Clinicopathological evaluation of oral leukoplakia: a single-center study of 676 cases in Japan.

OBJECTIVES: To analyze the clinical and histopathological characteristics of oral leukoplakia (OL) in the Japanese population and investigate the prevalence and risk factors for epithelial dysplasia (ED) and carcinoma within lesions. STUDY DESIGN: Data, including age, sex, lesion site, and histopathological features, of 676 cases diagnosed with OL over the previous 10 years were analyzed. Dysplasia and carcinoma prevalence were determined. RESULTS: In male patients, the most affected site was the gingiva (42.7%), whereas in females, it was the tongue (47.6%). Moreover, ED was more prevalent in males (41.9%), whereas epithelial hyperplasia was more common in females (44.7%). A significant difference was observed between affected sites with regard to the presence of dysplasia. The ED rates by site were 64.6% and 33.7% for the tongue and gingiva, respectively (P < 0.05). The squamous cell carcinoma rates by site were 23.4%, 5.4%, and 3.4% for the tongue, buccal mucosa, and gingiva, respectively (P < 0.05). Logistic regression analysis revealed a higher prevalence of dysplasia in males than it did in females and that the risk for both dysplasia and carcinoma was highest in the tongue. CONCLUSIONS: Dysplasia is common in OL cases, often showing carcinoma. Early biopsy and interventions are key in OL management.

Impact of skeletal muscle mass on postoperative complications in oral cancer surgery.

BACKGROUND: Sarcopenia is characterized by a progressive and generalized loss of skeletal muscle mass and strength. The aim of this retrospective study was to investigate the impact of skeletal muscle mass on adverse events in free-flap reconstruction for defects after oral cancer resection. RESULTS: Of 120 patients, recipient-site adverse events occurred in 56 patients (46.7%), and recipient-site surgical site infections occurred in 45 patients (37.5%). Skeletal muscle index was significantly associated with recipient-site adverse events in univariate analysis (P < 0.05). Lower body mass index and skeletal muscle index were significantly associated with recipient-site surgical site infection in univariate analysis (P < 0.05). In the multiple logistic regression model, a lower skeletal muscle index was a significant risk factor for recipient-site adverse events and surgical site infections (adverse events odds ratio; 3.17/P = 0.04; surgical site infection odds ratio; 3.76/P = 0.02). CONCLUSIONS: The SMI at level Th12 was an independent factor for postoperative AEs, especially SSI, in OSCC patients with free-flap reconstruction.

Contrast-enhanced computed tomography of retromandibular vein position and course patterns relative to the mandible during sagittal split ramus osteotomy.

Background: Sagittal split ramus osteotomy is an established procedure used in oral and maxillofacial surgery. Major bleeding is representative intraoperative complication involves vessels such as the inferior alveolar, facial, and maxillary arteries and accompanying veins, in particular the retromandibular vein (RMV). We previously described the RMV course patterns using embalmed cadavers. However, owing to the possible influence of formalin fixation and unclear skeletal classification of the jaws, the present study aimed to use contrast-enhanced computed tomography to confirm the RMV in patients with defined jaw deformities. Methods: Twenty patients with orthognathic jaw deformities (40 sides) were included. The RMV and the lateral and posterior views of the mandible were evaluated using contrast-enhanced computed tomography. Course patterns and RMV positions were classified as previously reported. Results: Three patterns were identified in the lateral view. Type A: RMV posterior to the posterior border of the ramus (n=25; 62.5%). Type B: adjoining the posterior border of the ramus (n=12; 30.0%). Type C: anterior to the posterior border of the ramus (n=3; 7.5%). Five course patterns were identified in the posterior view. Pattern I: rectilinear course running medial to the posterior border of the ramus (n=3; 7.5%). Pattern II: diagonal course running medially from immediately posterior to posterior border of the ramus (n=11; 27.5%). Pattern III: rectilinear course running immediately posterior to the posterior border of the ramus (n=12; 30.0%). Pattern IV: diagonal course running from lateral to medial relative to the posterior border of the ramus (n=8; 20.0%). Pattern V: diagonal course running from lateral to immediately posterior relative to the posterior border of the ramus (n=6; 15.0%). In the no-course pattern group, the RMV inferior to the lingula was lateral to its position and superior to that of the lingula. In half of the cases, the left and right sides exhibited different running patterns. We observed no correlation between the skeletal patterns of jaw deformities and the course of the RMV. Conclusions: Type B/Pattern II that runs in a straight line bordering the posterior margin of the ramus requires the most attention during surgery. These findings suggest the possibility of predicting intraoperative bleeding risk.

Dentigerous cysts suspected the other odontogenic lesions on panoramic radiography and CT.

