Correlation during the extent of surgical resection, oral function and quality of life after tongue cancer surgery: Single-institution study.

INTRODUCTION: The extent of surgical resection for tongue tumors is determined by tumor size, potentially affecting oral function and quality of life (QoL). However, the relationship between oral dysfunction and QoL decline due to glossectomy extent remains unexplored. Therefore, these correlations and their predictive value for postoperative QoL decline were elucidated. METHODS: Patients treated for tongue cancer at our hospital between 2018 and 2022 were categorized by partial, hemi, or subtotal/total glossectomy. Assessments included swallowing function (RSST), articulation (Oral Diadochokinesis (ODK)), mastication, tongue pressure, and oral moisture. QoL was measured using the Oral Health Impact Profile-14 (OHIP-14). Differences within parameters were assessed using Kruskal-Wallis tests, and between-group comparisons via Mann-Whitney U tests. Spearman's correlation analysis examined parameter relationship. RESULTS: 35 patients were evaluated. Significant differences were found in ODK [ta] (p = 0.015), [ka] (p = 0.0006), tongue pressure (p = 0.0001), moisture levels (p = 0.031), OHIP-14 domains: physical disability (p = 0.014) and social disability (p = 0.046). ODK [ta] (PG: 5.95, HG: 5.38, TG: 4.03 times), [ka] (PG: 5.56, HG: 4.78, TG: 3.23 times), and tongue pressure (PG: 32.9, HG: 21.2, TG: 10.3 mmHg) decreased with glossectomy extent, while physical (PG: 0.27, HG: 2.38, TG: 2.00) and social disability (PG: 0.18, HG: 0.94, TG: 1.43) worsened. A significant negative correlation was observed between tongue pressure and social disability (p = 0.013, r = -0.36). CONCLUSION: Expanding resection significantly impacted postoperative oral function and QoL. Tongue pressure assessment may predict long-term social disability in patient QoL.

Microvascular reconstruction for oral cancer in older adult patients: the impact of age on surgical outcomes.

OBJECTIVE: Flap complications continue to be a challenge in microsurgical reconstruction for older adults. We aimed to evaluate the impact of age on surgical outcomes after microvascular reconstruction. STUDY DESIGN: We retrospectively investigated 103 patients with oral squamous cell carcinoma who had undergone microvascular reconstruction surgery to compare microsurgical reconstruction, common postoperative complications, and flap success rates in geriatric (>75 years) and non-geriatric (<75 years) patients. We also evaluated differences based on the American Society of Anesthesiologists Physical Status score. RESULTS: We found no significant differences between the geriatric and non-geriatric groups in peri-operative, postoperative, or general complications. Conversely, we found that delirium and aspiration pneumonia were significantly more likely to occur in geriatric patients and that multiple medical complications were significantly more likely to occur in geriatric patients with a high American Society of Anesthesiologists score. CONCLUSION: Microvascular reconstruction can be performed effectively and without excessive complications in geriatric patients, and age should not be considered a contraindication for this procedure. Comorbidities play a stronger role in the prediction of adverse events.

Combination therapy of Mohs paste and chemotherapy improved metastatic oral cancer to the precordium skin and bilateral axillary lymph nodes: A case report.

Although Mohs paste can control bleeding, exudates, and odors from tumors, there have been no reports of the combination of Mohs paste with other treatments, such as chemotherapy, in oral cancer. Here, we report the combination of Mohs paste and chemotherapy for a case of metastatic oral cancer to the precordium skin and bilateral axillary lymph nodes. The tumors almost completely disappeared after the treatment. Combination therapy of Mohs paste and chemotherapy appears to have a better antitumor effect than Mohs paste alone.

Decreased prostasin expression is associated with aggressiveness of oral squamous cell carcinoma.

