Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.

BACKGROUND: Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated. METHODS: COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis. RESULTS: No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival. CONCLUSION: Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.

Acute stress transiently activates macrophages and chemokines in cervical lymph nodes.

Acute restraint stress (RS) is routinely used to study the effects of psychological and/or physiological stress. We evaluated the impact of RS on cervical lymph nodes in rats at molecular and cellular levels. Male Sprague-Dawley rats were subjected to stress by immobilization for 30, 60, and 120 min (RS30, RS60, and RS120, respectively) and compared with rats of a no-stress control (C) group. The expression of genes encoding chemokines CXCL1/CXCL2 (Cxcl1 and Cxcl2) and their receptor CXCR2 (Cxcr2) was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and microarray analyses. Immunohistochemistry and in situ hybridization were performed to determine the expression of these proteins and the macrophage biomarker CD68. Microarray analysis revealed that the expression of 514 and 496 genes was upregulated and downregulated, respectively, in the RS30 group. Compared with the C group, the RS30 group exhibited a 23.0-, 13.0-, and 1.6-fold increase in Cxcl1, Cxcl2, and Cxcr2 expression. Gene Ontology analysis revealed the involvement of these three upregulated genes in the cytokine network, inflammation, and leukocyte chemotaxis and migration. RT-qPCR analysis indicated that the mRNA levels of Cxcl1 and Cxcl2 were significantly increased in the RS30 group but were reverted to normal levels in the RS60 and RS120 groups. Cxcr2 mRNA level was significantly increased in the RS30 and RS120 groups compared with that in the C group. RS-induced CXCL1-immunopositive cells corresponded to B/plasma cells, whereas CXCL2-immunopositive cells corresponded to endothelial cells of the high endothelial venules. Stress-induced CXCR2-immunopositive cells corresponded to macrophages. Psychological and/or physiological stress induces an acute stress response and formation of an immunoreactive microenvironment in cervical lymph nodes, with the CXCL1/CXCL2-CXCR2 axis being pivotal in the acute stress response.

Magnetic resonance imaging findings of sclerosing microcystic adenocarcinoma: A case report and review of the literature.

Sclerosing microcystic adenocarcinoma (SMA) is a rare malignant tumor of the salivary glands that closely resembles cutaneous microcystic adnexal carcinoma (MAC). It was newly listed in the 5th edition of the WHO classification of head and neck tumors. This report describes the case of a 61-year-old woman who presented with masses on the floor of the mouth. The masses showed low signal intensity on T2-weighted images (T2WI) and with low apparent diffusion coefficient (ADC) values. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) revealed a plateau or persistence after rapid initial enhancement. Histopathologically, the tumors comprised small infiltrating strands of cells that formed small ducts and cysts embedded in thick fibrous stroma, consistent with SMA. Low signal intensity on T2WI with a low ADC value and a plateau or persistence after rapid initial enhancement on DCE-MRI reflect the fibrous and cellular components of the tumor and can be considered characteristic MRI findings of SMA.

Postoperative evaluation of bone bridge after alveolar bone graft with cortical bone lining technique.

OBJECTIVE: For alveolar bone grafting (ABG), we have been performing surgery using a technique in which a cortical bone lining iliac endplate is applied to the anterior nasal aperture inferior margin. Herein, we used conventional and cortical bone lining techniques to examine the postoperative bone-bridge morphology after ABG. STUDY DESIGN: Fifty-five unilateral patients who underwent ABG at our clinic from October 2012 to March 2019 were included. We used postoperative CT data to compare the labiolingual width of the grafted bone and anterior-posterior and vertical shapes of the nasal aperture inferior margin with respect to the ungrafted side. RESULTS: The cortical bone lining technique was superior to the conventional method. The cortical bone lining technique showed good results regardless of alveolar cleft width or oral-nasal fistula. Also, tooth movement into the grafted area was involved in maintaining the residual graft bone; however, the cortical bone lining technique had better results. CONCLUSIONS: The cortical bone lining technique allows for the physical closure of nasolateral mucosal fistulas when it is technically difficult, and it can apply sufficient pressure to the bone marrow cancellous bone filling over the cortical plate bone. Our results illustrate the effectiveness of the cortical bone lining technique.