Dentigerous cysts are known as the second most common type of cyst in the jaws. The cyst is one of the lesions occurred frequently in the posterior body of the mandible and is often related to the unerupted third molar and forms around the crown of the unerupted tooth attaching at the cementoenamel junction. Such characteristic appearances are the diagnostic points differentiating from ameloblastoma or odontogenic keratocyst. However, it would be hard for us to diagnose it as a dentigerous cyst if the lesion does not show its typical appearance. We experienced two cases of dentigerous cysts which did not form around the crown of the unerupted tooth on radiologically. Both cysts were relatively large and resorbed adjacent teeth roots. Therefore, an ameloblastoma or an odontogenic keratocyst was suspected rather than a dentigerous cyst as the imaging diagnosis. The biopsy revealed that the lesion was a "dentigerous cyst" in one of the cases and "developmental cyst with inflammation" in another case. After the excision, the histopathological diagnosis was a dentigerous cyst with inflammation in both cases. This report shows the two cases of dentigerous cysts focusing on panoramic radiography and CT images. Also, we discuss the differential diagnosis by reconsidering those diagnostic points.

Enhanced Precision in Genioplasty: A Novel Intraoperative Spatial Repositioning Using Computer-Aided Design and Manufacturing Technology and a Holographic Mixed Reality Application.

Genioplasty is performed for the orthognathic surgical correction of dentofacial deformities. This article reports a safe and accurate method for genioplasty combining a novel three-dimensional (3D) device with mixed reality (MR)-assisted surgery using a registration marker and a head-mounted display. Four types of devices were designed based on the virtual operation: a surgical splint with a connector; an osteotomy device; a repositioning device; and a registration marker. Microsoft HoloLens 2 and Holoeyes MD were used to project holograms created using computed tomography (CT) data onto the surgical field to improve the accuracy of the computer-aided designed and manufactured (CAD/CAM) surgical guides. After making an incision on the oral vestibule, the splint was fitted on the teeth and the osteotomy device was mounted at the junction site, placed directly on the exposed mandible bone surface. Temporary screws were fixed into the screw hole. An ultrasonic cutting instrument was used for the osteotomy. After separating the bone, a repositioning device was connected to the splint junction and bone segment, and repositioning was performed. At the time of repositioning, the registration marker was connected to the splint junction, and mandible repositioning was confirmed three-dimensionally through HoloLens 2 into the position specified in the virtual surgery. The rate of overlay error between the preoperative virtual operation and one-month postoperative CT data within 2 mm was 100%. CAD/CAM combined with MR enabled accurate genioplasty.

Increased RUNX3 expression mediates tumor-promoting ability of human breast cancer-associated fibroblasts.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a major stromal component of human breast cancers and often promote tumor proliferation, progression and malignancy. We previously established an experimental CAF (exp-CAF) cell line equipped with a potent tumor-promoting ability. It was generated through prolonged incubation of immortalized human mammary fibroblasts with human breast cancer cells in a tumor xenograft mouse model. RESULTS: Herein, we found that the exp-CAFs highly express Runt-related transcription factor 3 (RUNX3), while counterpart fibroblasts do not. In breast cancer patients, the proportion of RUNX3-positive stromal fibroblast-like cells tends to be higher in cancerous regions than in non-cancerous regions. These findings suggest an association of RUNX3 with CAF characteristics in human breast cancers. To investigate the functional role of RUNX3 in CAFs, the exp-CAFs with or without shRNA-directed knockdown of RUNX3 were implanted with breast cancer cells subcutaneously in immunodeficient mice. Comparison of the resulting xenograft tumors revealed that tumor growth was significantly attenuated when RUNX3 expression was suppressed in the fibroblasts. Consistently, Ki-67 and CD31 immunohistochemical staining of the tumor sections indicated reduction of cancer cell proliferation and microvessel formation in the tumors formed with the RUNX3-suppressed exp-CAFs. CONCLUSION: These results suggest that increased RUNX3 expression could contribute to the tumor-promoting ability of CAFs through mediating cancer cell growth and neoangiogenesis in human breast tumors.

Kissing molars class III detected at a young age.