Prostasin is a glycosylphosphatidylinositol-anchored serine protease widely expressed in epithelial cells, with crucial epidermal barrier functions. Evidence has suggested prostasin may have served as a tumor suppressor in various cancers, but its role in oral squamous cell carcinoma (OSCC) remains unclear. Thus, herein, we conducted an immunohistochemical prostasin study in 119 resected OSCC cases. Prostasin expression was decreased in 63% (75/119) of cases. OSCC with decreased prostasin immunoreactivity (low prostasin cases) tended to show a higher histological grade (p = 0.0088) and a more infiltrative cancer cell morphology (p = 0.0024). We then explored the role of prostasin in the OSCC cell lines: SAS and HSC-4. SAS did not express detectable prostasin levels, whereas HSC-4 expressed low but distinct levels. Prostasin overexpression suppressed the proliferation and migration of both OSCC lines in vitro. Conversely, prostasin silencing significantly enhanced growth rates of HSC-4. Finally, we analyzed the impact of prostasin expression on the prognosis of patients with OSCC; decreased expression tended to correlate with shorter overall survival (p = 0.0291) after resection. This trend was supported by our analyses using a public database (Kaplan-Meier plotter) of head and neck squamous cell carcinomas. In conclusion, we showed decreased prostasin expression was associated with aggressive features and a poorer prognosis of OSCC.

Geranylgeraniol Induces PPARγ Expression and Enhances the Biological Effects of a PPARγ Agonist in Adipocyte Lineage Cells.

BACKGROUND: The global incidence of diabetes mellitus (DM) has risen precipitously, even in middle- and low-income countries. Peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in the control of cellular glucose metabolism. Activation of PPARγ beneficially results in increased insulin sensitivity. However, the expression of PPARγ is reduced by obesity and several nutritional factors. Here we examined the effect of geranylgeraniol (GGOH), a bioactive compound found naturally in fruits, vegetables, and grains, on the expression and activation of PPARγ. MATERIALS AND METHODS: C3H10T1/2 mouse embryonic fibroblasts and 3T3-L1 pre-adipocytes were used as in vitro models of adipocyte differentiation and function. Quantitative reverse-transcriptase polymerase chain reaction, western blotting, Oil Red O staining, and luciferase assay were performed to respectively assess mRNA expression, protein levels, lipid droplet formation and transcriptional activity. RESULTS: GGOH increased the expression of PPARγ in adipocyte lineage cells. GGOH also enhanced adipogenesis induced by rosiglitazone, a thiazolidinedione class PPARγ agonist. CONCLUSION: GGOH induces PPARγ expression and enhances the biological effects of a PPARγ agonist in adipocyte lineage cells.

IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression.

Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ.

OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. PATIENTS AND METHODS: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. RESULTS: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. CONCLUSIONS: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary. Key words:Bisphosphonate, osteonecrosis, jaw, prognostic, retrospective.

Evaluation of mandibular reconstruction with particulate cancellous bone marrow and titanium mesh after mandibular resection due to tumor surgery.

There are numerous treatment modalities for mandibular defects after tumor surgery. Autogenous particulate cancellous bone marrow graft combined with titanium mesh (PCBM-MESH) is an alternative procedure. The purpose of this study was to evaluate PCBM-MESH for mandibular reconstruction. There were a total of 10 cases from 2000 to 2011. Mandibles were successfully reconstructed in 9 cases; however, reconstruction failed in 1 case. Overall, the recovery of facial contours was excellent; conversely, the evaluation of prosthetic treatment varied widely. Thus, we suggest 3 steps for mandibular reconstruction: (1) recover the continuity of bone segments; (2) simulate optimum facial contours and dental occlusion; and (3) perform the occlusion with dental prostheses. PCBM-MESH is a valuable method for mandibular defects-particularly for restoring facial contours and a favorable alveolar ridge.

Prevalence and imaging characteristics of detectable tonsilloliths on 482 pairs of consecutive CT and panoramic radiographs.

