Multi-institutional phase II trial of S-1 in patients with oral squamous cell carcinoma.

The aim of this study was to investigate the efficacy and safety of an oral fluoropyrimidine anticancer agent, S-1, in patients with oral squamous cell carcinoma. Patients with pathologically confirmed squamous cell carcinoma and at least one measurable lesion were enrolled. Oral administration of S-1 (40 mg/m2 twice daily) for 28 days was followed by a 14-day rest period. A total of 41 consecutive eligible patients were enrolled in the study between October 2002 and August 2004. The sites of the primary tumor were the gingiva (n=18), the tongue (n=12), the palate (n=5), the oral floor (n=4), the buccal mucosa (n=1), and the labial mucosa (n=1). A median of two cycles of treatment (range, 1-5) was administered. A complete response was achieved in nine patients and a partial response in eight patients, for an overall response rate of 41.5% (95% confidence interval, 26.4-56.5%). The 3-year survival rate was 76.4% (95% confidence interval, 62.8-90.0%). Although grade 3 anemia and anorexia occurred in two patients each (4.9%), and grade 3 neutropenia, thrombocytopenia, nausea, vomiting, stomatitis, and diarrhea in one patient each (2.4%), no grade 4 toxicities were observed. S-1 exhibits definite antitumor activity in patients with oral squamous cell carcinoma and is well tolerated.

Dental extractions in patients with cardiac sarcoidosis.

OBJECTIVES: To present data on hemodynamic changes during dental extractions in 5 patients with cardiac sarcoidosis, performed with electrocardiogram, heart rate, and blood pressure monitoring throughout the procedures, and to discuss the problems relating to the disease and dental extraction. METHOD AND MATERIALS: The medical data for 5 patients, including medical records, physician correspondence, and laboratory data before the treatments, were assessed. Seven dental extractions were then performed while monitoring and recording the hemodynamic conditions. Heart rate, blood pressure, rate pressure products, and electrocardiographic findings were analyzed. Finally, posttreatment evaluations of the general and local conditions of the patients were conducted. RESULTS: All dental extractions were performed in nonactive stable periods, with no remarkable hemodynamic changes or complications, while maintaining a stable hemodynamic state throughout the extraction procedure. All patients received a pretreatment supplement of corticosteroid. Wound healing was similar to that in normal patients under antibiotic prophylaxis against infection originating from the dental extraction wound and the original dental lesion. CONCLUSION: Pretreatment general evaluation of patients with cardiac sarcoidosis should be performed through various examinations and physician consultation, and a stable hemodynamic change during the surgical procedure should be maintained under any hemodynamic monitors. Corticosteroid supplement and antibiotic coverage are also necessary for safe dental extraction and suitable healing.

Fetal jaw movement affects development of articular disk in the temporomandibular joint.

Previous studies suggest that jaw movement is an important factor in the development of cartilage in the temporomandibular joint during the prenatal and postnatal periods. In the present study, the effects of fetal jaw movement on the articular disk were studied in mice by restraining the opening movement of the mouth using the mouse exo utero development system. At embryonic day 18.5, the articular disk was reduced in size in the embryos whose maxilla and mandible were sutured (sutured group) and there were changes in the cellular morphology of the mesenchymal cells in the disk. The volume of the articular disk, the total number of cells and the number of 5-bromo-2'-deoxyuridine-positive cells in the articular disk were significantly lower in the sutured group than in the non-sutured control group. Our data revealed that fetal jaw movement affects the development of the articular disk in the temporomandibular joint.

Development or existence of non-metastatic lymph nodes in the previously operated neck: a good prognostic sign for oromaxillary squamous cell carcinoma?