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.

Evaluation of patients with oral squamous cell carcinoma treated by radical irradiation with mold radiotherapy using a customized device: a retrospective clinical study.

BACKGROUND: It is very important to determine the indication of mold radiotherapy for the radical treatment of oral cancer. We investigated eight patients with oral squamous cell carcinoma who were treated by radical irradiation with mold radiotherapy using a customized device. METHODS: The subject is a case of curable superficial oral cancer of a few millimeters, or cancer of a size that can be cured by the placement of the radiation source. Of the eight patients, six were male and two were female, aged 64-93 years (mean, 78.9 years; median, 73.5 years). The primary sites were the buccal mucosa in three cases, gingiva in two cases, and floor of the mouth, soft palate, and lower lip in one case each. Five cases were in the T1 stage, and the remaining three cases were in T2. With respect to thickness, seven cases were of the superficial type and could not be detected by magnetic resonance imaging or computed tomography, and the remaining case showed a tumor thickness of 7.5 mm. All cases were diagnosed as squamous cell carcinoma by biopsy. Radical irradiation using mold radiotherapy was planned for all eight patients. Irradiation was delivered in 9-10 sessions, with a total dose of 45-50 Gy. RESULTS: Complete response was attained in six of the eight patients and partial response was observed in two patients, requiring additional treatment. CONCLUSION: Since all patients with complete response had superficial cancers, we hypothesized that superficial cancers of the oral cavity with thicknesses of few millimeters could be indicated for mold irradiation. This method can be applied in complicated cases and older patients in whom surgery or chemotherapy may not be feasible. We believe that the results of our clinical studies will be of great help in choosing this method.

General rules for clinical and pathological studies on oral cancer (2nd edition): a synopsis.

For doctors and other medical staff treating oral cancer, it is necessary to standardize the basic concepts and rules for oral cancer to achieve progress in its treatment, research, and diagnosis. Oral cancer is an integral part of head and neck cancer and is treated in accordance with the general rules for head and neck cancer. However, detailed rules based on the specific characteristics of oral cancer are essential. The objective of this article was to contribute to the development of the diagnosis, treatment, and research of oral cancer, based on the correct and useful medical information of clinical, surgical, pathological, and imaging findings accumulated from individual patients at various institutions. Our general rules were revised as the UICC was revised for the 8th edition and were published as the Japanese second edition in 2019. In this paper, the English edition of the "Rules" section is primarily presented.

Combination Laser Treatment With Real-Time Ultrasound Navigation for Oral Venous Malformations.

Vascular lesions, including hemangiomas and vascular malformations, are common benign diseases. More than 50% originate from blood vessels or vascular structures and are locate in the head and neck region. This study aimed to evaluate the efficiency and safety of a combination of laser treatments for oral venous malformations using ultrasound navigation. This study reports 3 cases of massive vascular malformation in the oral cavity, which were treated by a combination of a multiple spotted transmucosal irradiation technique (the so-called leopard technique) for the superficial layer, and intralesional photocoagulation for the deep layer using a neodymium-doped yttrium aluminum garnet laser, under real-time ultrasound navigation. All cases presented with a venous malformation with multiple blue swellings on the dorsum of the tongue, which had a maximum dimension of over 30 mm. The percent reduction in the size of the lesions was determined by magnetic resonance imaging. All cases showed a decrease in lesion volume of over 80%, without extensive tissue necrosis, 6 to 12 months after the laser treatment. None of the patients experienced any complications, and all were satisfied with the treatment outcome after one irradiation session.The results of this study suggest that laser treatment using ultrasound navigation is a promising approach for the safe and minimally invasive resolution of oral vascular lesions without scarring and loss of normal tissue architecture, sensation, oral function.

A modified preauricular and transmandibular approach for surgical management of osteosarcoma of the mandibular condyle within the masticator space and infratemporal fossa: a case report.

