Hideaki Hirai

Sequential evaluation of swallowing function in patients with unilateral neck dissection

Neck dissection is the most reliable treatment for cervical lymph node metastases in head and neck cancer. However, it is unknown whether neck dissection can cause dysphagia. The aim of this study was to evaluate swallowing function after neck dissection.

Chronic mandibular osteomyelitis with suspected underlying synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: a case report

Chronic mandibular osteomyelitis is an intractable disease. In recent years, some case reports have related this disease process to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, which is chronic with frequent remissions and exacerbations. This report describes a case of chronic mandibular osteomyelitis suspected to be SAPHO syndrome. A 68-year-old woman presented with pain on the left side of the mandible. On the basis of clinical and radiological findings, chronic mandibular diffuse sclerosing osteomyelitis was initially diagnosed. We administrated oral clarithromycin (400 mg daily) and levofloxacin (500 mg daily), and her pain subsequently resolved. On 99mTc-labeled methylene diphosphonate scintigraphy, tracer uptake in the asymptomatic mandible was unchanged, but there was increasing tracer uptake in the sternocostal and sternoclavicular joints, compared with 99mTc-labeled methylene diphosphonate scintigraphic findings of the first visit. We diagnosed SAPHO syndrome and administrated oral sodium risedronate hydrate (2.5 mg daily). Although there has been no pain or swelling in the area of the left mandibular lesion, we have followed up on other skin and osteoarticular manifestations in conjunction with other medical departments.

NOTCH3 Is Induced in Cancer-Associated Fibroblasts and Promotes Angiogenesis in Oral Squamous Cell Carcinoma

Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs.

Clinical characteristics of multiple primary carcinomas of the oral cavity

OBJECTIVES This study aimed to clarify the clinical characteristics of multiple primary carcinomas of the oral cavity. MATERIALS AND METHODS We retrospectively reviewed the cases of 1015 patients who were treated during follow up for oral cancer at Tokyo Medical and Dental University between March 2001 and December 2012. We compared the clinical characteristics of 961 patients who developed single primary oral squamous cell carcinoma (SCC) during follow up and 54 patients who subsequently developed multiple primary carcinomas in the oral cavity. RESULTS Mean age at first diagnosis was significantly higher in patients with multiple primary carcinomas than single primary carcinoma. Multiple primary carcinomas showed a female predilection, were most prevalent in the gingiva, and tended to show earlier tumor and nodal stages than single primary carcinoma. The local recurrence rate was higher for multiple primary carcinomas than single primary carcinoma, and it increased with the number of multiple primary occurrences. The disease-specific survival rate at 10 years for patients with single primary carcinoma was 85.3% and that for patients with multiple primary carcinomas was 79.6%. The cumulative incidence rate for metachronous second multiple primary carcinomas after the onset of first carcinoma at 10 years was 8.0%. The recurrence of multiple primary carcinomas did not decrease the survival rate. CONCLUSION Differences were found in the clinical characteristics between patients with single oral SCC and those with multiple primary oral carcinomas. Early diagnosis and treatment as well as close long-term follow up are needed for patients with multiple primary oral carcinomas.

Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma

The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral cancer cells and fibroblasts, which are major cellular components of the tumor stroma, we conducted an in vitro study by using human oral squamous cell carcinoma (OSCC) cell lines and normal human dermal fibroblasts (NHDFs). The results of transwell assays revealed that the migration and invasion of 2 OSCC cell lines, HO1-N-1 and HSC3, were markedly stimulated upon coculturing with NHDFs. To investigate the factors that promote tumor invasion, we isolated NHDFs from cocultures prepared with HO1-N-1 cells and performed microarray analysis. Among the various genes that were upregulated, we identified the gene encoding leukemia inhibitory factor (LIF), and we focused on LIF in further analyses. We confirmed that all OSCC-derived conditioned media potently upregulated LIF expression in NHDFs, and the results of our transwell analysis demonstrated that NHDF-induced OSCC migration and invasion were inhibited by LIF-neutralizing antibodies. Furthermore, immunohistochemical analysis of patient samples revealed that in 44 out of 112 OSCC cases, LIF was expressed in the tumor stroma, particularly in cancer-associated fibroblasts (CAFs), and, notably, clinicopathological analyses confirmed that LIF expression in CAFs was significantly correlated with increased depth of tumor invasion. Collectively, our results suggest that OSCC stimulates fibroblasts to produce LIF, which, in turn, participates in cancer-cell invasion. Our finding offers a potential therapeutic strategy targeting the cancer stroma for the treatment of OSCC patients.

