Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with recurrent oral squamous cell carcinoma treated with nivolumab.

The immune checkpoint inhibitor (ICI), nivolumab, has revolutionised the treatment of recurrent and metastatic oral cancer. However, the response rate to ICIs remains low, and identifying predictors of nivolumab response is critical. Although the neutrophil-to-lymphocyte ratio (NLR) has been suggested as a predictive marker of nivolumab response in patients with various types of cancer, its utility in oral squamous cell carcinoma (OSCC) has not been elucidated. In this retrospective multicentre cohort study, we evaluated the association between NLR and outcome of nivolumab treatment in 64 patients with OSCC treated between 2017 and 2020. The objective response and disease control rates were 25.1% and 32.9%, respectively. The rates for complete and partial responses were 15.7% (10/64) and 9.4% (6/64), respectively; stable and progressive disease rates were 7.8% (5/64) and 67.1% (43/64), respectively. Complete and partial responses were classified as responders, and stable and progressive diseases were classified as non-responders. The median (range) pre-treatment NLR among responders was 4.3 (2.8-8.0), which decreased to 4.0 (2.6-6.3) after nivolumab treatment, and the median (range) pre-treatment NLR among non-responders was 5.1 (2.7-7.9), which increased to 6.4 (4.0-14.0) with tumour growth. Moreover, overall survival was significantly worse in the group with a higher post-treatment NLR (≥5) than in the group with a lower NLR (<5). Patients with a post-treatment NLR of ≥6 had worse outcomes for salvage chemotherapy following nivolumab treatment. Thus, post-treatment NLR could be a useful marker for predicting the response to nivolumab treatment or salvage chemotherapy in patients with OSCC.

Predictive Value of Neutrophil-Lymphocyte Ratio as a Marker in Antiresorptive Agent-Related Osteonecrosis of the Jaw: A Retrospective Analysis.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ), a multifactorial disease, can drastically affect a patient's quality of life. Moreover, disease progression to severe acute inflammation can hinder treatment. Therefore, we aimed to investigate the diagnostic value of the neutrophil−lymphocyte ratio (NLR) and platelet−lymphocyte ratio (PLR) in predicting the risk of acute inflammation in patients with ARONJ. In total, 147 patients with ARONJ were enrolled between 1 January 2011 and 31 December 2019. They were divided into two groups according to their baseline NLR (high NLR vs. low NLR) or PLR (high PLR vs. low PLR) to analyze the relationship between NLR and PLR and the outcomes of acute inflammatory events. An optimal NLR cut-off value of 2.83 was identified for hospitalization for an inflammatory event. Logistic regression analysis showed that NLR > 2.83 was associated with an increased risk of hospitalization for an inflammatory event. A PLR cut-off value of 165.2 was identified for hospitalization for an inflammatory event. However, logistic regression analysis showed that PLR > 165.2 was not significantly associated with hospitalization for an inflammatory event. Our study findings suggest that the NLR has diagnostic value in predicting the risk of hospitalization for inflammatory events among patients with ARONJ.

Intra-arterial chemoradiotherapy for locally advanced buccal mucosal cancer in an elderly patient with multiple comorbidities: A case report.

BACKGROUND: The management of locally advanced oral cavity squamous cell carcinoma (LA-OCScc) in elderly patients with multiple comorbidities is difficult. CASE: We report the case of an elderly patient with buccal mucosal squamous cell carcinoma as well as chronic renal dysfunction, hepatic cirrhosis, rheumatoid arthritis, and metachronous diffuse large B-cell lymphoma. We performed radiation therapy (a total dose of 70 Gy in 35 fractions) and six cycles of intra-arterial chemotherapy with 40 mg/m2 cisplatin per week. After treatment, the tumor completely disappeared, and there was no recurrence or deterioration of comorbidities during the 12-month follow-up period. CONCLUSION: Intra-arterial chemoradiotherapy may be a good treatment option for LA-OCScc in elderly patients with multiple comorbidities.

Oral Management of a Haematopoietic Stem Cell Transplant Recipient with Chédiak-Higashi Syndrome.

