-based computer-aided diagnosis (CADx) system could extract the features and help radiologists to make a preliminary diagnosis. Therefore, a 3-D ResNeXt-based CADx system was proposed to assist radiologists for diagnosis in this study. METHODS: The proposed CADx system consists of image preprocessing and a 3-D CNN-based classification model for pulmonary nodule classification. First, the image preprocessing was executed to generate the normalized volumn of interest (VOI) only including nodule information and a few surrounding tissues. Then, the extracted VOI was forwarded to the 3-D nodule classification model. In the classification model, the RestNext was employed as the backbone and the attention scheme was embedded to focus on the important features. Moreover, a multi-level feature fusion network incorporating feature information of different scales was used to enhance the prediction accuracy of small malignant nodules. Finally, a hybrid loss based on channel optimization which make the network learn more detailed information was empolyed to replace a binary cross-entropy (BCE) loss. RESULTS: In this research, there were a total of 880 low-dose CT images including 440 benign and 440 malignant nodules from the American National Lung Screening Trial (NLST) for system evaluation. The results showed that our system could achieve the accuracy of 85.3%, the sensitivity of 86.8%, the specificity of 83.9%, and the area-under-curve (AUC) value was 0.9042. It was confirmed that the designed system had a good diagnostic ability. CONCLUSION: In this study, a CADx composed of the image preprocessing and a 3-D nodule classification model with attention scheme, feature fusion, and hybrid loss was proposed for pulmonary nodule classification in LDCT. The results indicated that the proposed CADx system had potential for achieving high performance in classifying lung nodules as benign and malignant.

One-stage pulmonary nodule detection using 3-D DCNN with feature fusion and attention mechanism in CT image.

BACKGROUND AND OBJECTIVE: Lung cancer is the most common cause of cancer-related death in the world. Low-dose computed tomography (LDCT) is a widely used modality in lung cancer detection. The nodule is an abnormal tissue and may evolve into lung cancer. Hence, it is crucial to detect nodules in the early detection stage. However, reviewing the LDCT scans to observe suspicious nodules is a time-consuming task. Recently, designing a computer-aided detection (CADe) system with convolutional neural network (CNN) architecture has been proven that it is helpful for radiologists. Hence, in this study, a 3-D YOLO-based CADe system, 3-D OSAF-YOLOv3, is proposed for nodule detection in LDCT images. METHODS: The proposed CADe system consists of data preprocessing, nodule detection, and non-maximum suppression algorithm (NMS). At first, the data preprocessing including the background elimination, the spacing normalization, and the volume of interest (VOI) extraction, are conducted to remove the non-lung region, normalize the image spacing, and divide LDCT image into numerous VOIs. Then, the VOIs are fed into the 3-D OSAF-YOLOv3 model, to detect the suspicious nodules. The proposed model is constructed by integrating the 3-D YOLOv3 with the one-shot aggregation module (OSA), the receptive field block (RFB), and the feature fusion scheme (FFS). Finally, the NMS algorithm is performed to eliminate the duplicated detection generated by the model. RESULTS: In this study, the LUNA-16 dataset composed 1186 nodules from 888 LDCT scans and the competition performance metric (CPM) are used to evaluate our CADe system. In the experiment results, the proposed system can achieve a sensitivities rate of 0.962 with the false positive rate of 8 and complete a CPM value of 0.905. Moreover, according to the ablation study results, the employment of OSA module, RFB, and FFS could improve the detection performance actually. Furthermore, compared to other start-of-the-art (SOTA) models, our detection system could also achieve the higher performance. CONCLUSIONS: In this study, a YOLO-based CADe system for nodule detection in CT image system integrating additional modules and scheme is proposed for nodule detection in LDCT. The result indicates that the proposed the modification can significantly improve detection performance.

Multi-energy level fusion for nodal metastasis classification of primary lung tumor on dual energy CT using deep learning.

