Increased salivary microvesicles are associated with the prognosis of patients with oral squamous cell carcinoma.

Microvesicles (MVs), which are cell-derived membrane vesicles present in body fluids, are closely associated with the development of malignant tumours. Saliva, one of the most versatile body fluids, is an important source of MVs. However, the association between salivary MVs (SMVs) and oral squamous cell carcinoma (OSCC), which is directly immersed in the salivary milieu, remains unclear. SMVs from 65 patients with OSCC, 21 patients with oral ulcer (OU), and 42 healthy donors were purified, quantified and analysed for their correlations with the clinicopathologic features and prognosis of OSCC patients. The results showed that the level of SMVs was significantly elevated in patients with OSCC compared to healthy donors and OU patients. Meanwhile, the level of SMVs showed close correlations with the lymph node status, and the clinical stage of OSCC patients. Additionally, the ratio of apoptotic to non-apoptotic SMVs was significantly decreased in OSCC patients with higher pathological grade. Consistently, poorer overall survival was observed in patients with lower ratio of apoptotic to non-apoptotic SMVs. In conclusion, the elevated level of SMVs is associated with clinicopathologic features and decreased survival in patients with OSCC, suggesting that SMVs are a potential biomarker and/or regulator of the malignant progression of OSCC.

Treatment of Multiple Odontogenic Keratocysts Involving Chinese Patients.

PURPOSE: The optimal treatment of odontogenic keratocysts (OKCs) remains a matter of debate in reported studies. The present study aimed to estimate the postoperative recurrence rates of multiple OKCs (MOKCs) in Chinese patients. MATERIALS AND METHODS: A retrospective cohort study of histologically confirmed MOKCs treated from 2003 to 2017 using enucleation, marsupialization alone, enucleation and peripheral ostectomy, or marsupialization followed by secondary enucleation was performed. Patients with MOKCs who had undergone follow-up for 12 or more months with panoramic radiographs and radiographs of the chest and skull available from the first visit and had been treated by the same team using the same treatment protocol were included in the study. Patients were excluded if the lesion had been treated previously, they had a solitary OKC, or their medical records were not available for review. The treatment methods, recurrence rate, and interval to recurrence were evaluated. The Kaplan-Meier method was used to estimate the survival rate and median time to recurrence. Univariate analysis was used to identify the risk factors associated with recurrence. Significant differences were determined at an α level of 5%. RESULTS: The sample included 81 patients with MOKCs; 21 (25.6%) were male and 60 (74.07%) were female. The age range was 7 to 63 years (mean ± standard deviation, 18.4 ± 4). The overall recurrence rate was 26.63%, with an overall recurrence-free interval of 26.85 months. The average length of follow-up was 55.68 months. No association was found between the treatment method used and the risk of recurrence (P = .178). Although the interval to recurrence was not affected by any of the study variables, the average interval to the recurrence of MOKCs involving the maxilla was short compared with that of MOKCs involving the mandible. CONCLUSIONS: The surgical treatment method did not influence the risk of recurrence in patients with MOKCs, and the interval to recurrence was not associated with any of the study variables.

Overexpression of Fra-1, c-Jun and c-Fos in odontogenic keratocysts: potential correlation with proliferative and anti-apoptotic activity.

AIMS: The purpose of this study was to explore the potential involvement of Fra-1, c-Jun and c-Fos, three vital members of the AP-1 complex, in the pathogenesis of odontogenic keratocysts (OKCs). METHODS AND RESULTS: Tissue samples, containing 10 normal oral mucosa (OM), 10 dentigerous cysts (DC) and 32 OKC specimens, were applied to investigate the expression levels of Fra-1, c-Jun and c-Fos by immunohistochemistry and real-time-quantitative polymerase chain reaction (RT-qPCR). The association between Fra-1, c-Jun and c-Fos expression levels and markers of proliferation [Ki-67, proliferating cell nuclear antigen (PCNA)], anti-apoptosis (Bcl-2) was then investigated in the OKC serial tissue sections. The results showed that Fra-1, c-Jun and c-Fos expression levels were increased significantly in OKCs compared to these in OM and DC tissue samples. Meanwhile, the expression levels of Fra-1, c-Jun and c-Fos were associated positively with the expression levels of Ki-67, PCNA and Bcl-2, as confirmed further by double-labelling immunofluorescence analysis and hierarchical analysis. CONCLUSIONS: This study revealed for the first time that Fra-1, c-Jun and c-Fos were overexpressed in OKCs and had a close correlation with proliferation and anti-apoptosis potential of OKCs.

Osteoradionecrosis of the Zygoma.

