Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images.

EGFR mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability. In this study, we developed a deep learning model to predict the presence of EGFR mutations by analyzing histopathological patterns in whole slide images (WSIs). We also introduced the EGFR mutation prevalence (EMP) score, which quantifies EGFR prevalence in WSIs based on patch-level predictions, and evaluated its interpretability and utility. Our model estimates the probability of EGFR prevalence in each patch by partitioning the WSI based on multiple-instance learning and predicts the presence of EGFR mutations at the slide level. We utilized a patch-masking scheduler training strategy to enable the model to learn various histopathological patterns of EGFR. This study included 868 WSI samples from lung adenocarcinoma patients collected from three medical institutions: Hallym University Medical Center, Inha University Hospital, and Chungnam National University Hospital. For the test dataset, 197 WSIs were collected from Ajou University Medical Center to evaluate the presence of EGFR mutations. Our model demonstrated prediction performance with an area under the receiver operating characteristic curve of 0.7680 (0.7607-0.7720) and an area under the precision-recall curve of 0.8391 (0.8326-0.8430). The EMP score showed Spearman correlation coefficients of 0.4705 (p = 0.0087) for p.L858R and 0.5918 (p = 0.0037) for exon 19 deletions in 64 samples subjected to next-generation sequencing analysis. Additionally, high EMP scores were associated with papillary and acinar patterns (p = 0.0038 and p = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (p = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.

The Analysis of Neutrophil to Lymphocyte Ratio (NLR), Lymphocyte to Monocyte Ratio (LMR), and Platelet to Lymphocyte Ratio (PLR) in Patients with Adenoidectomy and Tonsillectomy.

Background/Objectives: Adenoidectomy and tonsillectomy are among the most commonly performed procedures in ENT practice. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are recognized inflammatory markers. This study aims to evaluate the changes in NLR, PLR, and LMR in patients undergoing adenoidectomy and tonsillectomy. Methods: The study group consisted of 980 patients who underwent adenoidectomy and/or tonsillectomy. Preoperative and postoperative inflammatory markers were measured in all patients. The NLR, LMR, and PLR values were then calculated and analyzed. Results: In patients undergoing adenoidectomy and/or tonsillectomy, the postoperative NLR was significantly lower than the preoperative NLR. Similarly, the postoperative LMR was significantly higher, and the postoperative PLR was significantly lower compared to their preoperative values. Conclusions: The significant changes in NLR, LMR, and PLR following adenoidectomy and/or tonsillectomy suggest a reduction in systemic inflammation post-surgery. These findings indicate that these procedures may contribute to the improvement of inflammatory status in patients, highlighting the potential role of these markers in monitoring surgical outcomes.

Development of a multi-modal learning-based lymph node metastasis prediction model for lung cancer.

PURPOSE: This study proposed a three-dimensional (3D) multi-modal learning-based model for the automated prediction and classification of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT) images and clinical information. METHODS: We utilized clinical information and CT image data from 4239 patients with NSCLC across multiple institutions. Four deep learning algorithm-based multi-modal models were constructed and evaluated for lymph node classification. To further enhance classification performance, a soft-voting ensemble technique was applied to integrate the outcomes of multiple multi-modal models. RESULTS: A comparison of the classification performance revealed that the multi-modal model, which integrated CT images and clinical information, outperformed the single-modal models. Among the four multi-modal models, the Xception model demonstrated the highest classification performance, with an area under the curve (AUC) of 0.756 for the internal test dataset and 0.736 for the external validation dataset. The ensemble model (SEResNet50_DenseNet121_Xception) exhibited even better performance, with an AUC of 0.762 for the internal test dataset and 0.751 for the external validation dataset, surpassing the multi-modal model's performance. CONCLUSIONS: Integrating CT images and clinical information improved the performance of the lymph node metastasis prediction models in patients with NSCLC. The proposed 3D multi-modal lymph node prediction model can serve as an auxiliary tool for evaluating lymph node metastasis in patients with non-pretreated NSCLC, aiding in patient screening and treatment planning.

Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial.

