Katsutaro Shimaoka

A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma.

A randomized evaluation of the effectiveness and toxicity of the combination of doxorubicin and cisplatin and of doxorubicin alone in patients with advanced thyroid carcinoma was carried out. Ninety‐two patients were entered and 84 were evaluable. They were stratified according to histological classification, Eastern Cooperative Oncology Group (ECOG) performance status, and metastatic sites. Forty‐one patients received doxorubicin as a single agent and seven had partial response (17%). Forty‐three patients received the combination, and there were five complete and six partial responses (combined response rate of 26%). This difference for overall response rate is not significant (P > 0.1). However, five complete responses were seen in the combination‐treatment group, whereas none were observed in the single‐agent treatment group; a significant difference was obtained (P = 0.03). Four of these five complete responders survived for more than 2 years, and two patients remained in a complete response after the discontinuation of therapy and are still alive. None of the partial responses exceeded 2 years in duration. The life‐threatening toxicities from chemotherapy occurred in five patients treated with the combination of drugs and two treated with doxorubicin alone. However, none of the toxicities were fatal. The study has shown clearly that the quality of response achieved by the combination of drugs is far superior to that achieved by single‐agent chemotherapy.

Chlorambucil vs. combined chlorambucil‐corticosteroid therapy in chronic lymphocytic leukemia

Eleven patients with chronic lymphocytic leukemia were treated with chlorambucil alone and 15 patients received combined chlorambucil‐prednisone therapy in a double‐blind study. Mean age, duration of disease, physical findings, and hematologic data in the two groups were essentially comparable. Complete remission was observed in 3 and partial remission in 10 of the patients in the chlorambucil‐prednisone treated group; but only one of the patients obtained complete and four showed partial remission with chlorambucil alone. This difference was statistically significant (p < 0.05). Hematologic toxicity was less frequent in the combination group. Two‐year survival was 93% for combination group and 54% for chlorambucil‐treated group. The difference, however, was not statistically significant. Our data indicate that chlorambucil‐prednisone therapy is superior to chlorambucil in the treatment of chronic lymphocytic leukemia.

Thyroid abnormalities associated with treatment of malignant lymphoma

The effects on the thyroid of radiation therapy to the neck and/or chemotherapy were investigated in 54 Hodgkins and 72 non‐Hodgkins lymphoma patients. These patients had received radiation therapy with doses ranging from 2000 to 4000 rad (median 3600 rad) to the cervical or mantle fields and/or multiple‐agent chemotherapy following usual staging procedures. Palpable abnormalities of the thyroid were found in 15 patients. The patients with irradiation to the neck had a higher incidence of hypothyroidism than those patients treated with chemotherapy alone (31/74 vs. 8/52, P < 0.001 for TSH and 10/74 vs. 1/52, P < 0.025 for T4). A higher frequency of elevated serum TSH levels and antithyroid antibodies were also observed in patients receiving radiation therapy alone to the neck than in those receiving both radiation therapy and chemotherapy (19/33 vs. 12/41, P < 0.025 for TSH and 16/33 vs. 7/41, P < 0.01 for antibodies), suggesting that chemotherapy agents may reduce the thyroid dysfunction induced by irradiation. There was no difference in prevalence of elevated TSH levels following irradiation to the neck between patients in whom lymphangiogram was or was not performed (21/51 vs. 10/23).

Squamous cell carcinomas and adenosquamous carcinomas originating from the thyroid gland

Three cases of squamous cell carcinoma and 3 cases of mixed squamous and glandular carcinoma were reported. Pathologic differential diagnosis of these rare primary tumors of the thyroid gland were discussed. All except 1 case occurred in elderly patients; their clinical behavior was more aggressive than that of differentiated papillary or follicular carcinoma of the thyroid gland and more like that of undifferentiated carcinoma. It is suggested that the tumor be treated more vigorously at its initial stage.

