Tomoho Maeda

Changes in the Ki-67 Labeling Rates of Head and Neck Squamous Cell Carcinomas during Preoperative Radiation Therapy

Immunostaining with Ki-67 monoclonal antibody was performed on frozen sections of biopsy specimens obtained before and during preoperative radiation therapy from 21 patients with head and neck squamous cell carcinoma. The Ki-67 labeling rates before radiation therapy and at radiation doses of 10 and 20 Gy ranged from 21 to 71% (mean: 35.0%), from 7 to 49% (mean: 25.8%) and from 1 to 44% (mean: 14.8%), respectively. One of the 2 patients whose tumors showing Ki-67 labeling rates of greater than 48% (mean +1 SD) before radiation therapy suffered local relapse shortly after the treatment. Moreover, tumors with rapidly decreased Ki-67 labeling rates (lower than 3%) at radiation doses of 20 Gy were related to poor clinical outcome: 4 out of 6 patients whose tumors showed Ki-67 labeling rates below 3% (mean -1 SD) at 20 Gy of irradiation had local relapses or showed distant metastases. These findings indicate that immunostaining with Ki-67 monoclonal antibody of biopsy specimens of head and neck squamous cell carcinoma, before and during radiation therapy, is very useful in assessing the clinical outcome of the patients.

Immunohistochemical Study of Mononuclear Cell Infiltrates in Squamous Cell Carcinoma of Oral Cavity and Paranasal Sinus

Serial frozen sections were prepared from 22 squamous cell carcinomas of oral cavity and paranasal sinus. Mononuclear cell infiltrates were stained by the biotin-avidin-horseradish peroxidase method using a panel of 10 mouse monoclonal antibodies to human leukocyte antigens. The degree of infiltration was graded from + + + (marked) to - (absent). The infiltration of anti-Leu-4-reactive cells (Leu-4+ cells) was grade + + or + + + in 14 of 22 cases. In 13 of 22 cases, infiltration of Leu-3a + 3b+ cells (helper/inducer T lymphocytes) was grade + + (moderate). In 5 of 20 cases, infiltration of Leu-2a+ cells (cytotoxic/suppressor T lymphocytes) was grade + +. As for B lymphocytes, infiltration of Leu-12+ cells was grade + + in only 2 of 19 cases. In conclusion, T lymphocyte infiltrates were commonly seen in squamous cell carcinoma in oral cavity and paranasal sinus and the number of patients with grade + + infiltration of helper/inducer T lymphocytes significantly predominated over that of patients with infiltration of cytotoxic/suppressor T lymphocytes grade + +.

Changes in Peripheral Lymphocyte Subsets during Radiotherapy for Lung Cancer Patients

In order to better understand the immunologic effects of irradiation, blood levels of lymphocyte subsets were sequentially monitored in 37 patients before and during irradiation treatment for lung cancer. During irradiation, the peripheral blood levels of each T cell subgroup, OKT3-reactive (OKT3+), OKT4+, OKT8+ and OKT11+ lymphocytes showed similar radiosensitivity. No selective depletion of either OKT4+ or OKT8+ lymphocytes was seen. The levels of OKT6+ and OKT9+ lymphocytes were different depending on the case. At the end of irradiation, the percent of lymphocytes bearing the OKT10 antigen increased significantly. As to OKM1+ and OKIa1+ lymphocytes, the levels were almost consistent but showed a rather big standard deviation.

Infiltration of Leu-3a+3b-positive lymphocytes and expression of human leukocyte antigen DR on tumor tissue induced by radiation therapy.

Tumor infiltrating lymphocytes induced by radiotherapy were analyzed by the biotin-avidin-horseradish peroxidase method. At the early dose of 4 Gy (400 rad) of irradiation (2 Gy X 2), remarkable infiltration of lymphocytes was observed surrounding cancer cells. This infiltration was mainly composed of Leu-3a+3b-positive lymphocytes, and human leukocyte antigen DR-positive tumor and interstitial cells were remarkably observed.

Application of the Immunohistochemical Method as a Predictive Assay in Radiotherapy of Squamous Cell Carcinoma of Oropharynx and Hypopharynx

We analyzed various subsets of lymphocytes infiltrated into cancer tissues from 15 patients (10 cases of oropharyngeal cancer and 5 of hypopharyngeal cancer) before treatment and after irradiation with approximately 10 Gy (1,000 rad) and 30 Gy by the method of biotin-avidin-horseradish peroxidase using mouse monoclonal antibodies. The infiltration was graded (marked) to - (none). In 3 cases, tumor-infiltrating lymphocytes were remarkably increased at the delivery of a small dose of irradiation (approx. 10 Gy): 2 of them showed remarkable radiosensitivity, and the lymphocyte subpopulation of the cancer tissue was mainly composed of Leu-3a + 3b-positive and Leu-8-negative lymphocytes (helper inducer T lymphocytes or delayed-type hypersensitivity cells). On the other hand, the third one proved to be rather radioresistant, and the lymphocyte subpopulation was mainly composed of Leu-14-positive lymphocytes (B lymphocytes). These findings indicate that the analysis of the lymphocyte subpopulation infiltrating into cancer tissues at the delivery of small doses of irradiation is applicable as a predictive assay in radiotherapy of squamous cell carcinoma of the oropharynx and hypopharynx.

High-Dose-Rate Intracavitary Irradiation in the Surgical Treatment of Cancer of the Thoracic Esophagus

Thoracic esophageal cancer upon diagnosis is frequently found to be already advanced and also to have metastasized to the lymph nodes even in the early stages. Current surgical treatment operatively excises lymph nodes in three major areas (cervical, thoracic, and abdominal). It is difficult to know whether this operative treatment always contributes to the therapeutic improvement. However, advances in surgery have led to greater understanding about the ease with which esophageal cancer metastasizes to the lymph nodes. Accordingly, extensive dissection is not very effective particularly for advanced cancer. We feel that a new approach is needed to improve therapeutic results for the treatment of advanced esophageal cancer.

Development of new method image diagnosis through hybrid PACS -- with a special concern to a dynamic image

We conceived a hybrid PACS which combines analogue and digital elements where it is required. We experimented a clinical application of the dynamic image utilizing the analogue element which is a feature of the hybrid PACS. With the analogue optical disk, dynamic image acquisition of 30 frames per second is possible and image recording is also possible with any modality of X-ray fluoroscopy function. In addition, X-ray dose to the patient is one-fifth to one-tenth compared with the conventional cine filming method while its still image is clear and a data acquisition to the PACS is easy. We applied this system to the areas of the otorhinolaryngology, orthopaedics and respiratory disease and could perform a various analysis of the disease status under natural conditions, also we found that this system is useful for judging an effect of a treatment as well as jugding a functional recovery after an operation and an effect of a rehabilitation. We are also planning to extend the application to the areas of the digestive system and the group examination from now on.

Magnetic resonance imaging in the diagnosis of tumors at the base of the skull.

The diagnostic efficacy of MRI (magnetic resonance imaging) was compared with that of CT (computed tomography) in 5 patients with tumors at the base of the skull.Tumors in the areas surrounded by bones at the skull base were clearly imaged without the artifacts seen in CT scans.Multiplane imaging can be obtained easily with MRI. Sagittal sections are of great use in visualizing vertical expansion of the tumor. Loss of the black rim of the compact bone at the skull base and loss of the high signal intensity of the fatty bone marrow were comfirmed at surgery to be signs of skull base destruction. The authors stress that MRI is very valuable in planning the treatment of tumors of the skull base.