[A clinical study of squamous cell carcinoma of the tongue base].

Between 1979 and 1992, 27 previously untreated patients with squamous cell carcinoma involving the base of the tongue underwent treatment with curative intent. Seven patients were in Stage I, II (26%) and 20 patients were in stage III, IV (74%). Seventeen patients (63%) presented clinically with neck metastasis. The patients were followed for a minimum of two years or until death or recurrence. Primary tumors treated with surgery or radiotherapy showed control rates of 80% (12 of 15 tumors) and 88% (7 of 8 tumors), respectively. The overall survival was 59 percent at 5 years. For the patients with exophitic primaries, local control with radiotherapy produced excellent results, whereas for advanced or deeply invasive tumors, surgery enhanced local control. Radiation therapy successfully controlled early neck disease (N0, N1). Patients with advanced neck disease (N2, N3) had poor regional control with radiotherapy, necessitating subsequent neck dissection. Forty-three percent of the N2b or N3 patients were found to have contralateral occult metastasis. Results obtained in the present study show that patients with T3, T4 or N2, N3 should undergo surgery. Prospective trials are necessary to compare surgery versus definitive radiotherapy with respect to patient survival and quality of life.

[Treatment of bilateral neck metastases in laryngeal cancer].

Laryngeal cancer is one of the most curable malignancies. One of the reasons is that most of them are in the early stage. However, the prognosis of advanced bilateral neck metastases is still poor. Based on loco-regional failure and cause of death, the effective procedure of neck dissection and the efficacy of postoperative irradiation were investigated retrospectively. A total of 1022 patients with laryngeal squamous cell carcinoma were registered in our hospital between 1979 and 1991, 58 of them (5.7%) had bilateral neck metastases. Clinical N2c cases accounted for 52% (32/58). In the other patients, the metastatic nodes were revealed by elective neck dissection for a clinically negative neck. The T stages of the 58 cases were as follows; T2 in 14 cases, T3 in 22 and T4 in 22. Forty-nine of the patients treated curatively by bilateral neck dissection were analyzed, 48 with total laryngectomy and 1 with partial laryngectomy. The remaining 9 patients were excluded because of radical irradiation in 3, distant metastases found the diagnosis in 3, unresectable recurrent neck metastases treated in other hospitals in 2 and no treatment because of severe myocardial infarction in 1. Cumulative crude and cause-specific 5-year survival rates for the 49 patients were 32.2% and 52.2%, respectively. Nineteen patients died of their disease; 10 of them of an uncontrolled neck lesion. From a comparison of the surgery alone group (28 cases) with a surgery plus irradiation group (21 cases) which consisted of preoperative irradiation in 2 and postoperative in 19, addition of irradiation may be effective for loco-regional control. Eight patients died of an uncontrolled neck lesion in the surgery alone group, while there were only 2 deaths in the postoperative irradiation group. Nevertheless there were no significant differences in survival: the cumulative crude and cause-specific 5-year survival rates in the surgery alone group were 34.4% and 56.2%, respectively, while those in the surgery plus irradiation group were 28.6% and 46.3%, respectively. It is obvious that the procedure of neck dissection influenced the loco-regional control. Excluding the recurrence-free patients who died of intercurrent diseases within 2 years, recurrence in the ipsilateral neck was found in 1 of 12 patients with radical neck dissection (RND), in 1 of 3 with modified radical neck dissection (MRND), in 2 of 15 with lateral neck dissection (lateral ND) and in 9 of 11 with regional neck dissection (regional ND). Recurrence is the contralateral neck were found in none of 2 with RND, of 3 with MRND and of 20 with lateral ND, but in 6 of 16 with regional ND. These results suggest that regional ND was insufficient to accomplish loco-regional control in those patients and that lateral ND or MRND or RND may be required bilaterally. Since 1986, all patients except 1 were treated by more extensive maneuvers than lateral ND bilaterally, so that loco-regional recurrence was found in only 1 case, in spite of the fact that the surgery alone group accounted for 73% (19/26). Cumulative crude and cause-specific 5-year survival rates for the patients prior to 1985 (23 cases) were 26.1% and 32.6%, respectively, while those for the patients since 1986 (26 cases) were 38.5% and 76.9%, respectively. There was no significant difference (p = 0.73) in cumulative crude 5-year survival rates between the 2 groups, but the difference in their cause-specific 5-year survival rates was statistically highly significant (p = 0.0032). It was concluded that lateral ND, MRND or RND should be required bilaterally for the patients with bilateral neck metastases and that addition of irradiation is not always indispensable for patients treated by curative neck dissection, such as lateral ND, MRND or RND.

Radiation therapy of the nasopharyngeal carcinoma. Treatment results and prognostic factors.