Lymph node metastasis also called nodal metastasis (Nmet), is a clinically primary task for physicians. The survival and recurrence of lung cancer are related to the Nmet staging from Tumor-Node-Metastasis (TNM) reports. Furthermore, preoperative Nmet prediction is still a challenge for the patient in managing the surgical plan and making treatment decisions. We proposed a multi-energy level fusion model with a principal feature enhancement (PFE) block incorporating radiologist and computer science knowledge for Nmet prediction. The proposed model is custom-designed by gemstone spectral imaging (GSI) with different energy levels on dual-energy computer tomography (CT) from a primary tumor of lung cancer. In the experiment, we take three different energy level fusion datasets: lower energy level fusion (40, 50, 60, 70 keV), higher energy level fusion (110, 120, 130, 140 keV), and average energy level fusion (40, 70, 100, 140 keV). The proposed model is trained by lower energy level fusion that is 93% accurate and the value of Kappa is 86%. When we used the lower energy level images to train the fusion model, there has been a significant difference to other energy level fusion models. Hence, we apply 5-fold cross-validation, which is used to validate the performance result of the multi-keV model with different fusion datasets of energy level images in the pathology report. The cross-validation result also demonstrates that the model with the lower energy level dataset is more robust and suitable in predicting the Nmet of the primary tumor. The lower energy level shows more information of tumor angiogenesis or heterogeneity provided the proposed fusion model with a PFE block and channel attention blocks to predict Nmet from primary tumors.

Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors.

Mitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed. Clinical associations of TFAM and mtDNA encoded Electron Transport Chain (ETC) genes in regulating HNC tumourigenesis were also examined in HNC specimens. At cellular level, TFAM silencing led to an enhanced cell growth, motility and chemoresistance whereas enforced TFAM expression significantly reversed these phenotypic changes. These TFAM mediated cellular changes resulted from (1) metabolic reprogramming by directing metabolism towards aerobic glycolysis, based on the detection of less respiratory capacity in accompany with greater lactate production; and/or (2) enhanced ERK1/2-Akt-mTORC-S6 signalling activity in response to TFAM induced mtDNA perturbance. Clinical impacts of TFAM and mtDNA were further defined in carcinogen-induced mouse tongue cancer and clinical human HNC tissues; as the results showed that TFAM and mtDNA expression were significantly dropped in tumour compared with their normal counterparts and negatively correlated with disease progression. Collectively, our data uncovered a tumour-suppressing role of TFAM and mtDNA in determining HNC oncogenicity and potentially paved the way for development of TFAM/mtDNA based scheme for HNC diagnosis.

Dual energy CT image prediction on primary tumor of lung cancer for nodal metastasis using deep learning.

Lymph node metastasis (LNM) identification is the most clinically important tasks related to survival and recurrence from lung cancer. However, the preoperative prediction of nodal metastasis remains a challenge to determine surgical plans and pretreatment decisions in patients with cancers. We proposed a novel deep prediction method with a size-related damper block for nodal metastasis (Nmet) identification from the primary tumor in lung cancer generated by gemstone spectral imaging (GSI) dual-energy computer tomography (CT). The best model is the proposed method trained by the 40 keV dataset achieves an accuracy of 86 % and a Kappa value of 72 % for Nmet prediction. In the experiment, we have 11 different monochromatic images from 40∼140 keV (the interval is 10 keV) for each patient. When we used the model of 40 keV dataset, there has significant difference in other energy levels (unit of keV). Therefore, we apply in 5-fold cross-validation to explain the lower keV is more efficient to predict Nmet of the primary tumor. The result shows that tumor heterogeneity and size contributed to the proposed model to estimate whether absence or presence of nodal metastasis from the primary tumor.

Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer.

BACKGROUND: Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. METHODS: This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. RESULTS: Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p <  0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, Ktrans, and kep, showed strong linear correlations (p <  0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p <  0.001), and kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10- 3/min (p = 0.069), and kep > 900 10- 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. CONCLUSIONS: The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.

Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment.