A case of basal cell adenocarcinoma of the upper gingiva

Basal cell adenocarcinoma arising from the minor salivary gland is extremely rare. We report a 76-year-old Japanese man with basal cell adenocarcinoma originating in the upper gingiva. He underwent subtotal maxillectomy combined with resection of the coronoid process, and reconstruction was performed using a rectus abdominis microvascular flap. The patient has been followed for 40 months after operation without any evidence of disease.

Appropriate surgical margin for odontogenic myxoma: a review of 12 cases

OBJECTIVE Odontogenic myxoma (OM) is a rare benign tumor that is frequently nonencapsulated and invades the surrounding bone, resulting in a high risk of recurrence. However, the optimal surgical technique and appropriate surgical margin remains controversial. Here, we report our clinical investigation of 12 patients with OM diagnosed histopathologically. STUDY DESIGN We retrospectively reviewed the records of 12 patients treated at our institution. Osteotomy or bone shaving with enucleation was generally performed with 5-mm bony margins from the radiologic extent of the tumor. RESULTS One half of the cases occurred in the maxilla and the other half in the mandible. Treatment for maxillary OM was enucleation in 2 patients and maxillectomy in 4 patients. Treatment for mandibular OM was enucleation with shaving of the surrounding bone in 1 patient and segmental mandibulectomy in 5 patients. Radiographs of surgical specimen removed by segmental mandibulectomy indicated that the mean distance between the tumor and the margin was 5.4 (range 3.4-7.0) mm. Tumor recurrence was noted in 1 patient who had undergone enucleation alone. CONCLUSION The 1-cm surgical margin for OM, as reported conventionally, might not be necessary. A prospective study is needed to determine the appropriate surgical margin for OM.