PURPOSE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

Deep learning-radiomics integrated noninvasive detection of epidermal growth factor receptor mutations in non-small cell lung cancer patients.

This study focused on a novel strategy that combines deep learning and radiomics to predict epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT). A total of 1280 patients with NSCLC who underwent contrast-enhanced CT scans and EGFR mutation testing before treatment were selected for the final study. Regions of interest were segmented from the CT images to extract radiomics features and obtain tumor images. These tumor images were input into a convolutional neural network model to extract 512 image features, which were combined with radiographic features and clinical data to predict the EGFR mutation. The generalization performance of the model was evaluated using external institutional data. The internal and external datasets contained 324 and 130 EGFR mutants, respectively. Sex, height, weight, smoking history, and clinical stage were significantly different between the EGFR-mutant patient groups. The EGFR mutations were predicted by combining the radiomics and clinical features, and an external validation dataset yielded an area under the curve (AUC) value of 0.7038. The model utilized 1280 tumor images, radiomics features, and clinical characteristics as input data and exhibited an AUC of approximately 0.81 and 0.78 during the primary cohort and external validation, respectively. These results indicate the feasibility of integrating radiomics analysis with deep learning for predicting EGFR mutations. CT-image-based genetic testing is a simple EGFR mutation prediction method, which can improve the prognosis of NSCLC patients and help establish personalized treatment strategies.

Clinical outcome of rim-plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole.

Despite the variety of treatment methods, comminuted inferior pole fractures of the patella remain difficult and technically demanding to achieve stable internal fixation. The purpose of this study is to evaluate the clinical outcomes of rim plate-augmented separate vertical wiring with supplementary fixation in the management of comminuted inferior pole fractures, AO/OTA 34-A1, C2, and C3, which has the secondary horizontal fracture line on lower articular boundary. From our study, bony union was achieved in all patients at an average of 3.1 ± 1.4 months after surgery. There was no patient with loss of reduction, fixation failure, or infection during follow-up. The average final range of motion was 131.6° ± 7.2°. Lysholm knee scores gradually increased over 3, 6, 9, and 12 months postoperatively by 58.7, 74.0, 82.9, and 89.4, respectively. Isokinetic peak torque deficit of the knee extensor muscles in 3, 6, 9, and 12 months postoperatively was 59.9%, 49.7%, 35.7%, and 28.1%, respectively. The rim plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole is effective and can be safely applied AO/OTA 34-C2 or C3 with favorable outcomes.

Radiographic rotational profiles of the proximal and distal humerus: analysis of 46 computed tomography scans with 3-dimensional simulation.

BACKGROUND: To date, no study has investigated the radiographic rotational profiles (RRPs) of the proximal and distal humerus. However, malrotation after minimally invasive surgery for humeral fracture has been an unsolved problem. Therefore, we aimed to investigate the RRPs of the proximal and distal humerus that linearly correlate with rotational status and show significant differences as the rotational status changes. METHODS: Forty-six computed tomography scans of the humerus were 3-dimensionally reconstructed, and 5 rotational statuses (20° and 10° of internal rotation; neutral; and 10° and 20° of external rotation) were simulated. Seven candidate RRPs of the proximal humerus and 4 candidates of the distal humerus were measured for each rotational status. The overall differences and trends in the RRPs as the rotational status changed were evaluated, and multiple comparisons were performed between the RRPs for each of the 5 rotational statuses. Moreover, the correlations between the RRPs and rotational status with adjustment of retroversion were analyzed. Finally, interobserver and intraobserver reliabilities were evaluated. RESULTS: The following proximal and distal RRPs were linearly correlated with rotational status, differed significantly between the rotational statuses, and showed a relatively low prediction error and excellent interobserver and intraobserver reliabilities: the distance from the tip of the lesser tuberosity to the lateral margin of the proximal humerus (PL1) and the medial margin of the head (PL2), as well as the PL1 to PL2 ratio (PRL), in the proximal humerus; and the distance from the medial margin of the olecranon process to the medial epicondyle (DOP), the widest width of the overlapped olecranon fossa (DOF), and the distance from the lateral margin of the capitellum to the lateral epicondyle (DC) in the distal humerus. CONCLUSION: Our findings suggest that PL1, PL2, and PRL in the proximal humerus and DOP, DOF, and DC in the distal humerus are potentially useful and reproducible RRPs for restoring the intrinsic rotational alignment in humeral fractures.