The aim of this study is to clarify the clinicopathological features of patients having non-metastatic lymph nodes in the previously operated neck for oromaxillary squamous cell carcinoma (OSCC). The clinicopathological factors of 9 such patients were comparatively analyzed with those of 78 other patients who underwent neck dissection (ND). The following observations were elicited from the data: (1) These 9 patients were alive and without OSCC for periods ranging from 1 year to 15 years and 9 months since their initial cancer treatments. (2) The interval between ND and clinical and/or imaging recognition of newly developed lymph nodes with suspicion of recurrence was significantly longer in these 9 patients. (3) The initially removed lymph nodes tended to be in a less advanced stage of disease. (4) Retrospectively, discrimination of non-metastatic lymph nodes from metastatic nodes was difficult in only one patient. (5) Each of the extirpated lymph nodes from 7 of the 9 patients showed a varying grade of reactive lymphadenitis on histopathology. In conclusion, the occurrence of benign hyperplastic lymph nodes in the previously operated neck region suggested favorable prognosis, though the immunological mechanism is not understood.

Evaluation of TS-1 based treatment and expression of thymidylate synthase and dihydropyrimidine dehydrogenase on oral squamous cell carcinoma.

Seventeen oral squamous cell carcinoma (SCC) patients underwent chemotherapy with TS-1 (8 males and 9 females, mean age; 75.1 years, range; 47-102 years). TS-1 permitted five cases of oral chemotherapy on an outpatient basis and 8 cases in elder patients over 80-years of age. Excepting five patients who underwent TS-1 therapy as post-operative adjuvant chemotherapy, the therapeutic efficacy of TS-1 in 12 patients with or without irradiation, surgery or chemotherapy resulted in 3 cases of complete response (CR), 6 cases of partial response (PR), 3 cases of stable disease (SD), with no progressive disease (PD) cases (overall response rate; 75%). SCC samples obtained from biopsy were immunohistochemically stained with anti-TS and DPD polyclonal antibody. Although the statistical significance was not clear, the expression of TS and DPD for CR cases was lower than that for SD cases. TS-1 therapy improved quality of life (QOL) especially in elder patients with oral SCC, and our immunohistochemical results suggested the predictive possibilities of TS and DPD expression in response to TS-1.

Etodolac, a selective cyclo-oxygenase-2 inhibitor, enhances carboplatin-induced apoptosis of human tongue carcinoma cells by down-regulation of FAP-1 expression.

The human tongue well-differentiated squamous carcinoma cell line, SCC-25, shows Fas-dependent apoptosis by treatment with carboplatin (CBDCA). FADD is markedly up-regulated by CBDCA, resulting in the induction of apoptosis. FAP-1, antiapoptotic tyrosine phosphatase, is expressed in the cytosol and blocks the transduction of the "death signal" from Fas to downstream. In this study, we show that etodolac, a selective cyclo-oxygenase-2 inhibitor, enhanced CBDCA-induced apoptosis of SCC-25, although etodolac alone did not induce the apoptosis. In combination with CBDCA, etodolac significantly decreased FAP-1 expression both at protein and mRNA levels, although etodolac by itself did not inhibit FAP-1 expression. These results indicate that etodolac, when combined with CBDCA, can enhance an action of anticancer drug through the suppression of FAP-1 expression.

[An advanced case of squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to chemotherapy with TS-1].

We report a case of advanced squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to oral chemotherapy with TS-1. The patient was an 89-year-old female with severe dementia. We carried out chemotherapy with TS-1 50 mg/day, without surgical treatment. The tumor disappeared clinically at 4 months after 3 courses of the TS-1 administration. Adverse drug reactions, including vomiting, leukopenia and thrombopenia, forced a stop of the administration of TS-1. Although she finally died of in senescence 2 months from the cease of administration, there was no recurrence of the cancer at the time.

Carboplatin induces Fas (APO-1/CD95)-dependent apoptosis of human tongue carcinoma cells: sensitization for apoptosis by upregulation of FADD expression.