BACKGROUND: Recent studies suggest that tonsilloliths are clinically related to halitosis and tonsillar abscess. Based on our empirical knowledge, tonsilloliths are relatively commonly encountered in daily clinical practice. It has been reported that the detection rate of tonsilloliths was under 24% in previous reports, although experience suggests otherwise. The purpose of the study was to evaluate the prevalence and characteristics of tonsilloliths using computed tomography (CT). In addition, the possible causes of low detection rates on panoramic radiographs were evaluated based on comparisons between CT images and panoramic radiographs in order to elucidate the limitations of visualizing the area around the palatine tonsils on panoramic radiographs. METHODS: 482 pairs of CT images and panoramic radiographs were retrospectively assessed with respect to the presence and characteristics of tonsilloliths. In addition, the causes in cases of disagreement between the two modalities were analyzed. RESULTS: The detection rate of tonsilloliths was 46.1% using CT scans, unlike previous reports. The characteristics of tonsillolith were dot-like figures with about 300-500 Hounsfield units within the palatine tonsil under the soft palate. The most common length of tonsilloliths was about 3 or 4 mm. As the subjects aged, the detection rate increased gradually. A significant difference in the tonsillolith detection rate was found between the over and under 40-year-old groups (p < 0.0001). However, the detection rate of tonsilloliths was only 7.3% on panoramic radiographs. A significant correlation was observed between the detection rate of tonsilloliths on panoramic radiographs and CT number (Spearman r = 0.429), size, (Spearman r = 0.318), and number of tonsilloliths (Spearman r = 0.333). CONCLUSION: The present results suggest that tonsilloliths are relatively more common than previously suggested. However, panoramic radiographs detect only a small percentage of palatine tonsilloliths. The low detection rates on panoramic radiographs might be related to the degree of calcification, size, and number of tonsilloliths.

Mechanisms involved in suppression of ADAMTS4 expression in synoviocytes by high molecular weight hyaluronic acid.

Aggrecan degradation is considered to play a key role in the progression of osteoarthritis (OA). Aggrecanases are members of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and degrade aggrecan in OA cartilage. The aim of this study was to clarify the mechanisms of expression of ADAMTS4 induced by IL-1ß in human fibroblast-like synoviocyte (HFLS) cells by high molecular weight hyaluronan (HMW-HA), a therapeutic agent used for OA. Monolayer cultures of HFLS cells were incubated with IL-1ß and HMW-HA. In some experiments, cells were pretreated with the CD44 function-blocking monoclonal antibody or inhibitors of signaling pathways prior to addition of IL-1ß and HMW-HA. The expressions of ADAMTS4 mRNA and protein were monitored using real-time RT-PCR, Western blotting, and immunofluorescence microscopy. To further determine the role of HMW-HA in IL-1ß-induced ADAMTS4 expression, activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), Akt, and NF-κB were analyzed by Western blotting. HMW-HA suppressed ADAMTS4 mRNA and protein expressions induced by IL-1ß. Pretreatment with the anti-CD44 monoclonal antibody recovered the inhibitory effect of HMW-HA on expression of ADAMTS4 mRNA induced by IL-1ß. Western blotting analysis revealed that IL-1ß-induced phosphorylation of p38 MAPK and JNK protein were diminished by HMW-HA. Furthermore, inhibition of the p38 MAPK and JNK pathways by chemical inhibitors suppressed ADAMTS4 mRNA expression stimulated by IL-1ß. These results suggest that HMW-HA plays an important role as a regulatory factor in synovial tissue inflammation.

Self-activated mesh device using shape memory alloy for periosteal expansion osteogenesis.

The present study evaluated the use of this self-activated shape memory alloy (SMA) device, with a focus on its effects in the region under the periosteum. Twelve Japanese white rabbits were used in this study. The device was inserted under the periosteum at the forehead. In the experimental group, the device was pushed, bent, and attached to the bone surface and fixed with a titanium screw. In control group, the device was only inserted under the periosteum. After 14 days, the screw was removed and the mesh was activated in the experimental group. Rabbits were sacrificed 5 and 8 weeks after the operation and newly formed bone was histologically and radiographically evaluated. The quantitative data by the area and the occupation of newly formed bone indicated that the experimental group had a higher volume of new bone than the control group at each consolidation period. Histologically, some newly formed bone was observed and most of the subperiosteal space underneath the device was filled with fibrous tissue, and a thin layer of immature bone was observed in the control group. In the experimental group, multiple dome-shaped bones, outlined by thin and scattered trabeculae, were clearly observed under the SMA mesh device. The use of self-activated devices for the periosteal expansion technique may make it possible to avoid donor site morbidity, trans-skin activation rods, any bone-cutting procedure, and the following intermittent activation procedure.