Chédiak-Higashi syndrome (CHS), a rare autosomal recessive disorder associated with leukocyte dysfunction, is characterised by partial skin and hair albinism, immunodeficiency, and abnormal bleeding. Furthermore, it may be associated with cognitive and neurological impairments. The long-term prognosis of patients is generally poor, and haematopoietic stem cell transplantation is a radical immunodeficiency treatment. Here, we report a case of successful oral management of an 18-year-old woman with CHS accompanied by aggressive periodontitis who underwent haematopoietic stem cell transplantation.

Role of Phosphodiesterase2A in Proliferation and Migration of Human Osteosarcoma Cells.

BACKGROUND/AIM: The prognosis of patients with osteosarcoma is poor; therefore, new treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of the 11 families (PDE1-PDE11) of the phosphodiesterase superfamily that regulates the intracellular concentrations and effects of cAMP and cGMP. This in vitro study was performed to investigate the role of PDE2 in human oral osteosarcoma HOSM-1 cells. MATERIALS AND METHODS: PDE2 expression was measured by a cAMP-PDE assay and real-time-PCR. The effects of the PDE2-specific inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 8-bromo-cAMP, and 8-bromo-cGMP on cell proliferation and migration were assessed. RESULTS: PDE2 activity and PDE2A mRNA expression were detected in HOSM-1 cells. Cell proliferation was inhibited by EHNA and 8-bromo-cAMP but not by 8-bromo-cGMP. Cell migration was stimulated by EHNA and 8-bromo-cGMP, but it was inhibited by 8-bromo-cAMP. CONCLUSION: Cell proliferation is regulated by PDE2-cAMP signaling and cell migration is regulated by PDE2-cGMP signaling in HOSM-1 cells.

Skeletal stability after maxillary step osteotomy compared with original Le Fort I osteotomy during one-year of follow-up.

The purpose of the current study was to compare the 1-year stability of skeletal after original Le Fort I osteotomy and maxillary step osteotomy. Fifty-two patients with prognathism underwent sagittal split ramus osteotomy with either original Le Fort I osteotomy or maxillary step osteotomy (26 patients each). Twelve cephalometric parameters were measured to evaluate postsurgical stability (lesser change was considered as enhanced stability) at 1 month (T1), 6 months (T2), and 1 year (T3) postoperatively. Only 3 parameters-vertical and horizontal distance of menton and vertical distance of point B-showed minimal but significant differences between the two groups. Lesser degrees of changes were observed after maxillary step osteotomy than after original Le Fort I osteotomy, and the differences were significant during the period between T1 and T2, but not from T1 to T3. Differences between the two groups were less in asymmetry cases required correction of the occlusal plane. In conclusion, differences between original Le Fort I osteotomy and maxillary step osteotomy were observed at the frontal points of the mandible; however, they were not clinically significant. It may be suggested that there is no significant difference in skeletal stability at 1 year after the two procedures.

Evaluation of a New Hydroxyapatite Nanoparticle as a Drug Delivery System to Oral Squamous Cell Carcinoma Cells.

BACKGROUND/AIM: Due to its abilities of substance adsorption and intracellular transportation, hydroxyapatite is a potential carrier in drug delivery systems (DDS). This in vitro study investigated whether newly-developed, highly-dispersive calcined hydroxyapatite nanoparticles with an average grain diameter of 20 nm (nano-SHAP) were suitable as a DDS for the drugs zoledronic acid (ZA), cisplatin, and carboplatin. MATERIAL AND METHODS: The effects of drug-bearing nano-SHAP on cell proliferation were assessed using three human oral squamous cell carcinoma cell lines (HSC-4, KOSC, and SAS) and one human breast cancer cell line (MCF-7). RESULTS: Nano-SHAP alone did not affect proliferation of any cell line until a concentration of 1 µg/ml was reached. Although the effective concentration of ZA in ZA-bearing nano-SHAP differed, it inhibited cell proliferation better than ZA alone. Cisplatin and carboplatin-bearing nano-SHAP had the same effect as these drugs alone. CONCLUSION: The nano-SHAP system is of potential use as a drug delivery system.