Efficacy of crizotinib retreatment after crizotinib-related interstitial lung disease in a patient with ROS1-rearranged advanced lung adenocarcinoma: A case report and potential crizotinib retreatment strategy.

Crizotinib is an oral selective small-molecular tyrosine kinase inhibitor (TKI) that suppress the activity of anaplastic lymphoma kinase (ALK) and ROS1 kinases, as well as mesenchymal-epithelial transition. The cumulative clinical trials in patients with advanced ALK- or ROS1-rearrangement NSCLC indicate that crizotinib has significant antitumor activity and a tolerable safety profile, with mild or moderate adverse events of visual disorders, diarrhea, nausea, and vomiting. As with other TKIs, however, the occurrence of crizotinib-related interstitial lung disease (crizotinib-ILD) remains a major clinical dilemma that can lead to the permanent discontinuation of TKI during cancer treatment. When there is no suitable alternative therapy for patients who develop crizotinib-ILD, some clinicians have reported successful crizotinib retreatment in cases of ALK-rearrangement NSCLC. Unfortunately, there are no specific guidelines for the treatment or retreatment of TKI-related ILD. We herein report the first successful crizotinib retreatment after crizotinib-ILD in a patient with ROS1-rearranged NSCLC, and suggest a retreatment strategy after crizotinib-ILD based on a literature review.

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage.

Introduction: Salivary gland (SG) damage is commonly caused by aging, irradiation, and some medications, and currently, no damage modifying agent is available. However, cell therapy based on mesenchymal stem cells (MSCs) has been proposed as a therapeutic modality for irradiated SGs. Therefore, we administered cell-derived vesicles (CDVs) of adipose-derived mesenchymal stem cells (ADMSCs) to irradiated SG cells to investigate their radioprotective effects in vitro. Methods: The artificial CDVs were obtained from ADMSC by tangential flow filtration (TFF) purification and ultracentrifugation. Cultured human SG epithelial cells were exposed to 2, 5 or 15 Gy of 4 MV X-rays produced by a linear accelerator. The effects of ADMSC-CDVs on SG epithelial cells damaged by irradiation were tested by proliferation activity, transepithelial electrical resistance (TEER), and amylase activity. Results: Exposure to penetrating radiation inhibited the proliferation of SG epithelial cells, but the radiation intensity required to reduce the proliferation of human submandibular gland epithelial cells (hSMGECs) was greater than required for other SG cells. ADMSC-CDVs restored the proliferative ability of SG epithelial cells reduced by irradiation, and the proliferation capacities of irradiated human parotid gland epithelial cells (hPGECs) and human sublingual gland epithelial cells (hSLGECs) were increased by administering ADMSC-CDVs to non-irradiated SG epithelial cells. Furthermore, amylase activity in irradiated hPGECs, hSMGECs, and hSLGECs was lower than in non-irradiated controls. However, amylase ability was restored in all by ADMSC-CDV treatment. Also, TEER was diminished by irradiation in hPGECs, hSMGECs, and hSLGECs and restored by ADMSC-CDV administration. Conclusion: Overall, our findings demonstrate that ADMSC-CDVs have potent radioprotective effects on irradiated SG cells.

Femoral matched tibia component rotation has little effect on the tibial torsion after total knee arthroplasty.