Clinical comparison between the retromandibular approach for reduction and fixation and endoscope-assisted open reduction and internal fixation for mandibular condyle fractures.

OBJECTIVE: Endoscope-assisted transoral open reduction and internal fixation (EAORIF) for mandibular condyle fractures has recently become popular because it is minimally invasive, provides excellent visibility without a large incision, and reduces surgical scarring and the risk of facial nerve injury. This report describes a retrospective clinical study that compared certain clinical parameters, including postoperative function, between the retromandibular (RM) approach and EAORIF. METHODS: Fifteen patients were treated by the RM approach, whereas 15 underwent EAORIF between July 2006 and September 2011 at Kyushu Dental College, Japan. Clinical indices comprised fracture line, fracture type, number of plates used, surgical duration, bleeding amount, and functional items, including maximum interincisal opening, mandibular deviation on the opening pathway, malocclusion, facial paresthesia, and temporomandibular joint pain and clicking. RESULTS: The areas subjected to either approach included lower neck and subcondyle. The RM approach was used for mandibular condyle fractures with dislocation of a small bone segment. Both groups used 2 plates in all cases. Surgical duration, maximum interincisal opening, mandibular deviation, occlusion, and temporomandibular joint function at 6 months after surgery were comparable between groups. The average bleeding amount in the EAORIF group was greater than in the RM group. One patient from the RM group developed facial paresthesia that persisted for 6 months after surgery. CONCLUSIONS: It was concluded that surgical treatment was suitable for fractures of the lower neck and subcondylar. Both procedures showed good results in the functional items of this study.

Pivot technique combined with mandibular backward distraction osteogenesis for the patient with high risk for relapse.

Severe skeletal relapse is one of the most difficult problems after mandibular advancement, and the management to overcome such problems tends to require more compromised methods and longer treatment period. We described that mandibular backward distraction osteogenesis with maxillomandibular fixation at an appropriate occlusion. Furthermore, to avoid inappropriate distraction vector, the distal plates of the distraction device were fixed with 1 screw to work as a pivot after the manipulation of the condyle to the glenoid fossa at the end of distraction activation. This technique was applied to 3 female patients with mandibular deficiency. The intraoral distractors were set on the lateral surface of the mandibular body; the fixation of the distal plate was fixed with 1 monocortical screw to make the proximal segment including the condyle manipulating at the end of the distraction phase by releasing the maxillomandibular fixation. The distraction rate was 1 mm/d, and the latency period was 7 days. The follow-up period after mandibular backward distraction osteogenesis ranged from 26 to 56 months. No specific complication, such as broken device, severe infection, or bony nonunion, occurred. Postoperative relapse was not observed during the follow-up period. This technique might become 1 choice to apply for mandibular deficiency in a patient with high risk for relapse.

Mechanisms involved in inhibition of chondrogenesis by activin-A.

OBJECTIVES: Activin-A, a member of the TGF-ß family, is known to be present in bone and cartilage. Although, involvement of the TGF-ß family in chondrogenesis has been reported, the mechanism by which activin-A regulates chondrogenesis has not been fully elucidated. The aim of this study was to investigate the effects of activin-A on chondrocyte differentiation in vitro. MATERIALS AND METHODS: Monolayer cultures of mouse chondrocyte ATDC cells were pretreated with a variety of inhibitors of major signaling pathways prior to addition of activin-A. The expressions of sox9, runx2, and osterix mRNA were detected using real-time PCR. To determine chondrocyte differentiation, sulfated glycosaminoglycans were stained with Alcian blue. To further elucidate the role of activin-A on chondrogenesis regulation, phosphorylation of Smad2/3, ERK, JNK, and Akt proteins was determined by western blotting. RESULTS: Activin-A suppressed the transcription of sox9, runx2, and osterix mRNA, as well as sulfated glycosaminoglycans accumulation. Activin-A also inhibited constitutive phosphorylation of JNK and Akt proteins. Furthermore, inhibition of the JNK and PI3K-Akt pathways by chemical inhibitors suppressed chondrogenesis in ATDC5 cells. CONCLUSIONS: These results indicate that activin-A may suppress chondrocyte differentiation in ATDC5 cells via down-regulation of JNK and Akt phosphorylation.