Osteoradionecrosis occurs in 4.74% to 37.5% of patients following radiation therapy for head and neck cancer. Osteoradionecrosis mostly happens in the mandible but seldom occurs in other maxillofacial bones. Here, the authors reported a rare case of zygomatic osteoradionecrosis which occurred after maxillectomy and then radiotherapy because of maxillary myoepithelial carcinoma. After resection of zygoma sequestrum, the defect was repaired with forehead flap and healed uneventfully.

Ultrasmall Magnetically Engineered Ag2Se Quantum Dots for Instant Efficient Labeling and Whole-Body High-Resolution Multimodal Real-Time Tracking of Cell-Derived Microvesicles.

Cell-derived microvesicles (MVs) are natural carriers that can transport biological molecules between cells, which are expected to be promising delivery vehicles for therapeutic purposes. Strategies to label MVs are very important for investigation and application of MVs. Herein, ultrasmall Mn-magnetofunctionalized Ag2Se quantum dots (Ag2Se@Mn QDs) integrated with excellent near-infrared (NIR) fluorescence and magnetic resonance (MR) imaging capabilities have been developed for instant efficient labeling of MVs for their in vivo high-resolution dual-mode tracking. The Ag2Se@Mn QDs were fabricated by controlling the reaction of Mn(2+) with the Ag2Se nanocrystals having been pretreated in 80 °C NaOH solution, with an ultrasmall size of ca. 1.8 nm, water dispersibility, high NIR fluorescence quantum yield of 13.2%, and high longitudinal relaxivity of 12.87 mM(-1) s(-1) (almost four times that of the commercial contrast agent Gd-DTPA). The ultrasmall size of the Ag2Se@Mn QDs enables them to be directly and efficiently loaded into MVs by electroporation, instantly and reliably conferring both NIR fluorescence and MR traceability on MVs. Our method for labeling MVs of different origins is universal and free of unfavorable influence on intrinsic behaviors of MVs. The complementary imaging capabilities of the Ag2Se@Mn QDs have made the long-term noninvasive whole-body high-resolution dual-mode tracking of MVs in vivo realized, by which the dynamic biodistribution of MVs has been revealed in a real-time and in situ quantitative manner. This work not only opens a new window for labeling with QDs, but also facilitates greatly the investigation and application of MVs.

Down-regulation of connexin43 and connexin32 in keratocystic odontogenic tumours: potential association with clinical features.

AIMS: The objective of this study was to explore the potential involvement of connexin43 (Cx43) and connexin32 (Cx32), two vital members of the connexin families, in the pathogenesis of keratocystic odontogenic tumours (KCOT). METHODS AND RESULTS: The expression levels of Cx43 and Cx32 in human KCOT and normal oral mucosa (OM) tissues were measured using immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR). The relationship between Cx43 and Cx32 expression and markers of proliferation [proliferating cell nuclear antigen (PCNA), cyclin D1], anti-apoptosis [B cell lymphoma 2 (Bcl-2)] and autophagy [light chain 3 (LC3), Sequestosome 1 p62 (p62)] was then investigated in the KCOT samples. The results showed that Cx43 and Cx32 expression was down-regulated significantly in KCOT samples relative to OM samples. Meanwhile, the expression levels of Cx43 and Cx32 were correlated negatively with the expression levels of PCNA, cyclin D1, Bcl-2, LC3 and p62, as confirmed further by double-labelling immunofluorescence analyses. CONCLUSIONS: This study reveals for the first time that Cx43 and Cx32 are down-regulated in KCOT and suggests an association with growth regulation, anti-apoptosis and autophagy in KCOT.

Aneurysmal bone cysts of the jaws: analysis of 17 cases.

PURPOSE: Aneurysmal bone cysts (ABCs) are benign osteolytic lesions that occur relatively rarely in the jaws. The aim of the present study was to investigate the clinical and radiographic characteristics, pathologic features, and treatment results of ABCs of the jaws (JABCs). MATERIALS AND METHODS: A retrospective analysis of a 20-year database, including 17 cases of JABC, was performed. RESULTS: A total of 17 patients, 9 males and 8 females, aged 7 to 47 years (mean 20.4, median 14), were included. Of the 17 lesions, 15 (88.2%) were located in the mandible and 2 (11.8%) in the maxilla. A painless (12 of 17, 70.6%) or painful (3 of 17, 17.6%) swelling was the most common clinical finding. The pathologic analyses revealed that 13 JABCs (76.5%) were secondary in nature, including 11 cases associated with ossifying fibroma. Radiologically, the lesions frequently presented as multilocular (58.8%), well-defined (70.6%) radiolucencies (82.4%). Two lesions (11.8%) recurred. CONCLUSIONS: Our results suggest that most JABCs are secondary in nature and frequently associated with ossifying fibroma. The patients with JABCs presented with various clinical and radiographic features and therefore often posed a diagnostic dilemma. Resection is the preferred treatment of JABCs.

Effects of bleomycin on tooth eruption: a novel potential application.