Oral cancer (OC) is a serious health problem. Surgery is the best method to treat the disease but might reduce the quality of life of patients. Photodynamic therapy (PDT) may enhance quality of life but with some limitations. Therefore, the development of a new strategy to facilitate PDT effectiveness has become crucial. ATP-binding cassette G2 (ABCG2) is a membrane protein-associated drug resistance and stemness in cancers. Here, we examined whether ABCG2 plays an important role in regulating the treatment efficacy of PDT and whether ABCG2 inhibition by natural compounds can promote the effect of PDT in OC cells. Several head and neck cancer cells were utilized in this study. OECM1 and SAS cells were selected to investigate the relationship between ABCG2 expression and protoporphyrin IX (PpIX) accumulation. Western blot analysis, flow cytometry analysis, and survival probability were performed to determine PDT efficacy and cellular stemness upon treatment of different dietary compounds, including epigallocatechin gallate (EGCG) and curcumin. In this study, we found that ABCG2 expression varied in OC cells. Hypoglycemic culture for SAS cells enhanced ABCG2 expression as higher ABCG2 expression was associated with lower PpIX accumulation and cellular stemness in OC cells. In contrast, suppression of ABCG2 expression by curcumin and tea polyphenol EGCG led to greater PpIX accumulation and enhanced PDT treatment efficiency in OC cells. In conclusion, ABCG2 plays an important role in regulating the effect of PDT. Change in glucose concentration and treatment with natural compounds modulated ABCG2 expression, resulting in altered PDT efficacy for OC cells. These modulations raise a potential new treatment strategy for early-stage OCs.

Corrigendum: Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis.

[This corrects the article DOI: 10.3389/fonc.2020.00176.].

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis.

To support great demand of cell growth, cancer cells preferentially obtain energy and biomacromolecules by glycolysis over mitochondrial oxidative phosphorylation (OxPhos). Among all glycolytic enzymes, hexokinase (HK), a rate-limiting enzyme at the first step of glycolysis to catalyze cellular glucose into glucose-6-phosphate, is herein emphasized. Four HK isoforms, HK1-HK4, were discovered in nature. It was shown that HK2 expression is enriched in many tumor cells and correlated with poorer survival rates in most neoplastic cells. HK2-mediated regulations for cell malignancy and mechanistic cues in regulating head and neck tumorigenesis, however, are not fully elucidated. Cellular malignancy index, such as cell growth, cellular motility, and treatment sensitivity, and molecular alterations were determined in HK2-deficient head and neck squamous cell carcinoma (HNSCC) cells. By using various cancer databases, HK2, but not HK1, positively correlates with HNSCC progression in a stage-dependent manner. A high HK2 expression was detected in head and neck cancerous tissues compared with their normal counterparts, both in mouse and human subjects. Loss of HK2 in HNSCC cells resulted in reduced cell (in vitro) and tumor (in vivo) growth, as well as decreased epithelial-mesenchymal transition-mediated cell movement; in contrast, HK2-deficient HNSCC cells exhibited greater sensitivity to chemotherapeutic drugs cisplatin and 5-fluorouracil but are more resistant to photodynamic therapy, indicating that HK2 expression could selectively define treatment sensitivity in HNSCC cells. At the molecular level, it was found that HK2 alteration drove metabolic reprogramming toward OxPhos and modulated oncogenic Akt and mutant TP53-mediated signals in HNSCC cells. In summary, the present study showed that HK2 suppression could lessen HNSCC oncogenicity and modulate therapeutic sensitivity, thereby being an ideal therapeutic target for HNSCCs.

The learning experience of basic science and clinical dentistry by postgraduate students in Institute of Clinical Dentistry and Institute of Oral Biology.

BACKGROUND/PURPOSE: Students with different undergraduate trainings may have different responses after taking a combined course with both clinical and basic topics. This study investigated the learning experience of basic science and clinical dentistry by postgraduate students in Institute of Clinical Dentistry (ICD) and Institute of Oral Biology (IOB) after finishing the specific course. MATERIALS AND METHODS: Semi-structure questionnaire filled by internet process was used. The data were collected and analyzed statistically. RESULTS: Nineteen participants who took the course of "panel discussion of oral oncology" since 2014 to 2018 were included in this study. Of the 19 postgraduate students, 11 were from ICD and 8 from IOB. Both ICD and IOB students gave high scores for the items such as benefit for the research, appropriateness of the discussion topics, and suitableness of problem-based teaching model. ICD students tended to have better fitness of interdisciplinary learning (P > 0.05), better understanding of clinical topics (significant, P = 0.02), and a higher willing to recommend other students to take the course (P > 0.05) than IOB students. However, IOB students tended to have a better understanding of basic science topics than ICD students, although the difference was not significant (P > 0.05). CONCLUSION: Our problem-based and constructive teaching course and the selected topics are proper and helpful for students' future research. The students with the clinical training background are prone to have better understanding of clinical topics, while those with the basic science training tend to have better understanding of basic science topics.