The glomus tumor resorbed bone and teeth in the mandible: a case report.

BACKGROUND: A glomus tumor is a rare neoplasm usually found in the dermis or subcutaneous tissue of the extremities. It is rare for the glomus tumor to occur on the head and face. Only 26 glomus tumors of the oral region and affected bone have been reported in the English-language literature (Table 1). We report a case of a glomus tumor at the mandible. As a new point, the glomus tumor resorbed a bone and teeth roots when the tumor progressed into the mandible. CASE PRESENTATION: The patient was a 44-year-old Japanese man who complained swelling of the right mandible. Radiographic examination showed a multilocular radiolucency area in the left mandible. Radiographic findings on our case resembled those of a common benign tumor. The lesion occupied to the premolar and molar area and revealed that the tumor resorbed the roots of the teeth. The lesion was removed surgically with the buccal cortical bone and buccal mucosa in contact with the mass of the tumor. The mass fully excised intraorally under general anesthesia, and the inferior alveolar nerve in contact with the mass was preserved. The specimen was pathologically diagnosed as a glomus tumor. Immunohistochemical staining was positive for vimentin, muscle-specific actin/HHF35, and calponin. A hairline-shaped area of positive staining for type IV collagen surrounding the tumor cells was also observed. In contrast, staining for alpha-SMA, cytokeratin (AE1/AE3), cytokeratin (CAM5.2), CK19, CD31, CD34, CD68, p63, S-100, Factor VIII, and desmin was all negative. The Ki-67 labeling index was almost 1%. A recurrent tumor was again detected in the site below the primary tumor at an 8-year follow-up, and it was surgically removed. The patient has had no symptoms of recurrence in 2 years after the second operation. CONCLUSION: The glomus tumor resorbed a bone and teeth roots when the tumor progressed into the mandible. The immunohistochemical features of the tumor were consistent with those described in previous reports. It is important to completely remove the Glomus tumor.

Does Intraoral Miniplate Fixation Have Good Postoperative Stability After Sagittal Splitting Ramus Osteotomy? Comparison With Intraoral Bicortical Screw Fixation.

PURPOSE: Bicortical screw fixation systems and miniplate with monocortical screw fixation systems have been reported mainly in bilateral sagittal split ramus osteotomy (BSSO). This study compared postoperative stability between these 2 fixation systems by an intraoral approach. MATERIALS AND METHODS: This was a retrospective cohort study. The study sample was composed of patients treated by BSSO at the authors' institute from January 2006 through December 2012. All cases had facial symmetry and were performed by setback surgery. The predictor variable was treatment group (intraoral screw fixation [SG] vs intraoral miniplate fixation [MG]), and the primary outcome variable was stability defined as the change in the position of point B. Other outcome variables were stability defined as the change in the position of the menton, blood loss, incidence of postoperative temporomandibular joint disorder, and nerve injury. Descriptive and bivariate statistics were computed and the P value was set at .05. RESULTS: Seventy-five patients (35 men and 40 women; mean age, 25.8 yr) were divided into 2 groups (39 SG cases and 36 MG cases). Postoperative changes at point B and the menton in the 2 fixation groups were not statistically different. Lingual nerve injury occurred only in SG cases. Moreover, total blood loss was greater in SG cases. CONCLUSION: An intraoral miniplate with monocortical screw fixation system is recommended over intraoral bicortical screw fixation for bone segments in setback BSSO in patients without facial asymmetry.

A case of hemangiopericytoma of the soft palate with articulate disorder and dysphagia.

We report a case of hemangiopericytoma of the soft palate of 60-year-old patient, who noticed a mass of the soft palate and experienced difficulty in speaking. We found a pediculate, hard, elastic mass measuring 38 mm (cross-sectional diameter). Computed tomography (CT) scans and dynamic magnetic resonance imaging (MRI) confirmed irregularly shaped mass and revealed a heterogeneous internal composition, consistent with vascular tumors. We excised the tumor under general anesthesia. Histopathological diagnosis was based on positive immunoreactivity of CD99 and vimentin and weak, positive staining of CD34. Three and half years following tumor excision, there is no recurrence or metastasis.