Value of real-time tissue elastography for squamous cell carcinoma of the tongue

Objectives: Real-time tissue elastography is an ultrasound tomography technique that can objectively display tissue elasticity. The aim of this study was to evaluate the strain ratio of tongue carcinoma and the normal tongue and to investigate how clinico-pathological factors influenced the strain ratio. We also investigated differences in the strain ratio between tumor and non-tumor tissue after preoperative chemo-radiotherapy. Materials and methods: Patients with tongue carcinoma were categorized into two groups: 38 patients who underwent surgery alone and who underwent preoperative elastography (group 1), and 12 patients who underwent elastography before and after preoperative chemo-radiotherapy (group 2). Results: The mean strain ratios in group 1 were 0.16 ± 0.13 in tumor tissue and 0.82 ± 0.35 in normal tissue. Statistical analysis revealed that the strain ratio of tumor significantly correlated with tumor thickness. In group 2, the mean strain ratio of tumor tissue, scar tissue, and normal tissue were 0.19 ± 0.18, 0.51 ± 0.28, and 0.77 ± 0.58, respectively. The mean strain ratio of scar tissue was 0.51 and had lower elasticity than tumor tissue and higher elasticity than normal tissue. Conclusions: It was useful to characterize the tissue distortion using the strain ratio. Additional studies to establish a cutoff value for tumor tissue might help expand the indications for limited surgery. Correspondence to: Hiroyuki Harada, Professor, Oral and Maxillofacial Surgery, Department of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan, Tel: +81-3-5803-5508, Fax: +81-3-5803-0199, E-mail: hiro-harada.osur@tmd.ac.jp Received: October 27, 2016; Accepted: November 04, 2016; Published: November 07, 2016 Introduction Preservation of function is important to preserve quality of life for patients undergoing treatment for oral cancer. The tongue is an essential organ for speech, food bolus formation and deglutition. Alternatively, this site is a good candidate for organ preservation techniques with the goal of preserving speech and swallowing function. Fortunately, preoperative chemo-radiotherapy has enabled many patients to avoid surgery and to improve cancer control with few side effects for patients with large unresectable cancers. These combined (chemo-radiotherapy) modality treatments lead to higher cure rates while maintaining the patient’s quality of life [1,2]. Indeed, advances in anticancer agent and radiotherapy have resulted in a potent antitumor effect in many patients. However, some patients treated with this strategy develop induration in the center of their tumor that histologically varies from viable tumor to scar tissue. If a determination could be made as to whether the remaining induration is tumor or scar tissue, it may be possible to establish criteria for limited resection versus no surgery [3-5]. Many diseases cause changes in the mechanical properties of tissues. The tissue flexibility is decreased by pathologic tissue changes, such as inflammation and tumor growth. Indeed cancer growth results in an increase in tissue stiffness, even during the early stages of cancer. Real-time tissue elastography is an ultrasound tomography modality that can objectively display tissue elasticity [6]. Basic principles including calculated method of strain ratio had been well described in the literature accompanied with a new guideline [7]. The strain distributions in tissues in response to external compression are closely related to the distribution of tissue elasticity. These strain images can give a clear illustration of underlying tissue stiffness and provides useful clinical information. Erastography is currently under investigation for diagnosing malignant breast tumor, thyroid tumor and cervical lymph node metastases [8,9]. However, there are no reports of its use in the evaluation of primary oral cancers. This method relies of the phenomenon in which compression of living tissue results in marked distortion of flexible tissues without affecting the shape of stiff tissues. When applying different levels of compression or relaxation, the elasticity imaging algorithm measures the displacement and strain by analyzing the RF (radiofrequency) signal in real time with subsequent conversion to a color-coded image. Using this method, the elasticity and strain ratio of squamous cell carcinoma of the tongue was measured, and the elasticity and strain ratio of the scar portion was quantified in cases in which preoperative therapy was performed [10]. Materials and methods Eligibility criteria The study was conducted between August 2011 and April 2015 in the Department of Oral and Maxillofacial Surgery of the Tokyo Medical and Dental University, Japan. All study protocols were approved by the institutional ethics committee (Approval number 729). All patients Aktar D (2016) Value of real-time tissue elastography for squamous cell carcinoma of the tongue Volume 2(6): 371-375 Dent Oral Craniofac Res, 2016 doi: 10.15761/DOCR.1000181 provided written informed consent before entry into this study. The subjects comprised 50 patients (38 men, 12 women; mean age, 59.1 years; age range, 30-86 years) who were treated for squamous cell carcinoma of tongue. Patients were categorized into two groups. Group 1 included 38 patients. These patients underwent surgery alone and elastography before glossectomy. Patients in group 1 underwent surgery for partial glossectomy (n=14) or for hemi-glossectomy (n=24). Group 2 included 12 patients who underwent elastography before and after preoperative chemo-radiotherapy. Patients in group 2 underwent surgery for hemiglossectomy (n=7) or for subtotal glossectomy (n=5). Preoperative therapies were chemoradiotherapy in 5 patients and chemotherapy in 7 patients. Preoperative chemoradiotherapy consisted of a total dose of S-1 at 65 mg/m2 per day for 5 consecutive days over 4 consecutive weeks with concomitant radiotherapy (40 Gy, provided at a fractional dose of 2 Gy for 5 days/week) in 4 patients. Preoperative chemotherapy consisted of a regimen of CDDP 80 mg/m2 (day 1) and 5-FU 800 mg/ m2 per day (days 1-5) plus a regimen of CDDP 60 mg/m2 and docetaxel 60 mg/m2 (day 1) and 5-FU 600 mg/m2 per day (days 1-5) for each one course plus 40 Gy of radiotherapy in one patient. Preoperative chemotherapy consisted of a regimen of CDDP 80 mg/m2 (day 1) and 5-FU 800 mg/m2 per day (days 1-5) for one course in 2 patient and for 2 courses in 2 patients. Preoperative chemotherapy consisted of a regimen of CDDP 60 mg/m2 and docetaxel 60 mg/m2 (day 1) and 5-FU 600 mg/m2 per day (days 1-5) for one course in one patient and for 2 courses in 2 patients. The median interval between end of preoperative treatment was 22.5 days (range, 13-35 days). T classification (group 1/ group 2) was T1: 6/0, T2: 26/4, T3: 6/8, and the N classification was N0: 30/3, N1: 4/1, N2b: 4/3 and N2c: 0/5. Histological classification of malignancy In group 1, the histological classification of malignancy was evaluated according to the multifactorial system proposed by Anneroth (Table 1) [11]. The histologic malignant score was determined using blocks of tissue that showed the maximum cross-sectional area. The number of mitoses was assessed by evaluating five random fields (magnification x400).