Parasympathetic effect of deep pressure input on third molar extraction in adolescents.

BACKGROUD/PURPOSE: Deep pressure input is used to normalize physiological arousal due to stress. Third molar extraction is an invasive dental procedure with high stress for the patient, and an alleviation strategy is rarely applied during tooth extraction. In the present study, we investigated the effects of deep pressure input on autonomic responses during the procedures of third molar extraction in healthy adolescents. METHODS: A randomized controlled crossover design was used for adolescents who were allocated to experimental and control groups that received intervention with or without deep pressure input, respectively. Autonomic indicators, namely the heart rate, percentage of low-frequency heart rate variability (LF-HRV), percentage of high-frequency heart rate variability (HF-HRV), and low-frequency/high-frequency heart rate variability ratio (LF/HF-HRV), were assessed at the baseline, during molar extraction, and in the posttreatment phase. RESULTS: The results indicated that third molar extraction caused significant autonomic parameter changes in both groups; however, differential response patterns were observed between two groups. In particular, application of deep pressure input in the experimental group was associated with higher HF-HRV and lower LF/HF-HRV during third molar extraction compared with those in the control group. CONCLUSION: LF/HF-HRV measurement revealed balanced sympathovagal activation in response to deep pressure application. The present study suggests that the application of deep pressure alters the response of HF-HRV and facilitate maintaining sympathovagal balance during third molar extraction.

Significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia in oral precancer patients.

BACKGROUND/PURPOSE: Our previous studies found relatively higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with different types of oral mucosal diseases. This study evaluated whether patients with oral precancerous lesions (oral precancer patients) had significantly higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels 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 were measured and compared. RESULTS: We found significantly lower mean serum iron (for women only), vitamin B12, and folic acid levels and a significantly higher mean serum homocysteine level in oral precancer patients than in healthy control subjects (all P-values < 0.05). Moreover, 131 oral precancer patients had significantly higher frequencies of blood hemoglobin (3.1%), vitamin B12 (43.5%), and folic acid (46.6%) deficiencies and hyperhomocysteinemia (22.1%) than 131 healthy control subjects (all P-values < 0.05). Of 131 oral precancer patients, lower mean serum folic acid levels were found in 87 cigarette smokers than in 44 non-smokers (P = 0.002), in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.024), and in 52 betel quid chewers than in 79 non-chewers (P = 0.051). CONCLUSION: There are significantly higher frequencies of anemia, serum vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in oral precancer patients than in healthy control subjects.

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.

Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumorigenesis.

Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (LDHA) or acetyl-CoA by Pyruvate Dehydrogenase E1 component α subunit (PDHA1) catalytic complex. In tumor cells, accumulating lactate is produced whereas the conversion of pyruvate into mitochondrial acetyl-CoA is less active compared with their normal counterparts. This reciprocal molecular association makes pyruvate metabolism a potential choice of anti-cancer target. Cellular and molecular changes were herein assayed in Head and Neck Squamous Cell Carcinoma (HNSCC) cells in response to LDHA and PDHA1 loss in vitro, in vivo and in clinic. By using various human cancer databases and clinical samples, LDHA and PDHA1 levels exhibit reversed prognostic roles. In vitro analysis demonstrated that decreased cell growth and motility accompanied by an increased sensitivity to chemotherapeutic agents was found in cells with LDHA loss whereas PDHA1-silencing exhibited opposite phenotypes. At the molecular level, it was found that oncogenic Protein kinase B (PKB/Akt) and Extracellular signal-regulated kinase (ERK) singling pathways contribute to pyruvate metabolism mediated HNSCC cell growth. Furthermore, LDHA/PDHA1 changes in HNSCC cells resulted in a broad metabolic reprogramming while intracellular molecules including polyunsaturated fatty acids and nitrogen metabolism related metabolites underlie the malignant changes. Collectively, our findings reveal the significance of pyruvate metabolic fates in modulating HNSCC tumorigenesis and highlight the impact of metabolic plasticity in HNSCC cells.

