In this Part III Generalities, three important topics were described among clinical researches mainly focused on oral tumor and cancer so far performed during the past 38 years from 1965 to 2003 in Tokyo Medical and Dental Univ.and Oita Medical University etc.
As the first topic, the historical process of successful treatments for rpimary tongue cancer with 5-FU alone, an anti-tumor agent, and for oral mucous cancer with Bleomycin alone, an anti-tumor antbiotic were reported.
The second toipic concerned a first presentation of novel manipulations of plastic reconstruction, introduced to japanese oral surgery on the congress 1971 in Tokyo. The name of the novel manipulation was D-P skin flap, which was the simple and useful one among newly introduced plastic procedures through transplantation of skin-, muscle-flap and others. By means of these novel developed manipulations, we had succeeded to achieve adequate reconstruction after extended resection of oral cancer with resultant markedly improved outcomes. Among them, the first experience of D-P skin flap on the congress shown the death of the patient, although the result of the reconstruction could get success. On the report, it happened many discussions done and after that, because Shimizu found several important problems, then he persued the process of procedure by the operator. The anecdote had some historically interessant contents, so it was written, after listening to the related persons.
During the same period, a multi-drug conbined chemotherapy was widely performed for treating oral cancer also. The author recognized, unfortunately, that the therapeutic outcomes were rather negative and diasppointed.
The third topic was a therapeutic strategy for oral cancer patints, especially being aged and those with advanced tumor stages. By those cases, we should consider, how and where would be settled the limits and expectation for healing process and end results. The procedure and planning of their treatment must be different from those for the young or less advanced patients. Therefore the author emphasized that flexibility in selecting various combination of the therapeutic methods, according to each situation of the patients, hoping to let the patients get the better QOL and a prolonged peaceful coexistence with the tomor. This strategy was accepted on Japan Society of Clinical Oncology 2005.
The best treatment for oral cancer lies in the prophylactic procedure, removing the initiatiog and promoting factors of cancer formation. From the standing point, an important roll of smoking free has been recognized scientifically. As for oral cancer, the author had described a possible involvement of smoking in the pathogenesis of tongue cancer in his study in 1966, indicating the significance of preventing action against oral cancer by means of separated and/or abstained smoking.
As mentioned above, some criticized points still remain to be solved in the future as for how to consider the human span of life in relation to the existence of tumor, covering the life philosophy and ethics.
Finally, the author would like to conclude this article by saying that.
“only God is standing behind us and the God will follow the therapeutic course in patients with oral cancer.” likely as stated previously by a surgeon, Prof. Hans Killian, in Freiburg, German.

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A clinical study was made on the local status of 147 patients with oral squamous cell carcinoma who underwent surgery between 1999 and 2004. Local recurrence occurred in 10 patients (3/78 for tongue, 1/28 for mandibular gingiva, 1/16 for buccal mucosa, 1/9 for upper gingiva or hard palate, 2/7 for floor of the mouth, 0/9 for oropharynx, and 2/3 for central carcinoma of the mandible), and 2 patients finally died of local failure. The 5-year cumulative survival rate for 10 patients with local recurrence was low, being 40%, in contrast to 87.3% for 137 without local recurrence. These findings showed that most patients with oral cancer obtained local cure but the prognosis of those who had local recurrence was poor. The selection of operation methods at the initial therapy seemed to be important.

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Regional lymph node metastasis is closely related to the prognosis of squamous cell carcinoma of the oral cavity, and control of lymph node metastasis is an important therapeutic strategy. Therefore, microlymphatic movement is of concern in the primary lesion. However, there are many ambiguous points in that it can be difficult to distinguish between blood vessels and lymph vessels. This study was conducted in order to clarify the various relationships among angiogenesis, lymphangiogenesis, and tumor invasion in cancers of the oral cavity. Using a double stain of 5'-nucleotidase-alkaline phosphatase, blood and lymph vessel densities were measured simultaneously. Thereafter, the relationship between clinicopathological factors and blood and lymph vessel densities was investigated.
Results: 1) Blood and lymph vessel densities in normal mucosal epithelium were 27.4±4.4 and 12.8±4.0, respectively. On the other hand, those of cancer cases were 9.5±6.3 and 6.4±1.7, respectively. 2) Among the clinicopathological factors, T category, N category and grade of tumor differentiation did not correlate with blood and lymph vessel densities in metastatic or moderately to poorly differentiated cases. On the other hand, regarding the mode of invasion, the more diffuse the mode of invasion the higher the blood vessel density. However, the lymph vessel density was generally similar in each grade of mode of invasion with a slight increase in highly invasive carcinoma.

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This study evaluated the prognostic significance of the clinical growth pattern of squamous cell carcinoma (SCC) of the tongue. Two hundred six patients with surgically treated T1 and T2 tongue SCC were evaluated clinicopathologically. There were 114 males and 92 females who ranged in age from 21 to 85 years old. According to the UICC classification (1997), there were 106 patients classified as T1 and 100 as T2. One hundred sixty-three patients were classified as N0, and 43 patients had clinically positive nodes. Based on the surgeon's close inspection and digital palpation at the primary site, clinical growth pattern was classified into three types: superficial, exophytic and endophytic. Superficial tumor is an erythroplakic or leukoplakic lesion lacking deep induration. Exophytic tumor is a papillary or granular lesion with moderately deep induration. Endophytic tumor is an ulcerative or indurative lesion with extensive deep induration.Thus, tumors were classified into 51 (24.8%) of the superficial type, 37 (18.0 %) of the exophytic type, and 118 (57.3%) of the endophytic type.
Almost all superficial tumors were 5 mm or less in thickness and were accompanied with pericancerous epithelial dysplasia on histologic sections. On the other hand, endophytic tumors were more likely to infiltrate diffusely into the deep portion. Exophytic tumors showed intermediate malignancy between the superficial type and endophytic type. Local recurrence was most likely to occur in superficial tumors correlating with the presence of pericancerous epithelial dysplasia. Neck metastasis was developed in 3.9% of superficial tumors, 16.2% of exophyic tumors, and 56.5% of endophytic tumors. The clinical growth pattern was a significant indication for predicting neck metastasis. Five-year cause-specific cumulative survival rates were 100.0% in the superficial type, 90.5% in the exophytic type, and 80.6% in the endophytic type (p<0.01) . Thus, clinical growth pattern is a simple and useful classification to grade malignancy of early tongue SCCs.

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