Bernard M. Goslings

Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients

Mitotane is considered to be the drug of choice for patients with inoperable, recurrent and metastatic adrenocortical carcinoma, although a favourable effect of this drug on survival has never been documented. We evaluated the efficacy of mitotane treatment of 96 patients with adrenocortical carcinoma followed up in our department between 1959 and 1992. Complete tumour resection was the goal of the initial treatment. Mitotane treatment was classified according to serum trough concentrations on maintenance therapy: low (< 14 mg l-1) or high (> or = 14 mg l-1). Total tumour resection was feasible in 47 patients (49%), and subtotal resection was performed in 37 patients (39%). Patients who underwent total tumour resection survived significantly longer than those who did not (P < 0.001). Adjuvant mitotane therapy (n = 11) did not influence survival after total resection. Sixty-two patients were given mitotane treatment at some time during their illness, only 30 of whom reached high maintenance serum levels. Mitotane treatment with high serum levels had an independently favourable influence on patient survival, using univariate (P < 0.01) and multivariate analysis (P = 0.01). Mitotane treatment resulting in low serum levels was tantamount to not giving mitotane at all. We conclude that mitotane treatment in adrenocortical carcinoma is effective only when high serum levels can be achieved.

Multivariate analysis of survival in differentiated thyroid cancer: the prognostic significance of the age factor

A retrospective analysis of tumour and patient characteristics was performed in 202 patients with papillary (n = 132) or follicular (n = 70) thyroid carcinoma, in order to identify prognostic factors related to survival. The following facts were found to be unfavourably related to survival: follicular histology, extrathyroidal growth of the primary tumour (stage pT4), regional lymph node involvement (stages pN1-3), presence of distant metastases at diagnosis (stage pM1), male sex (in papillary cancer) and old age (only death due to thyroid tumour was evaluated). For 190 patients sufficient material was available to permit extensive histopathological investigation. In patients with papillary cancer the presence of small anaplastic foci and/or greater than 25% solid structures (n = 18) was correlated with a reduced survival rate. Our study underlines the importance of distinguishing, histologically, between papillary and follicular cancer and in addition demonstrates the prognostic value of histological grade in papillary (but not follicular) carcinoma. We applied Coxs proportional hazard model to the survival data of these 190 patients and, after stage grouping, found that tumour stage (locoregional vs. advanced disease) was the most important prognostic factor. The second most important factor was the histological (sub)type (well differentiated papillary carcinoma vs. moderately differentiated papillary carcinoma and follicular carcinoma). Age at diagnosis and sex appeared to be of lesser importance. Therefore our study does not recommend the use of age as a guide for therapeutical decisions in differentiated thyroid cancer.

Role of fine-needle aspiration biopsy and frozen section examination in determining the extent of thyroidectomy.

Abstract. Traditionally the extent of thyroidectomy in patients with nodular thyroid disease has been based on peroperative frozen section examination (FS). Fine-needle aspiration biopsy (FNAB) and FS were evaluated with regard to the reliability to determine whether an operation for cancer is necessary. Both methods were performed in 240 patients operated for nodular thyroid disease and compared with the final histology on paraffin sections. Altogether 72 (30%) patients were found to have a malignant lesion on final histology. Only a malignant FNAB diagnosis and a malignant FS diagnosis were considered positive results for determining the extent of thyroidectomy. The test characteristics were equal: the sensitivity of FNAB and FS was 67%, the specificity 99%, and the accuracy 89%. The positive predictive value was 96% for FNAB and 98% for FS; the negative predictive values were 88% and 87%, respectively. Further analysis of the results indicates that FS is not necessary for patients with a malignant FNAB result. These patients should undergo a therapeutic operation for malignancy. When the FNAB result is uncertain, patients should undergo diagnostic surgery, and definitive surgery should be based on the final histology. Routine use of FS can be omitted.

Prognosis and morbidity after total thyroidectomy for papillary, follicular and medullary thyroid cancer

The prognosis and the morbidity results after total thyroidectomy are reported for 148 patients with differentiated thyroid cancer. Ninety-two patients (62%) had papillary cancer, 27 (18%) had follicular cancer and 29 (20%) had medullary cancer. In the latter group, 16 patients had no clinical signs of a tumour and underwent total thyroidectomy after elevated calcitonin levels were found in a family screening programme. The mean follow-up period was 9.7 years in the present series. The 5- and 10-year overall survival in the patient group with papillary cancer was 97% and 95% respectively, in the group with follicular cancer it was 78% and 50% respectively and in the group with medullary cancer it was 91% and 82% respectively. Significantly associated with reduced disease-free survival were: extrathyroidal growth (P less than 0.0001), distant metastases at diagnosis (P less than 0.0001), follicular histology (P less than 0.0001), age over 40 (P less than 0.001) and male sex (P less than 0.05). In patients with papillary cancer, recurrences were in most cases located in the neck, while recurrences at distant sites were encountered more frequently in patients with follicular or medullary cancer. Accidental permanent unilateral recurrent laryngeal nerve palsy were registered in 1.4% of the nerves at risk; all on the side of the tumour. Permanent hypoparathyroidism was present in 4% of the patients.

Radiation-induced head and neck tumours: Is the skin as sensitive as the thyroid gland?

Six hundred and five persons, randomly selected from a cohort of 2400 patients who had been irradiated 16-46 yr previously for benign diseases in the head and neck region, were traced, recalled and examined for radiation-associated tumours. Three hundred and sixty-seven patients were alive, 179 had died and 66 had emigrated. Two hundred and fifty-seven patients were clinically examined, 87 refused or were not able to participate and 16 could not be contacted. Eighteen of the clinically examined patients had been or were being treated for 20 skin carcinomas with a mean latency of 37 yr. In this group only 7 carcinomas of the thyroid gland were observed, with a mean latency of 38 yr. Eleven carcinomas of the skin and 3 of the thyroid gland were reported in the group which was examined by means of questionnaires. The observed number of carcinomas of the skin is higher than expected according to the dose-effect relationship of UNSCEAR, whereas the number of carcinomas of the thyroid gland is lower. It is concluded that there might be less difference in susceptibility for the induction of tumours by ionizing radiation between the skin and the thyroid gland than is commonly assumed.

Hyperthyroidism following Mantlefield Irradiation for Hodgkin’s Disease

Hyperthyroidism is described in a 20-year-old man treated 8 months before by radiotherapy (mantlefield irradiation) for Hodgkin’s disease. In contrast to hypothyroid dysfunction, hyperfunction of the

Thyroid scintigraphy for the detection of radiation-induced thyroid cancer.

Thyroid scintigraphy with Tc-99m pertechnetate was performed in 249 patients who received radiation therapy for abnormalities in the head or neck in order to determine the role of this examination in the detection of abnormal nodules arising from cancer. These patients received a mean total dose of about 10.1 Gy. The mean follow-up period was 39 years. All patients underwent physical examination without prior knowledge of the scintigram. Scintigrams were evaluated without prior knowledge of the physical examination. In 158 cases, both the physical examination and scintigraphy were negative. In 64 cases, both examinations were positive. In ten patients, the physical examination was positive and scintigraphy was negative and vice versa in 17 patients. Of 249 patients, 28 ultimately underwent thyroid surgery; a total of four had carcinoma. A costbenefit relationship as to routine scintigraphy as a screening procedure is presented. If patients are first screened by palpation, a number of abnormal nodules will be missed. In addition, a considerable number with positive palpation would probably undergo surgery unnecessarily. From a clinical and financial point of view, it is believed that scintigraphy is the examination of choice for screening for radiation-induced thyroid malignancies.