Between September 1977 and December 1989, 89 consecutive patients of nasopharyngeal carcinoma were treated with radiation therapy. The study comprised of 66 males and 23 females; their ages ranged from 17 to 80 years (mean 55 years). Five-year survival rates according to stage were as follows: stages I and II (n = 10), 90%; stage III (n = 10), 43%; stage IV (n = 69), 47%. The important prognostic factors for predicting poor prognostic in this series, which were shown by stepwise proportional hazard (Cox) model, were the level of lactate dehydrogenase (LDH) and neck node involvement. LDH level also influenced nodal failure (p = 0.0002) and distant metastasis (p = 0.006).

[Voice rehabilitation with esophageal speech in the laryngectomized].

From January 1988 to December 1990, 186 patients with laryngeal cancer or hypopharyngeal cancer underwent total laryngectomy in our hospital. We studied voice restoration in 110 of these patients by means of a direct interview method at the end of 1991. Seventy-six cases were excluded because of death (70) or being lost to follow-up (6). About 80% of the patients (89/110) attended esophageal speech classes, with a success rate of 78% (69/89). Seventy-four percent (51/69) had no problems with daily oral communication using esophageal speech. Neither radiation therapy nor post operative pharyngocutaneous fistula formation influenced the success rate. Neither did the site of the primary tumor in the larynx or hypopharynx exert an influence, although patients with laryngeal cancer were superior to those with hypopharyngeal cancer in terms of the quality of esophageal speech. It was found that age was the most important factor. Patients below 60 years old had a 90% success rate, between 60 and 75 the rate was 60% and above 75 it was only 10%. Unfortunately, 15% (17/110) of the laryngectomized patients used a pen and pad alone. Most were too old to attend esophageal speech classes.

[Multiple primary malignancies in patients with head and neck cancer].

From July, 1978 to December, 1985, 1,138 cases of malignancies of the head and neck were treated at the authors' hospital, and up to June, 1986, 132 patients with multiple primary malignancies were detected. In all cases, the incidence rate of a multiple primary malignancy was 11.6%. In 45 (33.0%) of these head and neck cancer cases, the multiple cancer was detected simultaneously, and as for the other cases (66.7%), they were discovered metachronously. In patients with a cancer of the mesopharynx, the incidence rate of a multiple primary malignancy was the highest (25.8%), whereas in those with a cancer of the parotid gland and in those with a cancer of the hypopharynx, the incidence rates were 20.0% and 14.9%, respectively. In most patients the second malignancy occurred in the same head and neck region, and in the rest, the second malignancy was a gastric cancer, a lung cancer, or an esophageal cancer in that descending order. Of the 45 synchronous cancer cases, ten were a thyroid cancer, most being latent. In head and neck malignancies, the authors stress the importance of a precise investigation prior to start of therapy and of maintaining follow-up investigations after therapy.

[Clinical analysis of supraglottic cancer].

We treated 159 cases of supraglottic cancer including 53 cases of transglottic type from July, 1978 to December, 1984. The mean age was 65 years and man to woman ratio was fifth. Of those patients 15 were classified as T1, 36 as T2, 56 as T3 and 52 as T4 and 113 as N0, 22 as N1, 14 as N2 and 10 as N3. Stage classifications were stage I in 13, stage II in 21, stage III in 50 and stage IV in 75. Treatment modalities were divided radiation in 25, operation only in 105, pre-or post-operative radiation in 29. Multiple primary malignancies were detected in 18 cases (11.3%). Until December, 1986, 52 patients died. Cause of death were original cancer (33 cases, 63.5%), additional malignancies (5 cases, 9.6%), intercurrent disease (12 cases, 23.1%) and others. Deaths of original cancer were attributable to the metastasis to the cervical lymph node and/or distant metastasis, mainly to the lung. Metastatic lymph nodes at the initial treatment were found in 66.7% of patients who died of supraglottic and/or transglottic cancer. In order to improve survival rates, early diagnosis and radical dissection of positive lymph nodes are seemed to be important.

[Cis-diamminedichloroplatinum (CDDP)-radiation therapy of an advanced nasopharyngeal carcinoma].

Between November 1983 and May 1985, 11 patients with locally advanced (stage IV) nasopharyngeal carcinoma were treated using a combination of Cis-diamminedichloroplatinum and radiation therapy (CDDP-RT group). In this group, 7 patients were given radical RT, sandwiched between 1 course of CDDP (70 mg/m2) before and 1 after. Four patients were given 1 course of CDDP prior to RT. Treatment results were compared with 32 patients (stage IV) who were treated with radiation therapy alone (RT group). These groups showed almost the same local control rate and distant relapses. There was no significant difference in the actuarial and relapse-free survival between the CDDP-RT group and the RT group. As a side effect, severe mucositis of the oral cavity was observed in 4 patients (36%) of the CDDP-RT group in contrast with 3 patients (9%) of the RT group (p less than 0.05).

[Local control after radiation therapy for T1N0M0 glottic carcinoma].

