p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs).

To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus (p < 0.01) and positively correlated with p62 expression in the cytoplasm (p < 0.01). For malignant transformation, the expression of p62 in the nucleus (p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm (p = 0.03) and the aggregation expression (p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.

Anterior Maxillary Distraction Osteogenesis With Bone-borne Intraoral Buccal Devices for Maxillary Hypoplasia With Cleft Lip and Palate.

Anterior maxillary distraction osteogenesis (AMDO) surgery for cleft lip and palate involves distraction of a segment of the anterior maxilla and advancement using 2 intraoral buccal bone-borne distraction devices. The anterior part of the maxilla is advanced anteriorly with less relapse which increases maxillary length and does not affect speech. We aimed to evaluate the effects of AMDO, including lateral cephalometric changes. Seventeen patients who had undergone this procedure were included in this retrospective study. The distractors were activated by 0.5 mm twice a day after a 3-day latency period. Lateral cephalometric radiographs were evaluated preoperatively, after distraction and removal of distractors, which were compared using the paired Student's t test. Anterior maxillary advancement was obtained in all patients with a median of 8.0 mm. Complications included nasal bleeding and loosening of distractors; however, there was no tooth damage or abnormal movement. The mean sella-nasion-A point (SNA) angle increased significantly, from 74.91° to 79.66°, the A point-nasion-B point angle from -0.38° to 4.34°, and the perpendicular line from nasion to Frankfort Horizontal (NV)-A point from -5.11 to 0.08 mm. The mean anterior nasal spine-posterior nasal spine length increased significantly from 50.74 to 55.10 mm, and the NV-Nose Tip from 23.59 to 26.27 mm. The mean relapse rate of NV-A was 11.1%. AMDO with bone-borne distractor resulted in less relapse and effectively corrected the maxillary retrusion.

Is Preoperative Plate-Lymphocyte Ratio a Predictor of Deep Vein Thrombosis in Patients With Oral Cancer During Surgery?

PURPOSE: Detecting deep vein thrombosis (DVT) is necessary to reduce the morbidity of venous thromboembolism, and platelet-lymphocyte ratio (PLR) is a novel marker for predicting DVT. This study aimed to investigate the association between preoperative PLR and risk of developing DVT in patients receiving surgical treatment of oral cancer. PATIENTS AND METHODS: We designed a retrospective cohort study, and the source of study sample was patients with oral cancer and who underwent surgery between 2015 and 2019. Patients were excluded if they did not undergo surgical treatment and had preoperative DVT and history of hypercoagulable disorders. The primary predictor variable was PLR. We calculated the receiver operating characteristic curve and area under the curve to determine the best-defined risk groups. The best cutoff value for PLR was 187.4 (area under the curve, 0.772; sensitivity, 75.0%; specificity, 74.2%; P = .002). The primary outcome variable was DVT, and the other variables were patient characteristics, blood examination data, and therapeutic data. A logistic regression analysis was used to adjust the effects of potential confounders. RESULTS: A total of 101 patients were included in this study, and DVT was observed in 12 (11.9%) patients. Free flap reconstructive surgery was performed in 8 of the 12 (66.7%) patients in the DVT group. Statistical analyses showed that DVT was significantly associated with PLR (≤187.4 vs >187.4; P = .001). Logistic multivariate analysis of the preoperative parameters identified the following 2 independent predictive factors for DVT: PLR (≤187.4 vs >187.4) (odds ratio, 13.735; 95% confidence interval, 2.950 to 63.944; P = .001) and free flap reconstructive surgery (odds ratio, 6.584; 95% confidence interval, 1.504 to 28.822; P = .012). CONCLUSIONS: High PLR (>187.4) and free flap reconstructive surgery, considered as preoperative predictive factors, were associated with DVT.

Is Lymph Node Ratio a Prognostic Factor for Patients With Oral Squamous Cell Carcinoma?

PURPOSE: Lymph node ratio (LNR), defined as the ratio of positive resected lymph nodes (LNs) to the total number of resected LNs, predicts survival for some solid tumors. This study investigated the value of LNR in the prognosis and postsurgical management of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The authors designed a retrospective cohort study and enrolled a sample of patients who were diagnosed with OSCC and treated by neck dissection. The predictor was LNR and the outcome variable was overall survival (OS). Other variables were dissection type, postsurgical management, number of positive LNs, pN stage, nodal disease area, extracapsular spread, perineural invasion, vascular invasion, and lymph duct invasion. Differences in OS rate were analyzed by log-rank test. A Cox proportional hazards model was used to adjust for the effects of potential confounders. Differences with a P value less than .05 were considered statistically significant. RESULTS: In 95 patients with OSCC, the LNR cutoff value for predicting overall OS was 0.04 (area under the curve, 0.705; P = .010). There was a significant difference in OS when patients were stratified according to LNR (rate for low LNR, 90.5%; rate for high LNR, 68.8%; P = .014). Univariate analyses showed close correlations between OS and LNR, pT stage, number of positive LNs, and nodal disease area (levels IV and V). Cox multivariate analysis identified LNR (hazard ratio [HR] = 2.889; 95% confidence interval [CI], 1.032-8.087; P = .043) and area of nodal disease (levels IV and V; HR = 5.149; 95% CI, 1.428-18.566; P = .012) as independent predictive factors for OS. OS differed significantly between the high-LNR and low-LNR groups treated by surgery alone (P = .027). CONCLUSIONS: As a predictive factor, high LNR (>0.04) was associated with decreased survival, and intensive adjuvant therapy could improve the prognosis for patients with high LNR.

MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis.

BACKGROUND: Abnormal miRNA expression was recently implicated in the metastasis of oral squamous cell carcinoma (OSCC) and with a poor prognosis. The initiation of the invasion-metastasis cascade involves epithelial-mesenchymal transition (EMT). Our aim was to clarify how miRNA, especially miR-155-5p misexpression contributes to OSCC metastasis through EMT. METHODS: We collected tumor samples from 73 subjects with OSCC. The samples were analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and correlations between miR-155-5p levels and clinical characteristics were investigated. OSCC cell lines were analyzed by miRNA microarray and by transfection with a miR-155-5p mimic or inhibitor, followed by proliferation and wound-healing migration assays. qRT-PCR analyses of EMT makers in cells transfected with miR-155-5p inhibitor were performed. RESULTS: We found high miR-155-5p expression in tissue samples from subjects with OSCC that had metastasized to cervical lymph nodes. HSC-3 cells also strongly expressed miR-155-5p. The epithelial marker E-cadherin was strongly expressed in HSC-3 cells transfected with miR-155-5p inhibitor, and we observed elevated SOCS1 and decreased STAT3 expression in these cells. CONCLUSIONS: Our results suggest that miR-155-5p causes OSCC to metastasize, and could serve as a novel therapeutic target for OSCC.

Involvement of submandibular gland in oral squamous cell carcinoma.

BACKGROUND: The submandibular gland (SMG) is sacrificed during neck dissection in patients undergoing curative surgery for oral squamous cell carcinoma (OSCC). This may cause a decrease in the production of saliva and result in xerostomia. PURPOSE: This study aimed to determine the incidence, invasion patterns, risk factors, and prognosis of SMG involvement in OSCC. METHODS: The primary predictor variable in this study was SMG involvement, and the secondary predictor was prognosis. MAIN FINDINGS: The primary outcome variables were patient characteristics and pathological results for extranodal extension (ENE), perineural invasion (PNI), and pN stage. Four out of 173 patients (2.23 %) showed SMG involvement. Of these cases, one (25 %) was from the primary lesion and three (75 %) were from the metastatic neck lymph nodes (LNs). The primary lesion was located on the lower gingiva, and the other three were from level-Ib LNs with ENE. The pathological PNI was observed in three of the four patients, and ENE was observed in three of the four patients. Preoperative CT and MR revealed SMG invasion and contact in two patients. There were significant differences in the ENE and pN stages between patients with and without SMG involvement (P<0.05). There was a significant difference in the overall survival between patients with (25.0 %) and without (71.5 %) SMG involvement (P = 0.011). CONCLUSIONS: SMG involvement was associated with ENE, pN stage, and poor prognosis.

Predictors of Occult Metastasis and Prognostic Factors in Patients with cN0 Oral Cancer Who Underwent Elective Neck Dissection.

Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary.

Analysis of predictors of fever after aortic valve replacement: Diabetic patients are less likely to develop fever after aortic valve replacement, a single-centre retrospective study.

BACKGROUND: Postoperative temperature dysregulation affects the length of hospital stay and prognosis. This study evaluated the factors that influence the occurrence of fever in patients after aortic valve replacement surgery. METHODS: Eighty-seven consecutive patients who underwent aortic valve replacement surgery were included. Patients' age, sex and body mass index; presence of diabetes mellitus; operation time; blood loss; blood transfusion volume; preoperative and postoperative laboratory findings; presence or absence of oral function management; and fever >38°C were retrospectively analysed through univariate and multiple logistic regression analyses. RESULTS: Among the variables, only diabetes mellitus status was significantly associated with fever ⩾38°C. Postoperatively, patients with diabetes mellitus were significantly less likely to develop fever above 38°C and a fever rising to 38°C. CONCLUSIONS: This study shows that the presence of comorbid diabetes mellitus decreases the frequency of developing fever >38°C after aortic valve replacement surgery.

A Case of Primary Intraosseous Squamous Cell Carcinoma Arising in Dentigerous Cyst of Mandible.