We examined the apoptosis of tongue carcinoma cells and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA) induced apoptosis of SCC-9 and SCC-25, human well-differentiated tongue squamous carcinoma cell lines. Neutralizing anti-Fas (APO-1/CD95) and anti-Fas ligand (FasL) antibodies obliterated the CBDCA-induced cell death. In the absence of CBDCA, cytotoxic anti-Fas antibody, which binds to and activates Fas at the cell surface, failed to induce apoptosis. However, in the presence of CBDCA, the cytotoxic antibody markedly enhanced the apoptosis in a dose-dependent manner. Western blotting and reverse-transcription (RT) PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC-25 induced apoptosis of Jurkat cells, Fas-sensitive T-lymphatic leukemia cell line, and the apoptosis was inhibited by neutralizing anti-Fas or anti-FasL antibody. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional FasL, which by themselves fail to induce apoptosis. The expression of FADD in the tongue carcinoma cells was very low and was largely enhanced by CBDCA treatment. Suppression of FADD expression using the specific antisense oligonucleotide resulted in a failure of CBDCA induction of cell death. These results indicate that a deficiency of FADD is involved in the insensitivity of tongue carcinoma cells for Fas activation, and that CBDCA treatment switches nonfunctional Fas to functional Fas by upregulation of FADD expression, resulting in activation of a Fas-sensitive pathway leading to apoptosis.

Cardiac sarcoidosis: an overview of management for the patient requiring oral and maxillofacial surgery.

PURPOSE: The study goal was to present a current definition of sarcoidosis and an overview of cardiac involvement and implications in perioperative management of cardiac sarcoidosis. MATERIALS AND METHODS: Materials included a retrospective review of 4 patients with cardiac sarcoidosis who underwent minor oral surgery. Laboratory data, medical data, and data obtained through monitoring the patient's general condition related to the surgery were critically analyzed. RESULTS: Preoperative understanding of cardiac pathophysiology, evaluation of the patient's general condition, laboratory data, medical records, and physician correspondence were important, as was precise treatment planning against cardiac emergencies that could occur in surgical treatments. It was essential to monitor vital signs, any electrocardiographic changes, blood pressure, and heart rate, starting from the pretreatment period and continuing through the oral and maxillofacial surgery into the post-treatment period. Glucocorticosteroid coverage and prevention of endocarditis were also considered during oral and maxillofacial surgery planning. CONCLUSIONS: Critical issues were identified in the performance of oral and maxillofacial surgery for patients with cardiac sarcoidosis.

Clinical characteristics of oral adenosquamous carcinoma: report of a case and an analysis of the reported Japanese cases.

We present a case of adenosquamous carcinoma (ASC) which developed in the floor of the mouth of a 72-year-old Japanese man, and review 19 reported ASC cases in Japan from between 1986 and 2001, including the subject case herein. These ASCs occurred at an average age of 63 years, with 74% of the ASCs occurring in the floor of the mouth (8) and the tongue (6); the other sites of occurrence were the palate (3) and mandibular alveolus (2). Chief complaints were painless mass formation (28%), pain and/or sensational abnormality (28%), painful ulcer or swelling (22%), simple ulcer (11%), and miscellaneous others (11%). The clinical presentations of ASC were tumor with ulceration (58%), tumorous mass (26%), and ulcer (16%). Tumor size at first examination varied from bean-size to approximately 65 x 40 mm. In the pretreatment period, 31.3% were known to have cervical lymph node involvement, and descriptions on distant metastasis were not noted in any of the 19 cases. Some of the ASCs were initially diagnosed as other types of lesions, such as squamous cell carcinoma (SCC; 41%), adenocarcinoma (Ad.C; 12%) mucoepidermoid carcinoma (MEC; 6%), and MEC or SCC (6%). After initial treatments, neck and distant metastases were ascertained in 47.1 and 17.6% of the cases, respectively. Generally, a surgical procedure was performed as one of the most critical methods of treatment. The overall 5-year survival rate was 57.0%, with that of patients who underwent active treatment at 60.6%. Our study demonstrates the extent of the varied nature of ASC.