There are many kinds of potentially undesirable teeth. At present, surgical extraction is the most efficient way to eliminate these teeth, but it's very complex and invasive. In this study, we investigated the effects of bleomycin (BLM) on dental follicle and tooth eruption as a potential conservative therapy for undesirable teeth. Our data showed that local injection of 0.2 U/kg BLM had no significant effects on tooth eruption compared to the control group in Wistar rats. With higher dose of BLM (0.5 or 2 U/kg), the eruption of treated teeth was interrupted and their root formation failed until 4 weeks postnatal without significant systemic toxicity. Additionally, those effects were not depending on the toxicity of overdose evidenced by TUNEL assay. In summary, injecting BLM into dental follicle at an early stage could interrupt tooth development and eruption, and may prevent the potentially clinical problems resulting from undesirable teeth instead of surgical removal.

A deep learning algorithm for detection of oral cavity squamous cell carcinoma from photographic images: A retrospective study.

BACKGROUND: The overall prognosis of oral cancer remains poor because over half of patients are diagnosed at advanced-stages. Previously reported screening and earlier detection methods for oral cancer still largely rely on health workers' clinical experience and as yet there is no established method. We aimed to develop a rapid, non-invasive, cost-effective, and easy-to-use deep learning approach for identifying oral cavity squamous cell carcinoma (OCSCC) patients using photographic images. METHODS: We developed an automated deep learning algorithm using cascaded convolutional neural networks to detect OCSCC from photographic images. We included all biopsy-proven OCSCC photographs and normal controls of 44,409 clinical images collected from 11 hospitals around China between April 12, 2006, and Nov 25, 2019. We trained the algorithm on a randomly selected part of this dataset (development dataset) and used the rest for testing (internal validation dataset). Additionally, we curated an external validation dataset comprising clinical photographs from six representative journals in the field of dentistry and oral surgery. We also compared the performance of the algorithm with that of seven oral cancer specialists on a clinical validation dataset. We used the pathological reports as gold standard for OCSCC identification. We evaluated the algorithm performance on the internal, external, and clinical validation datasets by calculating the area under the receiver operating characteristic curves (AUCs), accuracy, sensitivity, and specificity with two-sided 95% CIs. FINDINGS: 1469 intraoral photographic images were used to validate our approach. The deep learning algorithm achieved an AUC of 0·983 (95% CI 0·973-0·991), sensitivity of 94·9% (0·915-0·978), and specificity of 88·7% (0·845-0·926) on the internal validation dataset (n = 401), and an AUC of 0·935 (0·910-0·957), sensitivity of 89·6% (0·847-0·942) and specificity of 80·6% (0·757-0·853) on the external validation dataset (n = 402). For a secondary analysis on the internal validation dataset, the algorithm presented an AUC of 0·995 (0·988-0·999), sensitivity of 97·4% (0·932-1·000) and specificity of 93·5% (0·882-0·979) in detecting early-stage OCSCC. On the clinical validation dataset (n = 666), our algorithm achieved comparable performance to that of the average oral cancer expert in terms of accuracy (92·3% [0·902-0·943] vs 92.4% [0·912-0·936]), sensitivity (91·0% [0·879-0·941] vs 91·7% [0·898-0·934]), and specificity (93·5% [0·909-0·960] vs 93·1% [0·914-0·948]). The algorithm also achieved significantly better performance than that of the average medical student (accuracy of 87·0% [0·855-0·885], sensitivity of 83·1% [0·807-0·854], and specificity of 90·7% [0·889-0·924]) and the average non-medical student (accuracy of 77·2% [0·757-0·787], sensitivity of 76·6% [0·743-0·788], and specificity of 77·9% [0·759-0·797]). INTERPRETATION: Automated detection of OCSCC by deep-learning-powered algorithm is a rapid, non-invasive, low-cost, and convenient method, which yielded comparable performance to that of human specialists and has the potential to be used as a clinical tool for fast screening, earlier detection, and therapeutic efficacy assessment of the cancer.

Teratoid cyst of floor of the mouth: a clinicopathologic study of 20 Chinese patients.

The aim of this study is to document the clinicopathologic features of teratoid cyst of the floor of the mouth in 20 Chinese patients, who were treated in Wuhan University. The 20 teratoid cysts were analyzed. All cases were confirmed by pathology. English literature was also reviewed. Our investigations showed that both sexes were equal to have these cysts. The age at diagnosis ranged from 25 days to 34 years, and the greatest frequency was within the first decade. It was found that the congenital cysts were most commonly diagnosed in the midline. All cases were treated by cystectomy, using 1 of the 2 approaches: extraoral or intraoral. Whenever, combined approaches were used in 2 cases. In all, 16 patients were followed-up, and 2 patients had recurrences. The intraoral approach was also effective for the treatment of large lesions and led to very good cosmetic and functional results.