Naguib A. Samaan

Medullary Carcinoma of the Thyroid: A STUDY OF THE CLINICAL FEATURES AND PROGNOSTIC FACTORS IN 161 PATIENTS

The natural history and prognostic factors of medullary carcinoma of the thyroid (MCT) were studied in 161 patients seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1944 and 1983. One hundred twenty-five patients (77.6%) had the sporadic variety of MCT, 31 patients (19.3%) had multiple endocrine neoplasm (MEN) type IIa and 5 patients (3.1%) had MEN-IIb. The disease occurred equally in both sexes (M:F ratio 1:1.05). Thyroid nodules were the most common presenting feature especially in patients with the sporadic disease and MEN-IIb. Fifteen patients with MEN-IIa had occult MCT; the diagnosis was made through screening of family members with calcitonin measurement before and after stimulation with calcium or pentagastrin. Sixteen patients with MEN-II had pheochromocytoma and 7 had hyperparathyroidism. Total thyroidectomy was the most commonly performed operation. The lowest incidence of recurrence occurred in patients who underwent total thyroidectomy and modified neck dissection. Radioactive 131I was used as adjunct to surgery in 19 patients but it did not improve the survival or lower the incidence of recurrence. Patients who received postoperative radiotherapy had significantly lower adjusted survival rates than those treated by surgery alone, but we tended to irradiate patients with more advanced disease. Chemotherapy was administered to 11 patients with disseminated metastases but the response was poor. The 5- and 10-year adjusted survival rates of all the patients with MCT were 78.2% and 61.4%, respectively. Patients with MEN-IIa had much better rates than patients with sporadic disease (p = 0.0005), who were 7.74 times more likely to die of MCT. The stage of the disease at presentation was a major prognostic factor. Patients with stages III or IV disease were 7.31 times more likely to die of MCT than those with stages I or II. There was no significant difference in survival between patients with stages I and II or III and IV. The presence of cervical lymph node metastases did not affect the survival adversely. Direct extension with involvement of tissue was a bad prognostic sign. Patients younger than 40 years old at the time of diagnosis of MCT had a significantly better adjusted survival rate than those who were older. Women had a better prognosis than men, who were 1.89 times more likely to die of MCT. Diarrhea was a bad prognostic sign. However, it occurred more frequently in patients with advanced stages of the disease and larger tumor mass.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal cortical carcinoma a study of 77 cases

Seventy‐seven patients with histologically proven adrenal cortical carcinoma seen at the University of Texas M. D. Anderson Hospital (1950–1981) were studied. Thirty‐nine were women (mean age at diagnosis, 36.6 years), and 38 were men (mean age at diagnosis, 48.3 years). On presentation, 41 of 74 had abdominal symptoms (55.4%) and 25 of 74 had an abdominal mass (33.8%). Twenty‐six patients (33.8%) were found to have clinically functional disease (18 women, 8 men). At diagnosis, 26 (33.8%) had clinical or radiologic signs of distant metastases. Preoperative radiologic studies yielded an abnormal intravenous pyelogram in 42 of 51 (82%), an abnormal abdominal ultrasound in eight of nine (88.9%), abnormal computerized tomography in 10 of 10 (100%), and abnormal arteriogram in 18 of 19 (94.7%). Surgery for localized or regional disease was associated with a disease‐free interval of at least 2 years in 16 of 34 patients (47%). The use of opDDD, abdominal radiotherapy, and systemic chemotherapy produced demonstrable effects in nine of 47 (19.1%), two of nine (22.2%), and three of 26 (11.5%), respectively. Distant metastases occurred in 60 patients, commonly in lung, liver, peritoneal and pleural surfaces, lymph nodes, and bone. Analysis of survival data showed a 5‐year survival of approximately 30%. The authors concluded that early diagnosis and radical surgery offer the only prospects of long‐term survival and the possibility of cure.

Differential mutagen susceptibility in cultured lymphocytes of normal individuals and cancer patients

When cultured human lymphocytes were treated with a radiomimetic chemical bleomycin, metaphase chromosomes from different individuals exhibited a wide spectrum of responses in terms of number of chromatid lesions. This variability is interpreted as the result of capability for DNA repair. Among 100 healthy, normal individuals tested, nearly 60% showed a mean breaks per cell rate in the range of 0.20-0.60, whereas, only 12% showed breaks per cell rates above 1.00. On the other hand, among 75 cancer patients, 60% showed breaks per cell rates above 1.00. It is believed that differential responses to a mutagen have genetic implications. Individuals with DNA repair deficiencies may be more susceptible to carcinogens and, therefore, are more susceptible to neoplastic induction.

Immunoreactive calcitonin in the mother, neonate, child, and adult

Immunoreactive calcitonin (iCT) was measured in umbilical arterial and venous blood and in maternal peripheral blood in 32 normal deliveries. The results were compared with values found in nonpregnant adult females. The umbilical arterial blood contained significantly higher concentrations of iCT than umbilical venous blood (p less than 0.001). The serum iCT in maternal peripheral blood was significantly higher than in normal nonpregnant subjects (p less than 0.001). Serum iCT was also measured in 342 male and female subjects ranging in age from 1 hour to 60 years. Serum iCT was found to be high early in life and to diminish with age. Our data suggest that calcitonin may be of physiologic significance in bone formation during intrauterine life and childhood. High serum iCT may also be responsible for the hypocalcemia seen in the neonatal period.

