Noriyuki Sakakibara

Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy.

To demonstrate appropriate treatment methods for mandibular osteoradionecrosis (ORN) by evaluating previous results.

Clinical value of genetically diagnosed lymph node micrometastasis for patients with oral squamous cell carcinoma.

The purpose of this study was to investigate the incidence and clinical significance of genetically diagnosed lymph node micrometastasis for patients with oral squamous cell carcinoma (SCC).

Inhibition of Na+,K+-ATPase by cisplatin and its recovery by 2-mercaptoethanol in human squamous cell carcinoma cells.

Na+,K+-ATPase (EC 3.6.1.37) is assumed to be involved in the transport of cisplatin [cis-diamminedichloroplatinum(II)] into cells and to act as a modulator of 5-fluorouracil (5-FU) in combination therapy of cisplatin and 5-FU. Whereas inhibition of Na+,K+-ATPase activity by cisplatin is expected to have effects on both anti-cancer therapy and nephrotoxicity, the inhibition mechanism remains to be elucidated. We studied the inhibition of Na+,K+-ATPase activity by cisplatin using an enzyme partially purified from Ca9-22 cells derived from a human squamous cell carcinoma of the gingiva. Cisplatin inhibited the Na+,K+-dependent ATP hydrolysis activity, and this inhibition depended on both the concentration of cisplatin and the preincubation time with cisplatin. The time-dependent inhibition was thought to be caused by a slow change of cisplatin from the inactive to the active form. We further tested the effect of cisplatin on the partial reactions of the enzyme, Na+-dependent ATP hydrolysis and K+-dependent pnitrophenylphosphate hydrolysis activities to determine which step in the reaction sequence of Na+,K+-ATPase was inhibited. Cisplatin inhibited both activities depending on its concentration and the preincubation time, whereas the Na+-dependent ATP hydrolysis activity was inhibited even at lower concentrations. Formation of a phosphointermediate of Na+,K+-ATPase was also inhibited by cisplatin depending on the concentration and preincubation time. Cisplatin (500 microM) and 8-fold higher concentration of 2-mercaptoethanol (2-ME; 4 mM) prevented inactivation of the enzyme by cisplatin, and the Na+,K+-ATPase activity inhibited by pretreatment with cisplatin was also recovered almost completely by 2-ME. These results suggest that the active form of cisplatin inhibits the Na+,K+-ATPase activity by inhibiting the formation of a phosphointermediate of the enzyme and that the inhibition by cisplatin is arrested by an addition of thiol group.

Cervical toxoplasmic lymphadenitis can mimic malignant lymphoma on FDG PET.

A 63-year-old woman presented with indolent swelling in her right submandibular region. CT and MRI demonstrated enlarge- ment of multiple right neck lymph nodes with homogeneous en- hancement. Because malignant lymphoma was suspected, whole body FDG PET was performed, which revealed accumulation of FDG in the submandibular region and additional increased accumu- lation with delayed imaging. After excisional biopsy of the enlarged right submandibular lymph node, histopathology showed evidence of probable toxoplasmic lymphadenitis. The patient had a history of exposure to cats and her serum toxoplasmic antibody titer was high. These findings led to a final diagnosis of toxoplasmosis. Increased uptake on FDG PET may occur in patients with cervical toxoplasmic lymphadenitis.

Osteoradionecrosis of the Mandible — Factors Influencing Severity

Abstract Objectives: To examine the factors influencing the severity of mandibular osteoradionecrosis to provide helpful data for the management of this condition. Patients and Methods: From 1963 to 1997, eighty seven patients with mandibular osteoradionecrosis who had received brachytherapy alone, combined radiotherapy and brachytherapy, or external radiotherapy alone were managed by conservative and/or surgical treatment. The time interval from completion of radiotherapy to the onset of osteoradionecrosis, the incidence of osteoradionecrosis with regard to the radiotherapy modality and the dose of external radiotherapy and brachytherapy used, and the factors involved in initiating osteoradionecrosis were examined. Results: There was a long term irreversible detrimental effect of irradiation. Most cases of osteoradionecrosis developed spontaneously within 36 months. External radiotherapy had greater detrimental effects on the development of osteoradionecrosis than did brachytherapy. When the onset of osteoradionecrosis was delayed and patients received a high dose of external irradiation, severe osteoradionecrosis developed. Conclusion: Conservative treatment or radical surgery should be selected for patients with osteoradionecrosis of the mandible by considering the previous radiotherapy modality and the time interval before the onset of osteoradionecrosis, as well as the dose of irradiation.

Distant metastases in patients with squamous cell carcinoma of oral cavity. Analysis of critical factors that influence development of distant metastasis with locoregional control.

口腔癌の遠隔転移発現に関与する因子を明らかにする目的で, 頸部転移様相をはじめとする臨床的・病理組織学的所見を検討した。1974年から1995年までに根治的治療を行った口腔扁平上皮癌535例中, 原発・頸部制御例は427例であった。頸部転移の有無で遠隔転移の発現率をみると頸部転移群では25/112 (22.3%) , 非転移群では5/315 (1.6%) で両群間に有意差がみられた (p<.001) 。このことより頸部転移群は遠隔転移のハイリスクグループであることが明らかとなった。今回ハイリスクグループである頸部転移群112例を対象に, さらに関連性の高い因子を検討すべく多重ロジスティック解析を行った。その結果, 転移リンパ節レベルのオッズ比が3.960と最も高く, レベルの進展した症例に対する遠隔転移の対策が必要と考えられた。