A multivariate analysis of the prognostic factors was carried out on a series of 546 differentiated thyroid cancers followed for 8 to 40 years. For survival, the highest risk factor was associated with age; tumors diagnosed in patients younger than 45 years had higher relapse‐free survival (RFS) and total survival (TS) rates and a slower growth rate. In children, although the RFS and TS at 15 years were high, they decreased later. The second independent prognostic factor was histology. There was no difference between papillary and follicular well‐differentiated (FWD) tumors, but follicular moderately differentiated (FMD) had lower TS and RFS. Among FMD cancers, relapses occurred earlier and the interval between relapse and death was shorter. The third factor was sex. Tumors tended to disseminate more in male than in female patients. The survival rate after relapse was the same, however, suggesting that the growth rates are not different. The presence of palpable lymph nodes also had a significant independent impact on both TS and RFS. Patients treated after 1960 have a better outcome than patients treated earlier, although they did not differ in age distribution, histologic characteristics, sex ratio, or incidence of palpable lymph nodes. The distribution of time intervals between treatment and relapse was not compatible with an exponential failure time model but fit with a log‐logistic model. Relapses can occur as late as 30 years or more after initial treatment. Elevated levels of circulating thyroglobulin have been observed in about 12% of the patients who had been in complete remission for longer than 20 years.

Twenty patients, 16 males and 4 females, aged 11-76 yr, were treated for a metastatic pheochromocytoma at our institution between 1985 and 1990. A neurofibromatosis was associated in 4. Thirteen patients had a unilateral adrenal tumor, 3 had an extraadrenal retroperitoneal tumor, 2 had a bilateral adrenal pheochromocytoma, one had a unilateral tumor with a contralateral medullary hyperplasia and one an adrenal and an extraadrenal pheochromocytoma. Metastases occurred in all patients, at presentation in 11, 10 to 30 months later in 7, and 9 and 28 yr later, respectively in two. Histology did not afford conclusive evidence for malignancy. Catecholamine hyperproduction was present in all, predominantly affecting norepinephrine. Neuron Specific Enolase level was elevated in 11, Neuro-Peptide Y level in 9 and procalcitonin level in 11/18. High dopamine, methoxytyramine and homovanillic acid excretion levels seemed to correlate with large tumors or terminal stage. MIBG uptake was found in 16 after a diagnostic dose and in 1 only after a therapeutic dose. Surgery was performed on primary tumor in 18 and on distant metastase in 10. Iodine-131 MIBG therapy was performed in 11, among whom 9 were evaluable. Cumulative activity ranged from 100 to 711 mCi, in 1 to 6 courses. Symptomatic improvement occurred in 5 patients, stabilization was observed in 3 and tumor partial response in two, which lasted for 28 and 9 months, respectively terminating in a rapidly progressing disease with bone marrow involvement. Moderate myelosuppression occurred in 4 patients. Chemotherapy gave no response in 7 evaluable patients. Fourteen patients died with a median survival of 16 months from diagnosis of metastases (range 3-60). Response to therapy was poor and warrants further cooperative trials.

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.

Forty-nine patients with metastatic nonanaplastic thyroid carcinoma were treated over a 10-year period. Five successive chemotherapeutic protocols were used: a combination of doxorubicin, etoposide, 5-fluorouracil and cyclophosphamide; elliptinium acetate; doxorubicin; cisplatin; and the combination of doxorubicin and cisplatin. Results obtained with the different protocols were very disappointing, with only two objective responses (3%). Phase II trials with new chemotherapeutic agents are warranted in selected cases of nonanaplastic metastatic thyroid carcinoma.

