In this study, young patients identified by direct DNA analysis as carriers of a RET mutation characteristic of MEN-2A had no evidence of persistent or recurrent medullary thyroid carcinoma five or more years after total thyroidectomy. A longer period of evaluation will be necessary to confirm that they are cured.
ObjectiveThe purpose of the study is to determine whether reoperation for medullary thyroid carcinoma (MTC), performed with low morbidity in carefully selected patients, consistently results in improvement as determined by lowering of stimulated calcitonin levels.
BackgroundPersistent or recurrent elevation of stimulated plasma calcitonin levels occurs in >50% of patients after primary operation for MTC. Success of reoperation with clearance of metastatic cervical nodal disease has been hampered by failure to identify patients with distant metastases and by inadequate removal of involved nodal groups.
MethodsSince 1992, the authors have evaluated 1 15 patients with recurrent or residual MTC. Fiftythree patients have not undergone operation because of extent of disease, previous extensive treatment, medical condition, or patient choice. Sixty-two patients underwent surgery. Ten patients had laparoscopic or open examination of the liver, the results of which showed liver metastases. Seven patients had palliative debulking of cervical tumor. In 45 patients without evidence of distant metastases, cervical operation was carried out with curative intent. Removal of central, upper mediastinal, and lateral nodes (levels 11, Ill, IV, VI, and VIl) was done.
ResultsSeven of eight patients who had palliative resections are alive without symptoms. In patients who underwent curative resections, postoperative stimulated calcitonin levels were in the normal range in 17 patients (38%) and were not significantly lowered in 6 patients (13%). There were no deaths, and no transfusions were used.
ConclusionsThese results are a significant improvement over the authors' previous series and reflect better preoperative identification of patients with disease confined to the neck and improved operative strategy based on knowledge of the pattern of nodal spread of MTC.
In an evaluation of 213 patients from 15 kindreds with familial medullary thyroid carcinoma (MTC), we detected 41 subjects from two kindreds (L and O) who had MTC but no extra-thyroidal manifestations (hyperparathyroidism, phaeochromocytomas or mucosal neuromas) of multiple endocrine neoplasia (MEN) type IIa or IIb. In screening 178 members of the L and O kindreds, we found no evidence that any of them had died from MTC. To assess whether the malignancy was relatively indolent in these families, 20 selected subjects from the two kindreds were compared with 33 MEN IIa subjects. Both groups had clinically occult disease which was diagnosed biochemically by documenting elevated plasma calcitonin (CT) levels following stimulation with intravenous calcium and pentagastrin. There were no differences in the peak stimulated plasma CT levels at the time of diagnosis (1055 +/- 236 pg/ml versus 1096 +/- 191 pg/ml) or the incidence of regional lymph node metastases (0/20 versus 1/33) in the two groups. The mean age at diagnosis, however, was significantly higher in patients of the L and O kindreds than in patients with MEN IIa (43.1 +/- 3.4 years versus 21.1 +/- 2.2 years; P less than 0.001) indicating that in the two kindreds the MTC either developed at a later age or grew more slowly. This study demonstrates that MTC may occur in a familial pattern distinct from its presentation as MEN IIa or MEN IIb. In this setting it appears to be the least aggressive form of MTC yet described.
Genetic testing identifies patients harboring an MEN1 mutation before the development of clinical signs or symptoms of endocrine disease. When genetically positive patients are carefully studied prospectively, biochemical evidence of neoplasia can be detected an average of 10 years before clinically evident disease, allowing for early surgical intervention. Genetically positive individuals should undergo focused cancer surveillance for early detection of the potentially malignant neuroendocrine tumors that account for most of the disease-related morbidity and mortality.
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