BACKGROUND: Kissing molars (KMs) is defined as a state in which the apex of two impacted molars face opposite directions and the occlusal surfaces touch each other and the crown is in one follicle. Class III KMs have been reported previously; however, reports on class III KMs in young people (< 18 years of age) are limited. CASE PRESENTATION: Here, we present the case of KMs class III confirmed at an early age, supported by a review of the literature. The patient was a 16-year-old female and experienced discomfort in the left molar of the lower jaw and visited in our department. We diagnosed KMs based on an impacted teeth on the buccal side, near the lower jaw wisdom teeth, and a cyst-like low-density area observed around the crown of both teeth, as revealed by computed tomography. We decide to extract the tooth and enucleate the cyst under local anesthesia as the patient experienced discomfort due to occlusion. Furthermore, the cyst-like structure removal and tooth extraction including tooth root were necessary as the patient had KM class III, possibly inducing complicated malocclusion. Although no previous reports recommended timing for KMs tooth extraction, we propose that extraction at an early stage is important regardless of age especially in class III cases. CONCLUSIONS: We report a case of KM class III detected at an early age.

Ameloblastic carcinoma of the mandible: a case report.

BACKGROUND: Ameloblastic carcinoma is a malignant form of ameloblastoma and a very rare odontogenic tumor. We report a case of ameloblastic carcinoma that occurred after removal of a right-sided mandibular dental implant. CASE PRESENTATION: A 72-year-old female patient visited her family dentist with a complaint of pain around a lower right implant placed 37 years previously. Although the dental implant was removed with the diagnosis of peri-implantitis, the patient experienced dullness of sensation in the lower lip and was followed up by her dentist, but after no improvement. She was referred to a highly specialized institution where she was diagnosed with osteomyelitis and treated the patient with medication; however, there was no improvement. In addition, granulation was observed in the same area leading to a suspicion of malignancy, and the patient was referred to our oral cancer center. The diagnosis of squamous cell carcinoma was made after a biopsy at our hospital. Under general anesthesia, the patient underwent mandibulectomy, right-sided neck dissection, free flap reconstruction with an anterolateral thigh flap, immediate reconstruction with a metal plate, and tracheostomy. Histological analysis of the resected specimen on hematoxylin and eosin staining showed structures reminiscent of enamel pulp and squamous epithelium in the center of the tumor. The tumor cells were highly atypical, with nuclear staining, hypertrophy, irregular nuclear size, and irregular nuclear shape, all of which were suggestive of cancer. Immunohistochemical analysis showed that Ki-67 was expressed in more than 80% of the targeted area, and the final diagnosis was primary ameloblastic carcinoma. CONCLUSION: After reconstructive flap transplantation, occlusion was re-established using a maxillofacial prosthesis. The patient remained disease-free at the 1-year 3-month follow-up.

Intraoral Minor Salivary Gland Tumors: A Retrospective, Clinicopathologic, Single-Center Study of 432 Cases in Japan and a Comparison with Epidemiological Data.

BACKGROUND: Intraoral minor salivary gland tumors are relatively rare lesions with histological subtypes not commonly found in major salivary glands. This study aimed to retrospectively evaluate the clinicopathologic features of intraoral minor salivary gland tumors from the Tokyo Dental College Hospital, Japan, and compare them with findings from other epidemiological studies. METHODS: We conducted a retrospective clinicopathologic evaluation of 432 cases of intraoral minor salivary gland tumors [161 male (37.3%) and 271 female (62.7%) patients; mean age: 52.5 and 48.6 years for males and females, respectively; age at diagnosis: 7-87 (mean: 50.1) years] from the Tokyo Dental College Hospital between 1975 and 2022, including 283 benign tumors (65.5%) and 149 malignant tumors (34.5%). RESULTS: The most common benign tumor was pleomorphic adenoma (n = 239), whereas mucoepidermoid carcinoma was the most common malignant tumor (n = 74). The mean age of patients with benign and malignant tumors was 48.4 and 53.2 years, respectively, with patients with malignant tumors being significantly older (P = 0.0042). The mean age of patients with malignant tumors was significantly higher in males (56.7 years) than in females (50.9 years) (P = 0.0376), although the mean age of patients with benign tumors did not differ by sex. Tumors were commonly located in the palate [250 cases (57.9%)]. Benign tumors were more frequent in the palate, upper lip, and buccal mucosa, whereas malignant tumors were more frequent in the palate, floor of the mouth, buccal mucosa, and retromolar area. CONCLUSIONS: Understanding the features of intraoral minor salivary gland tumors is useful for diagnosis. Our study provides important epidemiological data (patient differences in age at occurrence, sex, and site of origin) that will inform clinicians and researchers.

Subset of the periodontal ligament expressed leptin receptor contributes to part of hard tissue-forming cells.