Appraisal of aspiration cytology in management of Hodgkin's disease

The value of aspiration cytology in the management of Hodgkins disease is shown in this study of 228 paients and 403 aspirations; 385 from lymph nodes and 18 from extranodal masses. In all patients the initial diagnosis was established on surgical biopsy. Aspirates were helpful in staging, defining extension of unusual radiation fields, and in recognizing residual disease and relapses after therapy. Adequate material was obtained in 80% of aspirations. The diagnosis of Hodgkins disease could not be established in the adequate cytologic sample in 9.9% of cases. In 5.5%, the diagnosis was that of benign reactive hyperplasia and in 4.4%, non‐Hodgkins lymphoma. Unsatisfactory material was usually obtained from nodes less than 1 cm in diameter or from residual lesions following radiation or chemotherapy. Only 14 of 93 such lesions proved to have active disease during follow up. There were no significant complications. Characteristics of the varied aspects of aspirated tumor cells found in Hodgkins disease are described.

Suppressive therapy of nontoxic goiter

Abstract In a double-blind study, 114 patients with clinically benign nontoxic goiter were treated either with liothyronine (T3), 50 μg/day, or thyroxine (T4), 200 μg/day. After 12 weeks of therapy, patients whose goiters decreased in size were continued on the same therapy for an additional 16 weeks. Those who did not respond were randomly divided into two groups: in one group the same dose of the same medication was continued, and in the other twice the dose of their original medication was given. By the end of 28 weeks, 40 of 54 patients treated with T3 and 29 of 59 patients treated with T4 showed a significant decrease in goiter size. The difference in effectiveness of the two agents was statistically significant (p T3 produced a uniform and consistent depression of radioiodine uptake and circulating hormonal iodine levels, and was effective shrinking both small and large thyroid nodules, whether or not radioiodine uptake was reduced to hypothyroid levels. T4 uniformly increased circulating hormonal iodine levels. However, in T4-treated patients who responded with regression of thyroid nodules, suppression of radioiodine uptake was substantially greater than in those who did not respond.

Anaplastic carcinoma of the thyroid following external irradiation

Two patients with anaplastic carcinoma of the thyroid following irradiation for Hodgkins disease are presented, and the previously reported cases briefly reviewed. The risk of late development of thyroid carcinoma is life‐long and high‐dose irradiation in patients with prolonged life expectancy may result in anaplastic carcinoma as well as less malignant histological forms.

Plasma cell neoplasm involving the thyroid.

Involvement of the thyroid gland by plasma cell neoplasms is very rare. On review of 248 cases, we found 4 cases in which pathological evidence of plasms cell neoplasm in the thyroid was verified. This was a heterogeneous group of patients; the thyroid involvement was clinically recognized as a site of extramedullary plasma cell neoplasm in one patient and as a part of generalized disease in two patients. In another patient with generalized disease, the thyroid involvement was discovered at autopsy.

Carcinoma of thyroid associated with other primary malignant tumors

This paper deals with patients who have both a primary thyroid cancer and a primary malignant tumor of another organ. Fourteen such cases were in the authors material and 165 cases reported by others are reviewed. The pattern of the tumors associated with thyroid cancer corresponds to the reported frequency of neoplasms of various sites, with the exception that there is an excessive number of cases of leukemia. These may be related to radio‐iodine therapy for the thyroid cancer. If a patient has a cancer and then develops a malignant nodule in the thyroid, this is much more likely to represent a metastasis than a second primary neoplasm; however, it is exceedingly difficult, if not impossible, to differentiate between the 2 on clinical grounds. Usually, metastatic cancer to the thyroid gland is a late manifestation of tumor dissemination but occasionally it may appear early. In such cases, it may be necessary to explore the neck to determine whether the lesion is a second primary or a metastasis.

Adenosquamous carcinoma of the thyroid after radiotherapy for Hodgkin's disease. A case report and review.

This is a case report of a patient who had received radiation therapy for Hodgkins disease and 48 years later developed adenosquamous carcinoma of the thyroid gland. Radiation associated thyroid carcinoma is usually of differentiated variety and carried no different prognosis than one not related to radiation. Coexisting adenocarcinoma and squamous cell carcinoma is a very rare event, but makes the prognosis of patients with thyroid carcinoma much poorer. As a result, this kind of patient requires early recognition and aggressive therapy.