[Clinicopathological study of calcifying cystic odontogenic tumors].

Calcifying cystic odontogenic tumors are benign tumors, characterized by the presence of ghost cells and calcified materials. We evaluated clinical characteristics of calcifying cystic odontogenic tumors in 21 cases at the Maxillofacial Surgery, Tokyo Medical and Dental University Hospital, between January 1979 and December 2006. Of the 21 lesions that were studied, 12 were observed in male patients, and 9 in female patients. The median age was 13.0 years (range, 4-69 years). Of the 21 lesions, 11 were located in the maxilla (intraosseous), 9 in the mandible (intraosseous), and 1 in the lower gingiva (extraosseous). Radiographically, 18 lesions appeared as unilocular radiolucencies, and 2 lesions as multilocular radiolucencies. Impacted teeth were observed in 15 cases. In 20 cases, the lesions were treated by enucleation. The follow-up duration ranged from 2 years, 5 months to 28 years, 8 months, and in 1 case, the lesion recurred and showed a malignant transformation 2 years 10 months after the treatment. Histopathologically, the lining epithelium consisted of cuboidal or columnar odontogenic cells. Ghost cells were frequently calcified, and the tissue was hardened. In 14 cases, the tumor was associated with odontoma.

Tissue characterization of head and neck lesions using diffusion-weighted MR imaging with SPLICE.

PURPOSE: The purpose of this study was to evaluate the usefulness of diffusion-weighted (DW) MR imaging with split acquisition of fast spin-echo signals (SPLICE) in the tissue characterization of head and neck mass lesions. PATIENTS AND METHODS: DW MR images of 67 head and neck mass lesions were obtained using SPLICE with b-factors of 0 and 771s/mm(2). The lesions were classified into three categories: 16 cysts, 32 benign tumors, and 19 malignant tumors. After ADC maps were constructed for all lesions, ADC values were calculated and compared among the three categories. RESULTS: No case showed severe image distortion on DW MR imaging with SPLICE, and reliable ADC maps and ADC values were obtained in all cases. The mean ADC value of cysts was 2.41+/-0.48 x 10(-3)mm(2)/s, which was significantly higher than that of benign (1.48+/-0.62 x 10(-3)mm(2)/s) and malignant (1.23+/-0.45 x 10(-3)mm(2)/s) tumors (P<0.001). However, there was no significant difference between the ADC values of benign and malignant tumors (P=0.246). When an ADC value of 2.10 x 10(-3)mm(2)/s or higher was used as the diagnostic criterion for cysts, the sensitivity, specificity, and accuracy were 94%, 88%, and 90%, respectively. CONCLUSION: SPLICE was considered a recommended DW MR imaging technique for the head and neck. Although ADC values were useful in differentiating cysts from tumors, they contributed little in predicting malignancy.

Essential roles of Meltrin beta (ADAM19) in heart development.

Morphogenesis of the heart requires development of the endocardial cushion tissue that gives rise to the membranous septa and valves. Here we show that Meltrin beta/ADAM19, a novel metalloprotease-disintegrin, participates in the development of the endocardial cushion. Mice lacking Meltrin beta exhibit ventricular septal defect (VSD) and immature valves, and most of the animals die soon after birth. During development of the endocardial cushion, epithelial-mesenchymal transformation (EMT) of endocardial epithelial cells generates most of the cushion mesenchymes that constitute the main components of the septa and valves. Meltrin beta is expressed in both the epithelia and the mesenchymes of the endocardial cushion. In the absence of Meltrin beta, the cushion is small or thin in the septum-forming region and show poor remodeling of cardiac jelly components; both of these characteristics suggest impaired growth and differentiation of the endocardial cushion. When embryonic fibroblasts are cultured sparsely, Meltrin beta-lacking cells exhibit aberrant ectodomain shedding of type I Neuregulin, one of the ErbB ligands expressed in endocardial cells. These results suggest the necessity of proteolytic regulation of ErbB ligands by Meltrin beta for proper heart development.