The lineage of periodontal ligament (PDL) stem cells contributes to alveolar bone (AB) and cementum formation, which are essential for tooth-jawbone attachment. Leptin receptor (LepR), a skeletal stem cell marker, is expressed in PDL; however, the stem cell capacity of LepR+ PDL cells remains unclear. We used a Cre/LoxP-based approach and detected LepR-cre-labeled cells in the perivascular around the root apex; their number increased with age. In the juvenile stage, LepR+ PDL cells differentiated into AB-embedded osteocytes rather than cementocytes, but their contribution to both increased with age. The frequency of LepR+ PDL cell-derived lineages in hard tissue was < 20% per total cells at 1-year-old. Similarly, LepR+ PDL cells differentiated into osteocytes following tooth extraction, but their frequency was < 9%. Additionally, both LepR+ and LepR- PDL cells demonstrated spheroid-forming capacity, which is an indicator of self-renewal. These results indicate that both LepR+ and LepR- PDL populations contributed to hard tissue formation. LepR- PDL cells increased the expression of LepR during spheroid formation, suggesting that the LepR- PDL cells may hierarchically sit upstream of LepR+ PDL cells. Collectively, the origin of hard tissue-forming cells in the PDL is heterogeneous, some of which express LepR.

Functional Expression of Mechanosensitive Piezo1/TRPV4 Channels in Mouse Osteoblasts.

Mechanical stress is an important regulatory factor in bone homeostasis. Mechanical stimulation of osteoblasts has been shown to elicit an increase in the concentration of intracellular free Ca2+ ([Ca2+]i). The pattern of functional expression of mechanosensitive ion channels remains unclear, however. Therefore, the purpose of this study was to investigate the pharmacological characteristics of [Ca2+]i in response to direct mechanical stimulation in osteoblasts. The morphological expression of mechanosensitive ion channels was also examined. Mouse osteoblast-like cells (MC3T3-E1 cells) were loaded with fura-2-acetoxymethyl ester, after which [Ca2+]i was measured. Increased levels of [Ca2+]i were observed in MC3T3-E1 cells in response to direct mechanical stimulation by means of a glass micropipette, but no desensitization. Application of a hypotonic solution also induced an increase in [Ca2+]i but was accompanied by a desensitizing effect. Extracellular Gd3+, GsMTx4, or RN-1734 reversibly inhibited this mechanical stimulation-induced increase in [Ca2+]i, whereas no inhibitory effect was observed with HC030031 or clemizole. When osteoblasts were stimulated with Yoda1, an increase was observed in [Ca2+]i together with a significant desensitizing effect. Immunoreactivity against Piezo1 and TRPV4 channel antibodies was detected in MC3T3-E1 cells. These results suggest that osteoblasts express Piezo1 and TRPV4 channels, which are involved in mechanosensitive processes during mechanical stress.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue. A biopsy resulted in a diagnosis of a well-differentiated squamous cell carcinoma of the tongue, for which a partial resection was subsequently performed. During regular follow-up, the patient demonstrated no clinical or imaging abnormalities until 4 years and 9 months later, when erosion was observed at the right palatoglossal arch. A malignant tumor of the right palatoglossal arch was diagnosed based on cytology and imaging findings, and total resection of the lesion performed. Histopathological examination of the resected lesion revealed a moderately differentiated squamous cell carcinoma. Epithelial dysplasia on the right-hand margin of the tongue was diagnosed 4 years and 9 months after the second surgery and was subsequently resected. The patient's condition has been favorable for 7 years since the diagnosis of the second cancer, with no noted recurrence. This case emphasizes the importance of follow-up after initial treatment, as even young people, who are likely to have to endure long-lasting consequences from treatment, can develop metachronous cancer in the oral cavity.

Mixed reality for extraction of maxillary mesiodens.

BACKGROUND: Mesiodentes are the most common supernumerary teeth. The cause is not fully understood, although proliferations of genetic factors and the dental lamina have been implicated. Mesiodentes can cause delayed or ectopic eruption of permanent incisors, which can further alter occlusion and appearance. Careful attention should be paid to the position and direction of the mesiodentes because of possible damage to adjacent roots in the permanent dentition period, errant extraction in the deciduous and mixed dentition periods, and damage to the permanent tooth embryo. To avoid these complications, we applied mixed reality (MR) technology using the HoloLens® (Microsoft, California). In this study, we report on three cases of mesiodentes extraction under general anesthesia using MR technology. RESULTS: The patients ranged in age from 6 to 11 years, all three were boys, and the direction of eruption was inverted in all cases. The extraction approach was palatal in two cases and labial in one case. The average operative time was 32 min, and bleeding was minimal in all cases. No intraoperative or postoperative complications occurred. An image was shared preoperatively with all the surgeons using an actual situation model. Three surgeons used Microsoft HoloLens® during surgery, shared MR, and operated while superimposing the application image in the surgical field. CONCLUSIONS: The procedure was performed safely; further development of MR surgery support systems in the future is suggested.

Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.