PURPOSE: Tibiofemoral synchronization technique matches the rotational alignment of the tibial component to the femoral component during the total knee arthroplasty (TKA). The rotational axis of the proximal tibia can be changed by this technique, which affects tibial torsion postoperatively. The purpose of this study was to investigate whether the tibiofemoral synchronization technique affect the tibial torsion, and the lower limb rotation after primary TKA. It was hypothesised that the tibial torsion would change after primary TKA. METHODS: Ninety-three posterior stabilised TKAs from 89 patients were included from January 2017 to December 2018. Mechanical hip-knee-ankle axis (mHKA), in plain radiographs, femoral anteversion, tibial torsion, femoral neck-malleolar angle (FNMA), and rotational alignment of the femoral and the tibial components in pre- and postoperative CT scans were measured by two blinded observers. The primary outcome was a postoperative change in femoral anteversion, tibial torsion and FNMA. Clinical outcomes were evaluated using the American Knee Society Knee Score (AKSKS)/Function Score (AKSFS), and Oxford Knee Score (OKS) preoperatively and at 1 year after TKA. Patients' perception of changes in the foot progression angle after TKA was investigated. Statistical significance was set at p < 0.05. RESULTS: The mean rotational mismatch between the femoral and the tibial component was 0.6 ± 3.2°. There was a significant decrease in femoral anteversion (9.5 ± 6.7° vs. 5.2 ± 6.6°, p < 0.001), and a significant increase in the FNMA (17.6 ± 9.7° vs. 21.8 ± 10.5°, p = 0.005) after TKA, while no significant change in tibia torsion was observed (25.4 ± 8.8° vs. 24.9 ± 9.3°, p = 0.739). AKSS (37.8 ± 15.1 vs. 92.8 ± 8.8, p < 0.001), AKSFS (53.9 ± 18.1 vs. 89.9 ± 5.3, p < 0.001), and OKS (18.0 ± 7.3 vs. 39.9 ± 4.8, p < 0.001) were significantly improved at 1 year after TKA. Ten knees (11%) had changes in tibial torsion greater than ± 10° postoperatively. Four of five patients who had changes in FNMA greater than 15° perceived the external rotation of the foot progression angle after TKA. All four patients had an increase in tibial torsion larger than 10°. CONCLUSION: Our study shows that the tibiofemoral synchronization technique less likely affects the tibial torsion after primary TKA.

Influence of carpal-ulnar translation on clinical outcome after scaphocapitate arthrodesis for the treatment of late-stage Kienböck disease.

BACKGROUND: This study sought to compare postoperative outcomes after scaphocapitate arthrodesis (SCA) for the treatment of late-stage Kienböck disease according to the amount of ulnar translation of the carpus and to identify surgical factors associated with carpal-ulnar translation. METHODS: Thirty-nine patients diagnosed with Kienböck disease (Lichtman stages III-IV) and treated with SCA were retrospectively reviewed. They were divided into the translated group (n=28) and untranslated group (n=11) according to the presence of carpal-ulnar translation. The following surgical factors in the patients were assessed: excision of the lunate, postoperative carpal height ratio, and radioscaphoid angle (RSA). Pain Visual Analog scale (VAS) score, wrist range of motion, grip strength, modified Mayo wrist score (MMWS), the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and progression of radioscaphoid osteoarthritis were also assessed. RESULTS: All patients showed functional improvement after a mean postoperative follow-up period of 40 months (VAS: 4.1 vs. 1.1, p <0.001; grip strength, 42.3 vs. 51.2 lb., p = 0.002; MMWS, 52.6 vs. 69.5, p <0.001; QuickDASH, 33.7 vs. 21.5, p <0.001). No statistically significant differences were found between the two groups in terms of outcome measures. Among the assessed surgical factors, the mean postoperative RSA was significantly smaller in the translated group than in the untranslated group (34.8° vs. 46.8°, p = 0.008). The proportion of patients with postoperative RSA <30° was significantly higher in the translated group than in the untranslated group (54.5% vs. 0%, p<0.001). CONCLUSION: These results suggest that sufficient pain relief and functional improvement can be achieved after SCA for the treatment of late-stage Kienböck disease disregarding the occurrence of carpal-ulnar translation. In this study, overcorrection to RSA <30° induced more frequent carpal-ulnar translation after SCA.

Pediatric schwannoma of the tongue: A case report and review of literature.