Primary intraosseous squamous cell carcinoma (PISCC) arising from dentigerous cysts (DCs) is rare. Herein, we present a rare case of a 35 year-old Japanese man with PISCC arising from a DC. Clinicians should be aware of the potential for malignant changes to SCC in asymptomatic DCs and should conduct follow-up. Moreover, histological examination of the entire specimen should be performed even if the lesion is suspected to be benign.

Postoperative Deep Sedation after Microvascular Reconstructive Surgery for Oral Cancer Increases the Risk of Early Postoperative Pneumonia.

This study investigated the effect of postoperative deep sedation after oral cancer reconstructive surgery on the occurrence of early postoperative pneumonia and early postoperative delirium. We obtained medical records of 108 consecutive patients who underwent microvascular reconstructive surgery at Tsukuba University Hospital for oral cancer between January 2013 and December 2021. Forty-six of them woke soon after surgery. Ten of these forty-six patients were restless and required immediate sedation within 3 h after surgery. The comparison between sedation group and no sedation group revealed early postoperative pneumonia in the no sedation group; however, sedation was not related to early postoperative delirium. The preoperative albumin levels of patients with postoperative pneumonia were significantly different (p = 0.03) than those of patients without postoperative pneumonia. The performance status (p = 0.02), preoperative albumin level (p = 0.02), and age 75 years or older (p = 0.02) were significantly associated with postoperative delirium. Restless patients and those who could not be sedated experienced delirium and pneumonia. The risk of pneumonia was increased for patients who were difficult to sedate.

A Case of Tophaceous Pseudogout with Destruction of the Skull Base at the Temporomandibular Joint.

We report a case of tophaceous pseudogout that occurred in the temporomandibular joint (TMJ) and presented with skull base destruction. The patient was a 73-year-old woman, who complained of an obstructed ear sensation in December 2021. The otolaryngological examination was unremarkeable, and a computed tomography scan revealed a calcified lesion in the left TMJ. Suspected of having osteochondroma, the patient was brought to our hospital. She was performed tumor resection as much as possible under general anesthesia revealed nodular pseudogout. The patient refused to undergo total resection due to the necessary craniotomy and the risk of postoperative complications. Instead, the patient decided to undergo following-up. One year and 4 months have passed since the biopsy operation, but there is no tendency to re-increase.

Proton beam therapy for cervical lymph node metastasis in an octogenarian with melanoma of unknown primary: a case report.

An 80-year-old man with an approximately 3-cm mass in the right submandibular region presented to our institution. Magnetic resonance imaging revealed enlarged lymph nodes (LNs) in the right neck, and fluorine-18-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) indicated positive FDG accumulation in the right neck LNs only. Excisional biopsy was performed for suspected malignant lymphoma, and the biopsy revealed melanoma. Close examination of the skin, nasal cavity, oral pharyngeal and laryngeal cavities, and gastrointestinal tract were performed. No primary tumor was detected by these examinations, and the patient was diagnosed with cervical LN metastasis from melanoma of unknown primary of clinical stage T0N3bM0 stage IIIC. The patient refused cervical neck dissection because of his age and comorbidity of Alzheimer's disease and instead opted for proton beam therapy (PBT) at a total dose of 69 Gy (relative biological effectiveness) in 23 fractions. He did not receive any systemic therapy. The enlarged LNs shrunk slowly, and FDG PET/CT at 1 year after PBT showed that the right submandibular LN had shrunk from 27 to 7 mm in length, and there was no significant FDG accumulation. At 6 years and 4 months after PBT, the patient is alive without any recurrence.

A Case of Tooth Extraction in a Patient with Food-Dependent Exercise Induced Anaphylaxis.

A 29-year-old Japanese man with food-dependent exercise-induced anaphylaxis (FDEIA) underwent tooth extraction under general anesthesia. FDEIA is a rare condition in which anaphylaxis occurs due to exercise load or oral administration of NSAIDs after ingestion of allergens. Wheat is often the cause in FEDIA, defined as wheat-dependent exercise-induced anaphylaxis (WDEIA). It is an allergy that is not well known in the dental field. Patients may ingest the causative food on a regular basis because they do not develop without factors such as exercise. Post extraction period was uneventful as the patient was instructed not to ingest wheat before the treatment or while he was taking NSAIDs. We were able to safely extract teeth without causing anaphylaxis.

Prognostic prediction using maximum standardized uptake value ratio of lymph node-to-primary tumor in preoperative PET-CT for oral squamous cell carcinoma.

