Relationship Between Mandibular Ramus Height and Masticatory Muscle Function in Patients With Unilateral Hemifacial Microsomia.

OBJECTIVE: To clarify the relationship between mandibular ramus height and function of masticatory muscles in patients with hemifacial microsomia. DESIGN: Retrospective study of imaging and physiological data. SETTING: Images and physiological data were obtained from the records of Sapporo Medical University Hospital. PATIENTS: A total of 29 patients with hemifacial microsomia who showed Pruzansky grades I, II deformity. MAIN OUTCOME MEASURES: Mandibular ramus height and masticatory muscle volume were evaluated with multi-detector row computed tomography. The electromyographic value was measured by the K7 Evaluation System. The hemifacial microsomia patients were classified into three groups based on the mandibular ramus height ratio of the affected and unaffected sides: group 0, >1.00; group 1, 1.00 to 0.85; group 2, <0.85. The Tukey-Kramer method and Games-Howell method were used to determine correlations between parameters. RESULTS: Decreased mandibular ramus height was significantly correlated with both reduced electromyographic values of the masseter muscle (P < .05) and the amount of mandibular lateral deviation at the time of maximum opening (P < .05) on the affected side. These differences were prominent in unilateral hemifacial microsomia patients classified as group 2. CONCLUSIONS: Decreased mandibular ramus height may cause dysfunction of the masseter muscles but not the temporal muscle on the affected side in patients with hemifacial microsomia.

Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. Previously we have identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) cytotoxic T lymphocytes (CTL). Survivin-2B80-88-specific CTL were induced efficiently from peripheral blood mononuclear cells (PBMC) of oral cancer patients after stimulation with the peptide in vitro. We conducted a phase I clinical study to evaluate the safety and the efficacy of survivin-2B80-88 peptide vaccination in HLA-A24-positive patients with advanced or recurrent oral cancer. The vaccines were given subcutaneously or intratumorally six times at 14-day intervals. Eleven patients were enrolled and 10 patients completed the vaccination protocol. No adverse events were observed in any patients. In two patients, the levels of serum squamous cell carcinoma (SCC) antigen decreased transiently during the period of vaccination. Tumor regression that was compatible with a partial response (PR) was noted in one patient. The remaining nine patients experienced progressive disease (PD). Immunologically, an increase of the peptide-specific CTL frequency was detected in six of the eight patients evaluated by HLA-A24/peptide tetramer analysis. The present clinical trial revealed that survivin-2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. However, subsequent clinical trials in combination with various adjuvant drugs will be required to improve the immunological and therapeutic efficacy. This trial was registered with University Hospital Medical Information Network (UMIN) number UMIN000000976.

[Clinical investigation of bisphosphonate-related osteonecrosis of the jaws].

We examined the clinical features of bisphosphonate(BP)-related osteonecrosis of the jaws(BRONJ), a serious complication resulting from intravenous BP treatment for multiple myeloma and malignant tumors with bone metastasis. We retrospectively reviewed the medical records of 36 patients who received intravenous BP therapy for the above-mentioned conditions, at Sapporo Medical University Hospital between July 2006 and October 2008. BP therapy caused BRONJ in 7 of 24 patients, but did not affect the bones of the other 17 patients. The other 12 of the 36 patients involved in the study were prescribed BP only after they had undergone an oral examination and treatment for dental inflammation. Of these patients, 7 developed BRONJ with BP treatment, after tooth extraction or acute dental inflammation. Treating dental inflammation before prescribing BP prevented the development of BRONJ. BRONJ is highly intractable and does not resolve with the standard treatment for osteomyelitis. Therefore, preventive therapy, which can be achieved by cooperation between medical doctors and dentists, is currently the most effective strategy for BRONJ. Conservative treatment with antibiotics may also be useful for maintaining or improving the quality of life of BRONJ patients.

[Osteomyelitis of the jaw in breast cancer patients receiving bisphosphonate therapy].

Osteonecrosis of the jaw is a severe new complication in cancer patients with bone metastases receiving bisphosphonate. Currently, there is no effective treatment for bisphosphonate-related osteonecrosis of the jaw, and the pathogenesis of this complication has not been completely elucidated. It has been shown that a potential risk factor for the complication is dentoalveolar trauma including extraction of teeth during bisphosphonate therapy. Attention should be paid to dental care in patients prior to the initiation of bisphosphonate therapy, and extraction of teeth during bisphosphonate therapy should be avoided to prevent this complication. Therefore, the communication between general physicians prescribing bisphosphonate and dentists is important.

A single-institute phase I/II trial combining nedaplatin dose escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma.

The purpose of this clinical trial was to assess the toxicity and efficacy of docetaxel plus nedaplatin induction chemotherapy in patients with locally advanced oral squamous cell carcinoma (OSCC). Twenty-one patients were enrolled in this phase I/II clinical study. The toxicities, response rates, and the maximum tolerated dose of nedaplatin that could be safely given preoperatively were assessed. Patients received escalating doses of nedaplatin (60, 70, 80, 90 mg/m2) combined with a fixed dose of docetaxel (60 mg/m2) on day one. Dose-limiting toxicity (DLT), grade 4 leukopenia lasting for two days or more, was seen in one patient at dose level 3; no other DLT was observed at any dose level. The overall response rate was 66.7%. The response rate was 100% at nedaplatin dose level 4, while that at dose level 1 was low (33.3%). Given these results, the recommended dose of nedaplatin in this regimen combined with fixed dose docetaxel (60 mg/m2) was determined to be 90 mg/m2. Docetaxel 60 mg/m2 plus nedaplatin 90 mg/m2 induction chemotherapy can be recommended for patients with locally advanced oral squamous cell carcinoma. Based on these results, an early phase II clinical study using this dose level was conducted; docetaxel plus nedaplatin induction chemotherapy appears to be a useful regimen for the treatment of OSCC. A late phase II clinical study is warranted.

Combined expression of p53, cyclin D1 and epidermal growth factor receptor improves estimation of prognosis in curatively resected oral cancer.

p53, cyclin D1 and epidermal growth factor receptor (EGFR) are molecular markers that regulate the cell cycle or cell growth and play important roles in tumor development and progression. In this study, we examined the impact of immunohistochemical expression of these markers on tumor progression in 140 oral cancers. p53, cyclin D1 and EGFR were expressed in 64 cases (46%), 54 cases (39%) and 54 cases (39%), respectively, but there was no inter-relationship between any two of these markers. In the association of these markers with clinicopathological features, EGFR expression alone was significantly associated with poor differentiation (P=0.0008) and invasive growth pattern (P=0.0003). Any of these markers, including EGFR, had no significant impact on survival. Coexpression of all these markers, however, was significantly associated with invasive growth pattern (P=0.0149) and shortened survival (P=0.0181), and was a significant and independent unfavorable prognostic factor (P=0.0002), along with tumor size (P=0.0040), nodal metastasis (P=0.0137) and growth pattern (P=0.0017) in a multivariate analysis. Simultaneous coexpression of these markers in oral cancers might prove to be a useful indicator for identification of low- or high-risk patients.