Safety and efficacy of computed tomography-guided dye localization using patent blue V for single lung nodule for video-assisted thoracoscopic surgery: a retrospective study.

BACKGROUND: For invisible or impalpable lung nodules, video-assisted thoracoscopic surgery (VATS) has some limitations; some preoperative localization has been developed to overcome this limitation. This study aimed to assess the safety and efficacy of preoperative computed tomography (CT)-guided localization with patent blue V dye. METHODS: In this retrospective study, we examined patients with solitary pulmonary nodule undergoing preoperative CT-guided patent blue V dye localization from 2013 to 2015. We analyzed patients' demographic data, nodular features, and procedures undergone. RESULTS: We enrolled 282 patients (282 lung nodules; mean age: 56.6±11.6 years, with female preponderance) in this study. The mean size of nodules was 0.9±0.5 cm, and mean time of localization was 24 min. The leading complications after localization were asymptomatic pneumothorax (48 patients, 17%) and localized pulmonary hemorrhage (51 patients, 18%). Other rare complications included subcutaneous emphysema and hematoma. We noted two cases with intraoperative poor or fail dye localization. Most patients underwent wedge resection (221 patients, 78.4%) and segmentectomy (36 patients, 12.8%), whereas 25 patients underwent lobectomy (8.9%) after the intraoperative frozen histopathological study confirmed malignancy. Furthermore, postoperative hospital stay was 4.8±2.0 days. Few patients experienced postoperative complications such as empyema (n=1), air leakage (n=3), and chylothorax (n=1). CONCLUSIONS: This study establishes that CT-guided dye localization is a safe and efficient method with rare severe complications and high success rate.

Gastric parietal cell and thyroid autoantibodies in recurrent aphthous stomatitis patients with concomitant oral lichen planus.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) have not yet been reported in recurrent aphthous stomatitis (RAS) patients with concomitant oral lichen planus (OLP/RAS patients). This study mainly assessed the frequencies of serum GPCA, TGA, and TMA (GPCA/TGA/TMA) positivities in 44 OLP/RAS patients. METHODS: The frequencies of serum GPCA/TGA/TMA positivities in 44 OLP/RAS patients, OLP/RAS patients of four different subgroups, 520 RAS patients, and 352 healthy control subjects were calculated and compared. RESULTS: We found that 20.5%, 27.3%, and 31.8% of 44 OLP/RAS patients, 75.0%, 100.0%, and 100.0% of 4 OLP/major-typed RAS (OLP/major RAS) patients, 15.0%, 20.0%, and 25.0% of 40 OLP/minor-typed RAS (OLP/minor RAS) patients, 45.5%, 72.7%, and 54.5% of 11 atrophic glossitis-positive OLP/RAS (AG+OLP/RAS) patients, and 12.1%, 12.1%, and 24.2% of 33 AG-negative OLP/RAS (AGÖ¾OLP/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. OLP/RAS patients and OLP/RAS patients of four different subgroups all had significantly higher frequencies of GPCA/TGA/TMA positivities than healthy control subjects. Moreover, OLP/RAS patients had a significantly higher frequency of TMA positivity than RAS patients, and OLP/major RAS and AG+OLP/RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than RAS patients. Furthermore, OLP/major RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than OLP/minor RAS patients. CONCLUSION: For OLP/RAS patients, the concomitant OLP may play a role in causing an increased frequency of TMA positivity, and major RAS and the concomitant AG are contributory factors causing the elevated frequencies of GPCA/TGA/TMA positivities.