From 1978 through 1984, we had 151 patients with T1N0M0 glottic carcinoma. They were treated by radiotherapy with 4MV x-ray in parallel opposing field of 5 X 5 cm2 or 6 X 6 cm2. The total dose was 60 Gy/30 fractions/6 weeks. The local control rate was 88.1%, the local recurrence being noted in 18 cases (11.9%). Of these 18 cases, 6 underwent partial laryngectomy, and 10 total laryngectomy. The remaining two cases died: one refused further treatment for recurrence and the other died in spite of total laryngectomy due to recurrence after partial laryngectomy. The salvage rate was 94.1%. The cumulative survival rate was 82.6% in Tla, 71.5% in Tlb and 81.1% in 151 T1N0. The tumor response was poor in the presence of lesion occupying the whole length of the vocal cord. Also, in the cases with ulcer formation or thickened vocal cord as seen on laryngogram, local control rate was not good. Better results will be achieved by improving treatment techniques, specially by improving dose-distribution by wedge-filtered technique and method for immobilization in plastic shell during radio-therapy.

[A case of mesopharyngeal carcinoma that showed a complete response to induction chemotherapy].

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.

[Clinical studies of cancer of the mesopharynx].

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.

[Cis-diamminedichloroplatinum (CDDP)-radiation therapy in nasopharyngeal carcinoma].

Between July 1977 and October 1983, 40 patients with nasopharyngeal carcinoma were treated by radiation therapy. From the investigation of this series, prophylactic treatment for distant metastases was recommended for good prognosis. Between November 1983 and May 1985, 10 patients with nasopharyngeal carcinoma were treated using a combination of cis-diamminedichloroplatinum (CDDP) and radiation therapy. Treatment results showed complete response in all 10 patients. One patient failed in the out field of boost therapy after whole-neck irradiation. This patient has shown no distant metastases. The remaining 9 patients have been controlled well. Major side effects were renal toxicity, and nausea and vomiting, which were mostly transient. However, severe mucositis of the oral cavity was observed in 4 patients (40%) of the CDDP-radiation group in contrast with 3 patients (8%) of the radiation-therapy-only group (p less than 0.01).

[A case of hypopharyngeal carcinoma treated with multidisciplinary therapy without loss of the patient's voice].

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.

Multiple primary tumours in laryngeal cancer.

In a series of 1,389 cases of laryngeal cancer, multiple primary malignancies were found in 138 cases, 9.94 per cent. In these 138 patients, the most frequent sites of occurrence were the stomach and lung. Nine cases of triplicated malignancies and two cases of quadruplicate malignancies were found, and all died from the cancers. So-called radiation induced cancers were found in the 13 cases, showing a tendency toward field carcinogenesis or multicentric carcinogenesis. In 76 per cent of multiple primary tumours, the second or third tumour was the cause of death. The importance of inquiry regarding other malignancies in treatment and follow-up of laryngeal cancer was discussed. To obtain better survival of laryngeal cancer patients, early diagnosis and early treatment of the second primary tumours is essential.

[Acinic cell tumor of the epipharynx--a patient treated with surgery and high-dose intracavitary radiation therapy].

A case of acinic cell tumor of the epipharynx is reported. The patient was a 41-year-old man. The tumor was surgically removed by the transpalatal approach. Light microscopically, the lesion was composed of serous acinic cells with eosinophilic granules, clear cells with water-clear cytoplasm and their intermediate type, vacuolated cells. The serous acinic cells were PAS (periodic acid-Schiff)- and DPAS (PAS with diastase predigestion)-positive. The clear and vacuolated cells were PAS- and DPAS-negative. The patient underwent early postoperative radiation therapy; high-dose intracavitary radiation therapy using remote-controlled afterloading equipment was given subsequent to the external radiation therapy. The patient has been free of recurrence and abnormal findings for one year after treatment.

[A neo-adjuvant chemotherapy for carcinomas of the hypopharynx and cervical esophagus].

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.

Multiple primary tumors in patients with head and neck cancer.

From July 1978 to June 1984, 851 new cases of malignancies in the head and neck were registered in our hospital. Ninety-three patients with multiple primary tumors were observed. Triplicated malignancies were observed in three cases, i.e., larynx, thyroid, skin; stomach, tongue, larynx; and larynx, sarcoma, mesopharynx. The incidence rate was a high 30% in cancer of the mesopharynx (14/46), 14% in cancer of the larynx (55/392), and 7% in cancer of the hypopharynx. Additional primary malignancies occurred in the head and neck regions (25 cases), the digestive system (10 cases), the uro-reproductive system (18 cases), and others. Cancers of the stomach, lung, esophagus, and thyroid were predominant. Thirty-one cases (32.2%) were detected simultaneously and others were detected synchronously. We discuss the increased incidence rate of multiple primary tumors and the factors attributable to multiple primary tumors and stress the usefulness of systematic investigations.

[Borderline cases between the laryngeal and hypopharyngeal cancers].

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.