BACKGROUND: Osteosarcomas of the head and neck region are rare entities that comprise < 10% of all osteosarcomas. Multimodality treatment of patients with osteosarcoma is well-established for osteosarcoma in long bones, and the benefits of chemotherapy in long bones are clearly known. However, there is no consensus regarding the effects of chemotherapy in cases of head and neck osteosarcoma. The prognostic factor for head and neck osteosarcoma is complete tumor resection with negative margin, which is a radical surgery. However, a clear margin may be difficult to achieve in the head and neck region. CASE PRESENTATION: We present a case of a 69-year-old Japanese woman who developed osteosarcoma of the condyle within the masticator space and infratemporal fossa, which was treated with radical surgery using a modified preauricular and transmandibular approach. Although we recommended adjuvant treatment after surgery, the patient refused this treatment. There was no evidence of local recurrence or distant metastasis through 30 months of follow-up. CONCLUSIONS: Our modified preauricular and transmandibular approach allowed access to the masticator space and infratemporal fossa, thereby increasing complete resection of the tumor and resulting in minimal functional and cosmetic deficits.

A Multicenter Retrospective Study of Elective Neck Dissection for T1-2N0M0 Tongue Squamous Cell Carcinoma: Analysis Using Propensity Score-Matching.

BACKGROUND: This multicenter retrospective study aimed to determine whether elective neck dissection (END) can be performed for T1-2N0M0 tongue cancer. METHODS: Patients with T1-2N0M0 tongue squamous cell carcinoma who received treatment between January 2000 and December 2012 were enrolled at 14 multicenter study sites. The 5-year overall survival (OS) and 5-year disease-specific survival (DSS) were compared between the propensity score-matched END and observation (OBS) groups. RESULTS: The results showed that the OS rates among the 1234 enrolled patients were 85.5% in the END group and 90.2% in the OBS group (P = 0.182). The DSS rates were 87.0% in the END group and 94.3% in the OBS group (P = 0.003). Among the matched patients, the OS rates were 87.1% in the END group and 76.2% in the OBS group (P = 0.0051), and the respective DSS rates were 89.2% and 82.2% (P = 0.0335). CONCLUSION: This study showed that END is beneficial for T1-2N0M0 tongue cancer. However, END should be performed for patients with a tumor depth of 4-5 mm or more, which is the depth associated with a high rate of lymph node metastasis. The use of END should be carefully considered for both elderly and young patients.

Retrospective Study on Laser Treatment of Oral Vascular Lesions Using the "Leopard Technique": The Multiple Spot Irradiation Technique with a Single-Pulsed Wave.

OBJECTIVE: This study aimed to retrospectively evaluate the efficacy and safety of laser treatment of oral vascular lesions using the multiple spot irradiation technique with a single-pulsed wave. BACKGROUND DATA: In laser therapy for vascular lesions, heat accumulation induced by excessive irradiation can cause adverse events postoperatively, including ulcer formation, resultant scarring, and severe pain. To prevent heat accumulation and side effects, we have applied a multiple pulsed spot irradiation technique, the so-called "leopard technique" (LT) to oral vascular lesions. This approach was originally proposed for laser treatment of nevi. It can avoid thermal concentration at the same spot and spare the epithelium, which promotes smooth healing. The goal of the study was to evaluate this procedure and treatment outcomes. PATIENTS AND METHODS: The subjects were 46 patients with 47 oral vascular lesions treated with the LT using a Nd:YAG laser (1064 nm), including 24 thick lesions treated using a combination of the LT and intralesional photocoagulation. RESULTS: All treatment outcomes were satisfactory without serious complications such as deep ulcer formation, scarring, bleeding, or severe swelling. CONCLUSIONS: Laser therapy with the LT is a promising less-invasive treatment for oral vascular lesions.

Management of a Brain Abscess Presumably Caused by Radiation Osteomyelitis of the Mandible.