BACKGROUND: Neurogenic tumors account for about ten percent of all tumors of childhood, and benign tumor originating from Schwann cells is rare in peripheral nerves. Schwannoma of the tongue is quite rare in children. CASE SUMMARY: We present the case of an 8-year-old male with schwannoma in the anterolateral tongue. The mass was slow-growing for one year with no pain and discomfort. He underwent transoral mass excision under general anesthesia. Gross examination revealed a smooth surfaced, 17 mm × 14 mm × 7 mm sized, encapsulated nodule with a clear resection margin. Schwannoma of the tongue was confirmed by the pathological exam. He reported no motor or sensory change, such as dysgeusia or paresthesia, or phonation difficulty during postoperative 12 mo follow-up. CONCLUSION: Schwannoma of the tongue is a rare benign neoplasm in childhood. If a painless firm mass is encountered in the tongue of a child, solid tumors like schwannoma should be considered in the differential diagnosis.

Intralesional platelet-rich plasma injection promotes tongue regeneration following partial glossectomy in a murine model.

BACKGROUND: We examined the regenerative efficacy of the activated platelet-rich plasma (PRP) concentrate administered by local injection in an animal model mimicking partial glossectomy for tongue cancer. METHODS: Four-week-old mice were randomized to four groups; (1) a treatment-naïve control group, (2) a PRP group, (3) a hemiglossectomy group, and (4) a hemiglossectomy + PRP group. The activated PRP concentrate was injected into the deep layer of resected surfaces of mouse tongues immediately after excision, and tongue widths and lengths were measured on postoperative days (POD) 5 and 12. Gross tongue morphologies and microscopic findings were investigated. Inflammation and fibrous tissue areas were also measured, and immunohistochemical analysis was performed for c-kit, neurofilament, and S-100. RESULTS: The activated PRP concentrate reduced wound scar contracture, promoted wound healing, and reduced inflammation and wound fibrosis. On POD 12, histologic findings in the hemiglossectomy + PRP group were similar to those in the normal control group, and the intensity of stem cell factor receptor c-kit expression was also significantly greater in the PRP group than in the hemiglossectomy group on POD 12. Immunohistochemical staining revealed S100 and neurofilament expressions in the hemiglossectomy + PRP group were significantly more intense than in the hemiglossectomy group. CONCLUSION: Intralesional activated PRP concentrate injection has potential use for tongue regeneration, wound healing, and neural regeneration with minimal scarring after partial glossectomy.

Keratinocyte Growth Factor-1 Protects Radioiodine-Induced Salivary Gland Dysfunction in Mice.

BACKGROUND: Most patients with thyroid cancer suffer from salivary gland (SG) dysfunctions after radioiodine (RI) therapy. We investigated the effects of keratinocyte growth factor (KGF)-1 on RI-induced SG dysfunction in an animal model. METHODS: Six C57BL/6 mice were assigned to each of the following groups: treatment naïve control group, RI group, and RI+KGF-1 group. Body and SG weights, salivary flow rates, salivary lag times and changes in 99mTc pertechnetate uptake and excretion were measured, and histologic changes were noted. Amylase activities and epidermal growth factor (EGF) concentrations in saliva were also measured. In addition, TUNEL assays were performed and apoptosis-related protein expressions were assessed. RESULTS: RI-induced reductions in salivary flow rates and increases in salivary lag times observed in the RI group were not observed in RI+KGF-1 group. Mice in RI group had higher HIF1a levels than controls, but HIF1a levels in RI+KGF-1 group were similar to those in control group. Furthermore, mice in RI+KGF-1 group had more mucin stained acini and decreased periductal fibrosis than mice in RI group, and tissue remodeling of many salivary epithelial cells (AQP5) and endothelial cells (CD31) were observed in RI+KGF-1 group. Amylase activity and expression in saliva were greater in RI+KGF-1 group than in RI group, and fewer apoptotic cells were observed in RI+KGF-1 group. Furthermore, BCLxl (anti-apoptotic) expression was higher, and Bax (pro-apoptotic) expression was lower in RI+KGF-1 group than in RI group. CONCLUSIONS: Local delivery of KGF-1 might prevent RI-induced SG damage by reducing apoptosis.

Does Salivary Function Decrease in Proportion to Radioiodine Dose?