This study aimed to calculate the ratio of maximum standardized uptake values of cervical lymph nodes to maximum standardized uptake values of primary tumors measured by preoperative fluorodeoxyglucose positron-emission tomography in oral cancer patients, and to retrospectively examine the prognostic association and evaluate whether it could be a prognostic factor. We retrospectively examined consecutive Japanese patients diagnosed with oral squamous cell carcinoma who underwent oral cancer resection and cervical dissection between January 2014 and December 2018. The study included 52 patients aged 39-89 years (median age 66.5 years), excluding non-cervical dissection surgery and/or non-underwent preoperative positron-emission tomography. The maximum standardized uptake value of the cervical lymph nodes and primary tumor was measured, and the ratio of maximum standardized uptake values of the lymph nodes to that of the primary tumor was calculated. The median follow-up of 52 patients was 1,465 days (198-2,553 days), and overall survival was significantly worse in patients with a high lymph node-to-tumor standardized uptake values ratio (>0.4739) (5 years, 58.8% vs. 88.2%; P<0.05). Pretreatment lymph node-to-tumor standardized uptake values ratio can be easily calculated, and as a predictor of prognosis, it may be of assistance when considering the treatment strategy for oral cancer.

A Case of Primary Intraosseous Adenoid Cystic Carcinoma of the Mandible.

Primary intraosseous adenoid cystic carcinoma (PIACC) of the jaw is rare. To our knowledge, only 51 cases have been reported in the English literature. We present a rare case of PIACC arising in the mandible with multiple bone metastases and review the previous articles. A 70-year-old woman presented with paresthesia of the right chin and lower gingiva for 4 months. Radiography revealed an irregular radiolucent region on the right side of the ramus, infiltrating to the mandibular canal. Biopsy revealed a pathological diagnosis of adenoid cystic carcinoma. Multiple bone metastases were present in the sternum, scapula, and thighs. The treatment effect was progressive disease for chemotherapy; therefore, best supportive care was provided for 3 years.

Macrophage specific restoration of the Nrf2 gene in whole-body knockout mice ameliorates steatohepatitis induced by lipopolysaccharide from Porphyromonas gingivalis through enhanced hepatic clearance.

Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (P.g.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P.g. We generated macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-mRes mice were fed a high-fat diet for 18 weeks, and LPS from P.g. was administered intraperitoneally for the last 6 weeks. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The mRNA expressions of Toll-like receptor (Tlr)-2, which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin (αSma), which promotes hepatic fibrosis, were reduced in Nrf2-mRes mice compared with Nrf2-KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2-KO mice compared with WT mice; however, the levels were reduced in Nrf2-mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS.

Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest.

BACKGROUND: Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. METHODS: We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. RESULTS: The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21(Cip1), p27(Kip1), p15(INK4B), and p16(INK4A)) in the knockdown cells. CONCLUSION: The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors.

Anatomical Variant of Spinal Accessory Nerve Passing through Fenestrated Internal Jugular Vein.

Neck dissection (ND) is a major surgery for head and neck cancer. Currently, some or all of the spinal accessory nerve (SAN), sternocleidomastoid muscle, and internal jugular vein (IJV) are aggressively preserved during ND to reduce postoperative complications. Since the anatomical relationship between the SAN and IJV has several variations, knowledge of these variations is necessary to avoid iatrogenic damage. In the present case, the SAN was observed to pass through the fenestrated IJV at the level of the posterior belly of the digastric muscle during ND in a patient with squamous cell carcinoma of the mandible. Although the anatomical structure of the SAN and IJV is rare, surgeons must be aware of this anatomical variation.

Dedifferentiated Low-Grade Central Osteosarcoma of the Mandible.

We present the first, to our knowledge, case of a dedifferentiated low-grade central osteosarcoma (LCOS) of the mandible. A 48-year-old Japanese woman underwent enucleation under general anesthesia after a diagnosis of ossifying fibroma. At the second recurrence, the pathological diagnosis after biopsy was of sarcoma with MDM2(+) and CDK4(+) immunohistochemical staining results. Hemimandibulotomy, supraomohyoid neck dissection, and free-flap reconstruction with a rectus abdominal flap were performed. A retrospective reevaluation of the first specimen with additional immunohistochemical staining for MDM2 and CDK4 yielded a final diagnosis of dedifferentiated LCOS. The patient showed no recurrence or lung metastasis 3 years after the final surgery.

Accidental Insertion of a Broken Needle into the Pterygoid Mandibular Space during Inferior Alveolar Nerve Block: A Case Report.

The incidence of needle breakage is estimated to be 0.000007%, and most needle breaks occur during inferior alveolar nerve block (IANB) administration and are localized to the pterygomandibular space. Although immediate surgical intervention is recommended for the removal of the fracture needles, intraoperative localization of a broken injection needle fragment can be challenging. Here, we present the case of a 36-year-old woman who underwent dental extraction of the left lower wisdom tooth under local anesthesia at a private office. At that time, a disposable 33G needle was broken and accidentally inserted into the pterygomandibular space during IANB. A broken injection needle was presented at the base of the left coronoid process of the mandible on computed tomography (CT). We successfully removed the broken injection needle using fluoroscopy and assisted endoscopy under general anesthesia.