In this clinical report, we present the management of a brain abscess that was presumed to be caused by radiation osteomyelitis of the mandible. The patient underwent chemoradiotherapy for oropharyngeal carcinoma on the left side at the Department of Otolaryngology of our hospital in 2000. Local recurrence or metastasis did not occur post-treatment. In January 2009, the patient was diagnosed with radiation osteomyelitis of the mandible on the left side, complicated by a pathologic fracture. In July 2011, numbness occurred in the left upper extremity and the patient was transferred to the emergency center of our hospital. A computed tomography scan showed a tumor lesion in the brain that was diagnosed as a brain abscess by magnetic resonance imaging. Neurosurgeons performed burr hole drainage of the abscess, followed by administration of antibiotics. Although impaired fine movements of the left hand remain, progress has been relatively favorable with no recurrence of osteomyelitis or brain abscess post-surgery.

Influence of a dosing-time on toxicities induced by docetaxel, cisplatin and 5-fluorouracil in patients with oral squamous cell carcinoma; a cross-over pilot study.

Docetaxel, cisplatin plus fluorouracil (DCF) regimen is a useful chemotherapy, but is sometimes withdrawn due to severe adverse effects (AE). In this study, we examined whether the chronotherapy of DCF regimen could reduce the drugs-induced toxicities in clinical practice. Patients with oral squamous cell carcinoma were enrolled. Chemotherapy started at 10:30 (Morning-dosing) or 18:30 (Evening-dosing) for 5 days by a cross-over design. AE were assessed for 14 days after an initiation of each dosing. The grades of nausea, vomiting and neutropenia were smaller during Evening-dosing than during Morning-dosing. These data suggest that the chrono-chemotherapy might provide a merit for reducing the DCF regimen-related severe AE.

Free-flap surgical correction of facial deformity after anteromedial maxillectomy.

Anteromedial maxillectomy is typically performed in conjunction with low-dose radiotherapy and intraarterial chemotherapy. In doing so, the extent of surgical defects is reduced. However, nasal deviation and oral incompetence may ensue, due to cicatricial contracture of wounds, and may be distressing to these patients. Herein, we report a series of eight free perforator flap procedures (anterolateral thigh [ALT] flap, 6; thoracodorsal artery perforator [TAP] flap, 2) used to correct such deformities. The TAP flap was combined with scapular tip [ST] osseous flap in patients with added zygomatic prominence defects. Three adipocutaneous parts developed from each perforator flap were applied as follows: two to reconstruct nasal lining and oral vestibule, and one to augment cheek volume. All aesthetic results proved satisfactory, although orbital dystopia and contracture of mimic muscles were not resolved completely. These secondary interventions are suitable for sequelae of simple anteromedial maxillectomy. Immediate reconstruction should be considered if orbital floor and mimic muscles are involved.

Surgical Management of Duplication of the Pituitary Gland-Plus Syndrome With Epignathus, Cleft Palate, Duplication of Mandible, and Lobulated Tongue.

A 1-day-old male infant was referred to our department for evaluation of multiple malformations in his oral cavity. He was diagnosed duplication of the pituitary gland-plus syndrome with epignathus, cleft palate, duplication of the mandible, and a lobulated tongue. A thumb-sized mass lesion was visible on the hard palate. The duplicated mandible and lower lip was fused at the midline. The alveolar ridge was protruding through a wide-cleft soft palate involving the uvula. Further examination showed a lobulated tongue, which was seen behind the duplicated part of the mandible. Five days after birth, tracheotomy and epignathus resection were performed. At 7 months of age, the excess tissue of the duplicated mandible was resected at the area of adhesion on the lingual side, and the duplicated tongue and lip were reconstructed. A palatoplasty was performed at 20 months of age. Thereafter, the patient's progress was uneventful, with no abnormality in swallowing. No recurrence of epignathus has been observed during 2 years of follow-up.

Relationship Between Oral Perception and Habitual Chewing Side for Bare Bone Graft With Dental Implants After Mandibular Reconstruction.