OBJECTIVES: This study was conducted to investigate the dose-response characteristics of radioiodine on salivary glands and to investigate the mechanism responsible for radioiodine-induced salivary glands toxicity. METHODS: Twenty-four mice were divided into six groups: 0, 0.05, 0.10, 0.20, 0.40, and 0.80 mCi/20 g mouse, administered orally. Mortalities were noted 12 months after radioiodine administration. Body weights, gland weights, salivary lag times, flow rates, and changes in 99m Tc pertechnetate were recorded. Histopathological changes and mRNA expressions were also evaluated, and immunohistochemical analysis and apoptotic assays were performed. RESULTS: Survival rates, body weights, gland weights, and flow rates decreased, and lag times increased on increasing radioiodine dose. Animals administered radioiodine showed acinar atrophy, striated duct dilations, and lymphocytic infiltration in glands and irregular destruction of epithelial surfaces of tongue. The uptake and excretion of 99m Tc pertechnetate were impaired by radioiodine. Immunohistochemical analysis showed that numbers of salivary epithelial, myoepithelial, and endothelial cells decreased and that numbers of ductal cells increased with radioiodine dose. Oxidative stress biomarker levels increased; reactive oxygen species scavenger levels decreased; and numbers of apoptotic cells increased in animals exposed to higher radioiodine doses. CONCLUSION: These dose-related, long-term effects on salivary gland should be taken into account when determining radioiodine doses. LEVEL OF EVIDENCE: NA Laryngoscope, 130:2173-2178, 2020.

Identification of new genes of pleomorphic adenoma.

Pleomorphic adenoma is the most common salivary gland neoplasm with a variety of histologic appearances. Due to this diversity, precise preoperative diagnosis through fine needle aspiration cytology is difficult.This study sought to identify the differentially expressed genes in pleomorphic adenoma to aid precise diagnosis and clarify the mechanism of tumorigenesis.Suppressive subtractive hybridization was performed on pleomorphic adenoma tissues and the corresponding normal salivary gland tissues to screen of the differential expression of genes in pleomorphic adenoma.Four known genes (microfibrillar associated protein 4 [MFAP4], dystonin [DST], solute carrier family 35 [SLC35], and potassium channel tetramerization domain containing 15 [KCTD15]) were differentially expressed in the tumors compared with the genes in normal tissues. The expression profiles were further confirmed in 15 pleomorphic adenoma and corresponding normal salivary gland tissues by quantitative real-time reverse transcription-polymerase chain reaction.MFAP4, DST, SLC35, and KCTD15 gene expression could be potential biomarkers of pleomorphic adenoma for precise diagnosis.

Adipose-derived mesenchymal stem cells regenerate radioiodine-induced salivary gland damage in a murine model.

After radioiodine (RI) therapy, patients with thyroid cancer frequently suffer from painful salivary gland (SG) swelling, xerostomia, taste alterations, and oral infections. This study was aimed to determine whether adipose-derived mesenchymal stem cells (AdMSCs) might restore RI-induced SG dysfunction in a murine model. Forty -five mice were divided into three groups; a PBS sham group, a RI+ PBS sham group (0.01 mCi/g mouse, orally), and an RI+AdMSCs (1 × 105 cells/150 uL, intraglandular injection on experimental day 28) treated group. At 16 weeks after RI treatment, body weights, SG weight, salivary flow rates (SFRs), and salivary lag times were measured. Morphologic and histologic examinations and immunohistochemistry (IHC) were performed and the activities of amylase and EGF in saliva were also measured. Changes in salivary 99mTc pertechnetate excretion were followed by SPECT and TUNEL assays were performed. The body and SG weights were similar in the AdMSCs and sham groups. Hematoxylin and eosin staining revealed the AdMSCs group had more mucin-containing acini than the RI group. Furthermore, AdMSCs treatment resulted in tissue remodeling and elevated expressions of epithelial (AQP5) and endothelial (CD31) markers, and increased SFRs. The activities of amylase and EGF were higher in the AdMSCs group than in the RI treated group. 99mTc pertechnetate excretions were similar in the AdMSCs and sham group. Also, TUNEL positive apoptotic cell numbers were less in the AdMSCs group than in the RI group. Local delivery of AdMSCs might regenerate SG damage induced by RI.

