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A 55-year-old male with a mesopharyngeal carcinoma (squamous cell carcinoma) T3N3N0 and a pulmonary carcinoma (adenocarcinoma) T3N2M0 was treated with induction chemotherapy, consisting of cisplatin (100 mg/body), bleomycin (30 mg/body), and methotrexate (40 mg/body), that was followed by a radical neck dissection of the cervical metastatic lesion. After two courses of chemotherapy, both the primary and nodal lesions of the mesopharyngeal carcinoma showed a complete response and, histologically, no evidence of any viable tumor cells remained. The patient died, however, due to the pulmonary carcinoma two years and seven months after his first treatment. An autopsy revealed no evidence of the squamous cell carcinoma. In this case, the squamous cell carcinoma of the mesopharynx and the cervical lymph nodes showed a radically good response to treatment by chemotherapy.

A 53-year-old man under a diagnosis of piriform sinus carcinoma T 3 N 1 was treated with neoadjuvant chemotherapy consisting of cisplatin (70 mg/m2) and peplomycin (5 mg/day X 10), followed by radical neck dissection and radiotherapy to the primary site and whole neck. After two courses of chemotherapy, the primary tumor showed complete response and nodal metastasis showed partial response. After discharge, the patient has shown no evidence of disease. Hypopharyngeal carcinoma was controlled with neoadjuvant chemotherapy and radiotherapy without the patient's voice being lost, since chemotherapy as the initial treatment was very effective in reduction of the tumor bulk and did not damage the blood circulation.

Between July, 1978 and December, 1981, we treated 215 patients with laryngeal cancer and 57 patients with hypopharyngeal cancer. The former exhibited good, latter poor, prognoses. Ten patients required a differential diagnosis between supraglottic lesion and pyriform sinus lesion. The initial symptoms, habits of smoking and drinking, sputum cytology, laryngo-tomography and contrast laryngograms which may contribute important information such as failure of the pyriform sinuses to fill, aid in establishing the site of origin of the primary tumor preoperatively. Tumors originating in the pyriform sinus should be operated, paying attention to the mesopharyngeal margin and multicentric carcinogenesis. We also discuss preoperative irradiation, neck dissection and chemotherapy.

The incidence of cancer of mesopharynx is not so high in Japan. Age-standardized incidence rates per 100,000 population of this tumor is 0.2 (0.4 in male, 0.1 in female) in Japan. The mesopharyngeal tumors contain three types: squamous cell carcinoma from squamous epithelium, malignant lymphoma from Waldeyer's tonsillar ring and adenocarcinoma from minor salivary glands. The squamous cell carcinoma is most frequent in patients between the ages of 50 and 70 years, males being affected 5-10 times as frequently as females. Epidermiologically, cancerization of mesopharynx is dependent on heavy smoking and drinking. Because of the high incidence of regional neck node metastases at initial examination, combined therapy with radiotherapy, adjuvant chemotherapy, composite operation and reconstructive surgery must be done in co-operation with surgeon and radiation therapist, working as a team. Survival rates of this tumor are 30-40%.

Neo-adjuvant chemotherapy, followed by definitive surgery and/or radiotherapy was utilized in nine patients with carcinoma of the hypopharynx and cervical esophagus starting in December, 1983. They were treated with combination chemotherapies which included CDDP, PEP (BLM), and MTX. The patients' ages ranged from 52 to 70 years with an average of 57. The histologic types were all squamous cell carcinoma and performance status was 1 in all cases. There were 7 stage III and 2 stage IV. Of 9 patients, 3 showed complete response and 6 showed partial response of the primary tumor with an overall response rate of 100%. Of 8 patients, 3 showed complete response and 2 showed partial response of the metastatic node with an overall response rate of 62.5%. Toxic effects included alopecia in 9 patients, nausea/vomiting in 7, eczema in 4, RBC below 350 X 10(4)/mm3 in 5, WBC below 3000/mm3 in 1, peak serum creatinine above 2 mg/dl in 1. All patients except one with renal toxicity were able to start definitive treatment soon after chemotherapy, the primary and regional lesions being subsequently well controlled in all 9 patients. Neo-adjuvant chemotherapy appears to be very effective for the reduction of tumor bulk. This multidisciplinary therapy should be expected to increase survival rate.

