Brachytherapy is one of useful treatment modalities for early stage oral cancers. In Tokyo Medical and Dental University, it has been commenced since 1962. The number of cases per year is gradually increasing, and the total number reached approximately 3,000. In this review, I will present several oral （or tongue） cancer treatment cases, and discuss a current status and perspectives of brachytherapy for early stage oral cancer.
The Wnt/beta-catenin pathway plays a critical role in cell proliferation and oncogenesis. To clarify the role of cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma （SCC）, the cDNA of a mutant form of beta-catenin that lacks the entire region with the glycogen synthase kinase-3 beta （GSK-3 beta）-specific phosphorylation site was transfected into Ca9-22 cells whose beta-catenin had been expressed predominantly at the membrane, and permanent cell lines expressing aberrant beta-catenin in the cytoplasm and nucleus were produced. These transfectants, C1 and C5, proliferated at similar rates to the parental Ca9-22 cells, but the cell morphology changed from polygonal to spindle-shaped, and close cell-cell interaction was lost. These mutant betacatenin-expressing cells exhibited a significantly higher invasion/migration capacity than wild-type Ca9-22 cells. The transcriptional activities of this mutant beta-catenin form was enhanced in these cells, which could be demonstrated by an elevated level of the transcription factors T-cell factor （Tcf）/lymphoid enhancer factor （Lef）-dependent reporter gene activity, as well as by the up-regulation of Wnt/beta-catenin target gene matrix metalloproteinase （MMP）-7. Moreover, we observed the redistribution of E-cadherin, the rearrangement of actin filaments, and the elevation of active Rho family members, Cdc42 and Rac. These results suggest that aberrant cytoplasmic accumulation of beta-catenin can induce Tcf/Lef-mediated transcriptional activity, up-regulate MMP-7, and induce epithelial and mesenchymal transition （EMT）. This would enhance the invasion and migration of oral SCC cells.
Cancer/testis （CT） antigens are considered promising target molecules for immunotherapy for patients with various cancers.
To identify CT antigens or CT-like antigens, we performed serological identification of antigens by recombinant expression cloning （SEREX） analysis that screened a testicular cDNA library with serum obtained from a patient with gastric adenocarcinoma. We isolated 4 genes with testis specific profiles in the database, including G kinase anchoring protein 1 （GKAP1）. RT-PCR analysis showed that the mRNA expression levels of GKAP1 were restricted to the testis in normal adult tissues. In malignant tissues, GKAP1 was aberrantly expressed in a variety of cancers, particularly oral squamous cell carcinoma （OSCC）. mRNA expression analysis of other CT antigens revealed that MAGE-A4 was expressed in 32％, MAGE-A3 in 24％, MAGE-A1 in 13％, CCDC62-2 in 12％, SSX-2 in 11％, XAGE-1b in 7 ％, and NY-ESO-1 in 3 ％ of OSCC. 52.5％ of OSCC expressed at least one of these antigens. Of 15 sera from cancer patients with OSCC, 2 sera were reactive with GKAP1 protein on ELISA analysis. None of the healthy donor serum was reactive.
These findings suggested that GKAP1 is immunogenic in OSCC and demonstrated its potential as a diagnostic marker for patients with OSCC in combination with other CT antigens such as MAGE-A4, MAGE-A3, and CCDC62-2.
The resection range of malignant tumors of the lower lip is frequently extensive, and reconstruction using skin flaps becomes necessary. A successful outcome of reconstruction requires appropriate esthetics, food ingestion, and speech function. A 79-year-old man with a lower lip tumor was given a diagnosis of squamous cell papilloma as a result of a biopsy. Because malignancy was strongly suspected, total resection of the lower lip was performed under general anesthesia. Reconstruction was conducted using a skin flap, applying the Webster cheek advancement method. The features of this construction method are that the orbicularis oris muscles can be preserved, and since the suture line does not involve the mouth angle area, ruptured sutures are few. Furthermore, this method is advantageous in that postoperative recovery of lower lip function is rapid, surgery is completed in a single session, and the esthetic outcome is excellent. Although 3 years have passed since the surgery, no deformation or recurrence has occurred.
Epulis is an inflammatory or reactive hyperplasia of the gingiva, and commonly occurs in the oral region. However, epulis osteoplastica （peripheral ossifying fibroma） is a relatively rare disease. We report the case of a massive epulis osteoplastica covering the palate.
The patient was a 75-year-old woman who came to our clinic because of a palatal tumor. The tumor measured 60 × 50 × 20 mm and was elastical hard and pedunculated. A radiopaque area was found on radiographic examination. The clinical diagnosis was epulis osteoplastica, and gingival tumor excision was performed under general anesthesia. The histopathological diagnosis was peripheral ossifying fibroma （epulis osteoplastica）. As of 17 months after the operation, there has been no recurrence, and oral function is good.
We report the application of Mohs paste as a palliative treatment for a patient with facial and cervical skin metastatic carcinoma arising from uncontrolled oral cancer.
An 86-year-old man was referred to our hospital because of tenderness around the left molar region of the mandible. Squamous cell carcinoma of the left buccal mucosa with cervical lymph node metastasis （T2N2bM0） was diagnosed. We performed resection of the oral carcinoma with upper neck dissection. Four months after operation, metastatic masses on the facial and cervical skin appeared. We selected the palliative care because treatments such as surgical resection, adjuvant chemotherapy, and irradiation were contraindicated by advanced age, renal failure, and cerebrovascular disease. The metastatic skin lesion gradually became bigger; therefore we applied Mohs paste to control repeated bleeding and a malodorous discharge from the skin lesion. Bleeding and the malodorous discharge were controlled immediately after spreading the paste on the lesion, and the skin lesion was remarkably shrank day by day. Clinical application of Mohs paste for patients with skin metastatic lesions from oral cancer is a useful procedure for palliative care to improve their quality of life at terminal stage.