Tongue base varix as a source of oral bleeding: A case report.

RATIONALE: Oral bleeding is usually diagnosed after by referral to other department for the differential diagnosis of hematemesis or hemoptysis. If a patient presents with blood in the oral cavity with no obvious source, generally upper airway, pulmonary, or gastroesophageal lesions are considered likely bleeding foci. The tongue base is an unusual site for laryngopharyngeal varices and only a few cases have been reported. PATIENT CONCERNS: Although varix at the tongue base in patients with liver cirrhosis has been rarely described, physicians must consider variceal bleeding from the tongue base when presented with oral bleeding. In such cases, bleeding foci can be identified and controlled by laryngoscopy. We describe the case of a 42-year-old woman complaining of small amount of hemoptysis with variceal bleeding at the tongue base controlled by laryngoscopic excision and cauterization. DIAGNOSIS: A diagnosis of tongue base varix was made based on medical history, clinical manifestations, laryngoscopic findings and pathologic features for the patient. INTERVENTIONS: The successful laryngoscopic procedures were performed. OUTCOMES: The patient has shown no recurrent oral bleeding during follow-up. LESSONS: Variceal bleeding in the tongue base is likely to cause serious massive hemorrhage. We need to consider this possibility when presented with a patient with intraoral bleeding but no evidence of hemoptysis or hematemesis.

Fucoidan attenuates radioiodine-induced salivary gland dysfunction in mice.

BACKGROUND: Radioiodine (RI) treatments can destroy the cellular components of salivary glands (SG) and disrupt their function. This study investigated whether fucoidan could attenuate radioiodine-induced SG dysfunction in a mouse model. METHODS: Female C57BL/6 mice (n = 36) were classified into three groups; i) a normal (control) group, ii) an RI-treated group (0.2 mCi/20 g mouse, administered orally), and iii) a fucoidan and RI-treated group. Mice in each group were classified into three subgroups and sacrificed at 2, 4, and 12 weeks after RI treatment. The measurements of salivary flow rates and lag times and histomorphologic examinations were performed, and apoptotic assays were conducted. Changes in salivary 99mTechnetium (Tc)-pertechnetate parameters using single-photon emission computed tomography were followed. RESULTS: Salivary flow rates and lag times in the fucoidan group were improved compared to the RI-treated group. Histologic examinations of SGs in the fucoidan group showed mucin-rich parenchymal areas and reduced periductal fibrosis as compared to the RI-treated group. Moreover, compared with the RI-treated group, fucoidan-treated groups showed evidence of cytoprotection, with a greater number of salivary epithelial cells and myoepithelial cells being observed. Fewer apoptotic cells were observed in the fucoidan group as compared to the RI group. The extent of 99mTc pertechnetate excretion in the fucoidan group was similar to that of the control group. CONCLUSION: Our results demonstrate that fucoidan administration before RI treatment could attenuate RI-induced SG damage and provides a possible candidate for preventing SG damage induced by RI.

Association between salivary secretary function and laryngopharyngeal reflux: a prospective study.

OBJECTIVES: This study aimed to demonstrate the prevalence and risk factors of laryngopharyngeal reflux (LPR) in patients with xerostomia and to investigate the association between salivary function and LPR. STUDY DESIGN: The prevalence of LPR among patients with xerostomia was analyzed and the clinical and salivary gland function were compared between 2 groups; the non-LPR and the LPR groups. RESULTS: The prevalence of LPR was 82.2% in patients with xerostomia. The presence of LPR was correlated with the unstimulated or stimulated salivary flow rate (SFR). LPR did not correlate with scintigraphy findings except time to the minimum count of the parotid gland. Low stimulated SFR and unstimulated SFR were recognized as independent risk factors of LPR. A significant correlation was observed between the Reflux Symptom Index and the xerostomia symptoms score. Furthermore, RFS also correlated with unstimulated and stimulated SFR. CONCLUSIONS: This finding supports that salivary secretory function has an impact on LPR.