Between 1978 and 1983, ninety-three patients with cancer of the hypopharynx were treated. They were evaluated as to sex, age, primary site, TNM classification, stage, habits of smoking and drinking, past history of irradiation, treatment modality and end results. Eighty-seven percent of the patients visited us at as late a stage as advanced stage III or IV, and were treated mainly by combined therapy involving irradiation and pharyngolaryngoesophagectomy. The 3-year and 5-year survival rates were 38.6% and 33.3%, respectively. After December 1983, 14 new patients with advanced disease including three with coervical esophageal cancer were treated with neo-adjuvant combination chemotherapy which included cisplatin, peplomycin, methotrexate, and bleomycin over two courses of therapy. The response rate (CR + PR) was high, being 82% for the primary tumor and 78% for the metastatic node. Histopathological effects of neo-adjuvant chemotherapy were studied in the resected specimens. The evaluation was based on the Ohboshi-Shimosato classification. The histological effects did not agree with the clinical effects. Grade II b change was evaluated mostly in CR cases and grade II a change was seen in PR cases. It thus seems that neo-adjuvant chemotherapy prior to surgery and/or radiation including cisplatin and other agents is very useful as a multidisciplinary treatment for cancer of the hypopharynx.

From January, 1978 to December, 1984 fifty four cases of cancer of the mesopharynx were registered at our clinic. There were 47 males and 7 females. Age distribution was from 18 to 80 years old with a mean age of 59. Site distributions were 32 in the lateral wall, 11 in the superior wall, 3 in the anterior wall and 2 in the posterior wall. The Brinkman index for smoking habits and to alcohol index for drinking habits were 488.3 and 20.8 respectively, which were significantly higher than for the control group (p less than 0.05). Pathohistological diagnosis was squamous cell carcinoma in 46 cases, adenocarcinoma in 3 cases, anaplastic carcinoma in 3 cases, and 4 others. Secondary malignancies were highly developed in 15 cases (27.8%), including cancer of the larynx (5), esophagus (3), stomach (2) and others (5). Stage classification was stage I in 3 cases, stage II in 13 cases, stage III in 16 cases and stage IV in 22 cases. Of 47 cases, 39 cases were treated by radiation, 5 cases by operation and 2 cases by pre-radiation chemotherapy. The local control and absolute survival rates for T1-T2, N0-N1 lesions were quite good. Advanced local and nodal disease proved difficult to control with radiation alone. Three and five-year survival rates were both 37.0%. It is suggested that heavy drinking is one of the probable etiologic factors in cancer of the mesopharynx. Intensive follow-up is necessary to detect second primary cancers. For better results, multi-disciplinary treatment should be explored.

From October 1977 through December 1983, 61 patients with carcinoma of the hypopharynx were treated with radiation therapy (RT) and surgery or with RT alone. Five-year survival rates by N-stage, according to the TNM classification by UICC (1978), were 52% for N0 cases, 23% for N1, and 17% for N2-3 (N1 vs. N2-3, not significant). For N1-3 cases, corresponding figures by level of cervical nodal involvement by UICC (1978) were 29% for level 3 cases, 15% for level 2, and 8% for level 4 (level 3 vs. level 4, p less than 0.04). Therefore, the level of cervical nodal involvement was a more useful prognosticator for patients with nodal metastasis than the N-stage. Effective nodal control for patients with clinically positive nodes (N1-3) was obtained with a combination of neck node dissection and RT of 50 Gy or more. For N0 cases, elective RT of 50 Gy or more, encompassing an adequate field, was required.