Radioactive Iodine in the Treatment of Medullary Carcinoma of the Thyroid

To determine the value of adjunct 131I therapy in medullary carcinoma of the thyroid (MCT), two groups of patients with histologically proved MCT were studied. Group A consisted of 15 patients (6 men and 9 women) treated by surgery, followed by an ablative dose of 131I, and group B included 84 patients (39 men and 45 women) treated by surgery alone. Patients in group A were followed for 1.5-14 yr (median, 53 months), and those in group B were followed for 1-27 hr (median, 75 months). Seven patients (46.6%) from group A and 36 patients (42.9%) from group B developed recurrence or metastasis. The 5- and 10-yr survival rates were 87.5% and 75% for group A and 89% and 74% for group B; the difference was not significant (P greater than 0.05). The changes in serum calcitonin levels in 4 patients of group A were not different from those in patients who did not receive 131I. We conclude that 131I has no value as an adjunct to surgery in the management of MCT.

Diagnosis, localization, and management of pheochromocytoma pitfalls and follow‐up in 41 patients

Forty‐one patients who had pheochromocytoma are described. These patients represent the experience of the authors over the last 19 years. The diagnoses, investigations, treatments, and pitfalls of this study and the management of these patients are described. The most sensitive screening test was the urinary measurement of catecholamines, vanillylmandelic acid (VMA), and metanephrines. The most useful localizing procedure was the metaiodobenzylguanidine (MIBG) scintigraphy and computed tomography (CT). After careful alpha and beta adrenergic blockade in 32 patients, no complications occurred during or after tumor resection. When this procedure was ignored even in patients who had normal blood pressure before surgery, severe cardiovascular complications occurred and two patients died. In familial pheochromocytoma, bilateral adrenalectomy with preservation of normal adrenal cortical tissue when possible may be the method of choice, but careful follow‐up is warranted.

Hypercalcemia in disseminated candidiasis

Abstract Hypercalcemia is described in a patient in whom disseminated candidiasis developed during treatment for acute lymphocytic leukemia. Increased transformation of serum hydroxyvitamin D to 1α,25-dihydroxyvitamin D is proposed as the underlying mechanism for the development of hypercalcemia. The possible mechanisms responsible for hypercalcemia in granulomatous diseases are reviewed.

Effect of L-asparaginase on carbohydrate metabolism

Abstract Glucose tolerance tests and simultaneous serum insulin and human growth hormone (HGH) levels were determined in 4 patients undergoing cancer chemotherapy with L-asparaginase. A significant impairment occurred in the glucose tolerance test in two of these patients receiving L-asparaginase. Serum insulin levels decreased significantly in all patients. An additional patient had a very low serum insulin level despite severe hyperglycemia which preceded his death. In all patients HGH remained normal to low. It appears that the hyperglycemia which results from L-asparaginase therapy is due to a decrease in insulin synthesis.

Suprarenal mass and its differential diagnosis

Nine cases of suprarenal masses without endocrine abnormalities are presented: 2 adrenal pseudocysts, 2 adrenal myelolipomas, 2 neuroblastomas, 1 lymphoma metastatic to the adrenal glands, 1 teratoma, and 1 adrenal cortical carcinoma metastatic to the contralateral gland. The clinical and radiologic findings are discussed. Noninvasive and invasive procedures and their usefulness in diagnosing masses in the suprarenal area are reported. The importance of metastases to the adrenal glands in the differential diagnosis of suprarenal masses was investigated by reviewing the autopsies done from January through June, 1979, at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas. Adrenal metastases were found in 26 per cent of the cases studied. Breast and lung carcinomas and lymphomas were the most commonly found neoplasia. The relative incidence of microscopic and macroscopic metastases in all patients with tumor is discussed.

Immunoperoxidase study of uncommon parathyroid tumors. Report of two cases of nonfunctioning parathyroid carcinoma and one intrathyroid parathyroid tumor-producing amyloid

Nonfunctioning carcinomas of the parathyroid gland are rare and difficult to diagnose. They are often confused with thyroid tumors or with metastasis from other sites. We report two cases of nonfunctioning parathyroid carcinomas; one was originally diagnosed as follicular carcinoma of the thyroid gland. The immuno-histochemical demonstration of parathormone in the tumor cells established the parathyroid origin of these neoplasms. An intrathyroid parathyroid tumor, associated with large amounts of interstitial amyloid, mimicking medullary carcinoma of the thyroid, in a patient with primary hyperparathyroidism is also reported. Positive immunoreaction in the tumor cells for parathormone, negative staining for calcitonin, and the return of patients serum calcium levels to normal after tumor resection, confirmed the parathyroid nature of this neoplasm. Immunohistochemistry studies proved to be extremely helpful in establishing the diagnoses of these unusual parathyroid tumors.