Gastric parietal cell and thyroid autoantibodies in Behcet's disease patients with or without atrophic glossitis.

BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study mainly assessed the frequencies of serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 30 AG-positive RAS/BD (AG+RAS/BD) and 33 AG-negative RAS/BD (AGÖ¾RAS/BD) patients. METHODS: The frequencies of serum GPCA, TGA, and TMA positivities in 30 AG+RAS/BD patients, 33 AGÖ¾RAS/BD patients, and 126 healthy control subjects were calculated and compared. RESULTS: We found that 20.0%, 30.0%, and 26.7% of 30 AG+RAS/BD patients, 9.1%, 12.1%, and 15.2% of 33 AGÖ¾RAS/BD patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subject had the presence of GPCA, TGA, and TMA in their sera, respectively. The 30 AG+RAS/BD patients had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.001). The 33 AGÖ¾RAS/BD patients had a higher frequency of serum TGA positivity (P = 0.051, marginal significance) and a significantly higher frequency of serum TMA positivity (P = 0.011) than healthy control subjects. Although the 30 AG+RAS/BD patients had higher frequencies of serum GPCA, TGA, and TMA positivities than the 33 AGÖ¾RAS/BD patients, the differences were not significant. CONCLUSION: AG+RAS/BD patients do have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects. This finding indicates that the concomitant presence of AG may result in significantly elevated frequencies of serum GPCA, TGA, and TMA positivities in BD patients.

Gastric parietal cell and thyroid autoantibodies in patients with Behcet's disease.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) were rarely examined in Behcet's disease (BD) patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients. METHODS: The frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients, 19 major-typed recurrent aphthous stomatitis (RAS)/BD (major RAS/BD) patients, 44 minor-typed RAS/BD (minor RAS/BD) patients, 520 RAS patients, and 126 healthy control subjects were calculated and compared. RESULTS: We found that 14.3%, 20.6%, and 20.6% of 63 BD patients, 21.1%, 21.1%, and 26.3% of 19 major RAS/BD patients, 11.4%, 20.5%, and 18.2% of 44 minor RAS/BD patients, 11.5%, 18.5%, and 18.3% of 520 RAS patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subjects had serum GPCA, TGA, and TMA positivities, respectively. BD, major RAS/BD, minor RAS/BD, and RAS patients all had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.05). However, there were no significant differences in different serum autoantibody frequencies between BD, major RAS/BD, or minor RAS/BD patients and RAS patients. Of 16 TGA/TMA-positive BD patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.5%, 6.3%, and 6.3% of these TGA/TMA-positive BD patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 35% BD patients have serum GPCA/TGA/TMA positivity. However, BD patients do not have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than RAS patients.

Hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia in Behcet's disease patients with atrophic glossitis.

BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study mainly assessed whether 30 AG-positive RAS/BD (AG+RAS/BD) patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than 33 AG-negative RAS/BD (AGÖ¾RAS/BD) patients or 126 age- and sex-matched healthy control subjects. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations were measured and compared among 30 AG+RAS/BD patients, 33 AGÖ¾RAS/BD patients, and 126 healthy control subjects. RESULTS: We found that 43.3%, 33.3%, 13.3%, 6.7%, and 20.0% of 30 AG+RAS/BD patients and 18.2%, 36.4%, 0%, 6.1%, and 9.1% of 33 AGÖ¾RAS/BD patients had hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia, respectively. Moreover, 30 AG+RAS/BD patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than healthy control subjects (all P-values < 0.05), and had a higher frequency of hemoglobin deficiency (P = 0.058, marginal significance) and a significantly higher frequency of vitamin B12 deficiency (P = 0.046) than 33 AGÖ¾RAS/BD patients. In addition, the 33 AGÖ¾RAS/BD patients had significantly higher frequencies of hemoglobin and iron deficiencies than healthy control subjects (both P-values < 0.001). CONCLUSION: We conclude that AG+RAS/BD patients do have significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than healthy control subjects and have significantly higher frequencies of hemoglobin and vitamin B12 deficiencies than AGÖ¾RAS/BD patients.