OBJECTIVE: The purpose of this study was to investigate the relationship between habitual chewing side and perception of the oral mucosa following reconstruction with dental implants. STUDY DESIGN: Five patients comprised 2 males and 3 females, with ameloblastoma in 2 patients, odontogenic myxoma in 2 patients, and oral squamous cell carcinoma in 1 patient. They were treated using mandibular reconstruction with bare bone graft after segmental resection of the mandible. Perception (tactile, warm, and cold) was measured at 8 points (chin, lower lip, gingiva, and lateral edge of the tongue, bilaterally). Habitual chewing side was evaluated using a computerized index, the first chewing cycle, and a question on chewing. RESULTS: Perception on resected sides was improved at all measurement points for tactile and cold sensitive evaluation, although sensitivities on the resected side remained below the normal range. In the relationship between habitual chewing side and implanted prostheses in reconstructed bone, the chewing side was the resected side in 2 of the 5 patients. When those 2 patients underwent prosthesis implantation after removal of denture, the chewing side changed from the nonresected side to the resected side. Implant prostheses on resected side were suggested to contribute to masticatory function. Perception in those patients was incomplete but was improved compared with other patients. When prosthesis implantation is performed on the reconstructed side, the resected side may become the habitual chewing side. CONCLUSIONS: Recovery of perception can influence acquisition of the habitual chewing side.

Mandibular Reconstruction Based on the Concept of Double Arc Reconstruction.

The natural mandible has 2 arcs, the marginal arc and the occlusal arc. The marginal arc is situated along the lower margin of the mandible and affects the contour of the lower third of the face. The occlusal arc is situated along the dental arc and affects the stability of prosthodontics. The gap between these 2 arcs widens in the molar area. Our developed concept of "double arc reconstruction" involves making these 2 arcs for the reconstructed mandible. For the double-barrel fibula reconstruction, 2 bone segments are used to make both arcs. For reconstructions using the iliac crest, the double arc is made by inclination of the top of the bone graft toward the lingual side. Ten patients underwent double arc reconstruction: 2 underwent reconstruction with the double-barrel fibula, and 8 underwent reconstruction with the iliac crest. Four patients had a removable denture prosthesis, 1 had an osseointegrated dental implant, and 5 did not require further prosthodontic treatment. The shape of the reconstructed mandible after double arc reconstruction resembles the native mandible, and masticatory function is good with the use of a dental implant or removable denture prosthesis, or even without prosthodontics.

Detection of trace metallic elements in oral lichenoid contact lesions using SR-XRF, PIXE, and XAFS.

Oral lichen planus (OLP) and oral lichenoid contact lesions (OLCL) are chronic inflammatory mucocutaneous reactions with a risk of malignant transformation that alter the epithelium. OLP and OLCL have similar clinical and histopathological features and it is difficult to distinguish one from the other. Metallic restorations are suspected to generate OLCLs. Trace metal analysis of OLCL specimens may facilitate the discrimination of symptoms and identification of causative metallic restorations. The purpose of this study was to assess OLCL tissue samples for the prevalence of metallic elements derived from dental restorations, and to discriminate OLCL from OLP by using synchrotron radiation-excited X-ray fluorescence analysis (SR-XRF), particle-induced X-ray emission (PIXE), and X-ray absorption fine structure (XAFS). Typical elements of dental materials were detected in the OLCL, whereas no obvious element accumulation was detected in OLP and negative control specimens. The origin of the detected metallic elements was presumed to be dental alloys through erosion. Therefore, our findings support the feasibility of providing supporting information to distinguish OLCL from OLP by using elemental analysis.

[Reinforcement of warfarin action in a patient administered S-1].

A case showing reinforcement of the action of warfarin and potassium in a patient administered S-1 is reported.The patient was a 71-year-old man with left upper gingival cancer.He had ventricular tachycardia (VT), hypertrophic cardiomyopathy, and a cerebellar infarction.He underwent a pacemaker implantation, and was administered warfarin.After the operation, in mid-March 2010, he was administered with S-1 and warfarin. However, the international normalized ratio of prothrombin time (PT-INR) increased to an extremely high level of 5.82, and S-1 and warfarin were stopped. They were re-administered at the end of April, and the PT-INR stabilized to approximately 2.