Risk factors for neurosensory disturbance after bilateral sagittal split osteotomy based on position of mandibular canal and morphology of mandibular angle.

PURPOSE: The aim of the present study was to evaluate the potential morphologic risk factors for postoperative neurosensory disturbance (NSD) after bilateral sagittal split osteotomy. PATIENTS AND METHODS: The study subjects were 30 skeletal Class III patients (9 males and 21 females), with a mean age of 22.0 years (range, 16-39 years). All patients underwent bilateral sagittal split osteotomy for setback to correct mandibular prognathism. The bone marrow space between the outer mandibular canal and the lateral cortex of the ramus was measured on transaxial computed tomography images, and the length at the mandibular angle between the retromolar and gonion was measured on the lateral cephalograms. The NSD was tested bilaterally using discrimination to touch with the sharp head of a mechanical probe. Each patient was evaluated at 1, 3, and 6 months postoperatively. RESULTS: The median bone marrow space was 1.96 mm (range, 0-4.5 mm), and median length of the mandibular angle was 30.93 mm (range, 23-37 mm). Neurosensory disturbance was present on 15 sides (25.0%) at 1 month postoperatively, 9 sides (15.0%) at 3 months postoperatively, and 7 sides (11.7%) at 6 months postoperatively. The difference in the incidence of NSD with a small bone marrow space and a long mandibular angle from that with a large bone marrow space and short mandibular angle was highly statistically significant (P = .006 and P < .01, respectively). CONCLUSIONS: The frequency of NSD after bilateral sagittal split osteotomy in Class III cases was dependent not only on the position of mandibular canal, but also on the length of the mandibular angle. A lateral course of the mandibular canal and a long mandibular angle appeared to result in a high risk of injury to the inferior alveolar nerve, resulting in NSD owing to a compromised splitting procedure.

Dual effects of heparin on BMP-2-induced osteogenic activity in MC3T3-E1 cells.

Heparin displays several types of biological activities by binding to various extracellular molecules, including pivotal roles in bone metabolism. We have previously reported that heparin competitively inhibits the binding activity of bone morphogenic protein-2 (BMP-2) to BMP and the BMP receptor (BMPR) and suppresses BMP-2 osteogenic activity. In the present study, we examined whether heparin affects osteoblast differentiation induced by BMP-2 at various time points in vitro. We found that 72 h of treatment with heparin inhibited alkaline phosphatase (ALP) activity. However, 144 h of treatment enhanced the ALP activity in BMP-2-stimulated MC3T3-E1 cells. Although heparin decreased the phosphorylation of Smad1/5/8 after 0.5 h of culture, prolonged periods of culture with heparin enhanced the Smad phosphorylation. In addition, 72 h of treatment with heparin enhanced the mRNA expression of runx2 and osterix in BMP-2-stimulated MC3T3-E1 cells. Furthermore, the mRNA expression of BMP antagonists and inhibitory Smads induced by BMP-2 was preferentially blocked by heparin at the 24 and 48 h time points. These findings indicate biphasic effects of heparin on BMP-2 activity and suggest that heparin has complex effects on the BMP-2 osteogenic bioactivities. Prolonged culture with heparin stimulated BMP-2-induced osteogenic activity via down-regulation of BMP-2 antagonists and inhibitory Smads.

Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts.

Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm(2)) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca(2+) pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca(2+) pathway.