Summary Selective venous sampling catheterisation was performed in 19 patients with medullary thyroid carcinoma without known distant metastases for persistent hypercalcitoninaemia after surgery. Calcitonin (CT) gradients were found in the neck and/or the mediastinum in 18 patients and in five patients at distant sites also. After venous catheterisation, 13 patients were subjected to repeat surgery. Neck and/or mediastinal tumour foci were found in 12 patients at the sites of the CT gradients. Of Medullary thyroid carcinoma (MTC) spreads early to regional lymph nodes in the neck and mediastinum and to distant sites in the liver, lungs and bones (Grauer et al., 1990).The aim of initial surgery is to remove all neoplastic foci. It consists of a total thyroidectomy with bilateral lymph node dissection in the neck and the upper mediastinum (Wahl & Roher, 1988). The normalisation of the serum calcitonin (CT) level after surgery is a strong indicator that neoplastic tissue has been totally removed. However, this is achieved in only 20% of patients with clinical disease (Parmentier et al., 1985). In others, persistently elevated CT levels indicate the presence of residual disease. If localised, this may warrant further surgery. However, a complete work-up, including ultrasonography, computerised tomography or magnetic resonance imaging and bone scintigraphy, frequently yields no positive evidence of localised tumours in these patients with elevated CT levels. Furthermore, owing to previous surgical procedures, the significance of any abnormality may be ambiguous. Scintigraphic procedures have not proved to be sensitive enough to be useful as a routine.Selective venous sampling catheterisation appeared to be a sensitive and specific tool for localising the origin of serum CT in patients with elevated CT levels and no other evidence of disease (Ben Mrad et al., 1989;Gautvik et al., 1989; Frank-Raue et al., 1992). However, given the slow growth rate of most MTCs, the follow-up was too short in these series to elucidate the significance of extracervical gradients and to conclude that this technique could be useful, in terms of relapse and survival rates.The present study is based on 19 patients, with a mean follow-up of 5.5 years after selective venous catheterisation. Eight of these patients have previously been reported (Ben Mrad et al., 1989).Before selective venous catheterisation, all patients were subjected to a clinical examination, including chest radiography, ultrasonography of the neck and liver, computerised tomography of the neck, chest and abdomen and bone scintigraphy. This work-up only permitted the discovery of involved cervical or mediastinal lymph nodes in six patients (nos. 1, 4, 6, 13, 18 and 19).The selective venous sampling catheterisation procedure has already been reported (Ben Mrad et al., 1989). It was performed by the femoral route using a Cook SF 2-cm-long catheter with a 1200 angle and one side-hole tip (Cook, SARL, Paris, France). A standard procedure was used: a mean of 25 samples was obt...

No abstract

A new commercially available kit for thyroglobulin (Tg) measurement [immunoradiometric assay (IRMA) system based on monoclonal antibodies] was used in 479 patients with thyroid carcinoma. The effective working range was 1 ng/ml, and results were strongly correlated with our homemade radioimmunoassay (RIA). This IRMA method is less susceptible to interferences of auto-antibodies than our RIA. During thyroxine (T4) treatment, the Tg level was undetectable in 98% of patients after total thyroid ablation, in 91% after total thyroidectomy and in 42% after lobectomy only. In this situation, Tg was found in all patients with large metastases and in 88% of those with small metastases. Following T4 withdrawal, Tg was detectable in all patients with neoplastic disease and in 13% of those in complete remission after total thyroid ablation. In conclusion, Tg measured with this IRMA method appears to be a reliable marker of differentiated thyroid carcinoma.

mRNAs were isolated from 2 patients suffering from a familial form of a rare variant of medullary carcinoma of the thyroid (MTC), called mixed follicular and medullary carcinoma. The presence of calcitonin (CT) and thyroglobulin (Tg) mRNAs was checked by northern and in situ hybridization and compared with immunohistochemical results. In each case, mRNAs hybridizing to probes specific for CT and Tg were detected. Both proteins were quantified by radioimmunoassay determination in tissue extracts. Patient 1 had 20 ng Tg and 68 ng CT per micrograms total protein, and patient 2 had 0.4 ng Tg and 1.7 ng CT per micrograms total protein. Northern analysis showed that mixed carcinoma expressed several species of both CT mRNAs and Tg mRNAs. The main Tg transcripts present in neoplastic cells (8.5 and 4.8 kb for patient 1 and patient 2) were identical to or smaller than those of normal thyroid tissue (8.5 kb). The tumor CT mRNA (1 kb) was identical to that of normal tissue. In situ hybridization confirmed the presence of CT and Tg mRNA in the great majority of tumor cells. Furthermore, the presence of small amounts of organified iodine was evidenced by analytical ion microscopy in 35% of these cells. This raises an important question regarding the histogenesis of this tumor.