Surgery of differentiated cancer of the thyroid

A retrospective study on patients with differentiated thyroid carcinoma operated on at the 3rd Department of General Surgery of the University "La Sapienza" of Rome from 1970 to 1996 was performed. In 709 patients total thyroidectomy was performed as the minimal procedure acceptable, while 19 patients had subtotal thyroidectomy out of necessity. A functional ipsilateral or bilateral lymphnectomy of the neck was performed in 256 cases. This wider operation is indicated in the presence of metastatic lymph nodes and on principle in patients older than forty-five years in which at least another risk factor is present. Long term follow-up (12 years) was assured in 302 patients and the survival rate was 92% independently from the histotype (papillary or follicular). The survival rate of a group of 120 patients (80 with papillary and 40 with follicular carcinoma) was analyzed in relation to the risk factors. This group analysis demonstrated a very low mortality rate in patients with low risk index and an increased rate in patients with a high risk index.     

Immunoradiometric assay of thyroglobulin in patients with differentiated thyroid carcinomas: need for thyroglobulin recovery tests

As interference from thyroglobulin autoantibodies appears to have been overcome in new commercial thyroglobulin assays by the use of monoclonal antibodies, the need for thyroglobulin recovery tests became uncertain. Sera (n=45) from patients with differentiated thyroid carcinomas were selected on the basis of a thyroglobulin recovery value below 70% in the Dynotest Tg immunoradiometric assay (Brahms) routinely used in our laboratory. Serum thyroglobulin levels were then measured using three other commercial immunoradiometric assays: thyroglobulin ERIA (Pasteur), HTGK (Sorin) and ELSA HTG (Cis Bio International). Thyroglobulin autoantibodies were measured using the Thyrak assay (Brahms). Although many patients were thyroglobulin antibodies-negative (< 200 U/ml, n=26), most immunoradiometric assays failed to detect thyroglobulin in patients with evidence of recurrence. Low thyroglobulin values associated with low thyroglobulin recovery in thyroglobulin antibody-negative patients appear to be more biologically relevant than a single low thyroglobulin value, which can lead to lack of medical intervention. We conclude that the thyroglobulin recovery test is a prerequisite for the correct interpretation of serum thyroglobulin levels determined with immunoradiometric assays in the follow-up of thyroglobulin autoantibody-negative patients treated for differentiated thyroid carcinomas.     

Guidelines for the use of radio-iodine, thyroid hormone, and treatment of metastatic disease in patients with differentiated thyroid cancer

The treatment of metastatic differentiated thyroid carcinoma is currently at a crossroad. The stunning effect of imaging doses of RAI on subsequent treatment doses is being recognized. Alternatives to RAI imaging for diagnostic purposes are being tested; these include ultrasonography for local and cervical nodal remnants/recurrences, Sestamibi and other isotope scanning that do not require the discontinuation of TSH suppression, and the measurement of circulating thyroglobulin that is rapidly becoming the cornerstone of the detection and the treatment follow-up of metastatic carcinoma.     

Radio-guided surgery for lymph node recurrences of differentiated thyroid cancer

The objectives of this study were to assess the reliability of radio-iodine (131I) and a gamma probe for radio-guided surgery (RGS) to detect and then radically dissect lymph node recurrences (LNRs) in 10 patients with differentiated thyroid cancer (DTC). The major inclusion criterion was the presence of an iodine-positive LNR after previous total thyroidectomy and at least two ineffective 131I treatments. The protocol was designed as follows. Day 0: all patients were hospitalized and received 3.7 GBq of 131I in the hypothyroid condition. Day 3: presurgery whole-body scan with a therapeutic dose (TxWBS). Day 5: neck surgery using a gamma probe (Navigator GPS, AutoSuture, Italy), recording the absolute counts and the lesion/background (L/B) counts ratio. Day 7: post-surgery TxWBS performed using the remaining radioactivity. The presurgery TxWBS was positive in all patients, and the post-surgery TxWBS showed a negative pattern in 7 of 10 patients, suggesting the efficacy of the surgical procedure in most of the patients. After RGS the mean decrease in the absolute counts and the L/B counts ratio were 77.6% (52.7% minimum, 94.6% maximum) and 77.4% (52.3% minimum, 94.8% maximum), respectively. After operation the surgeon judged the procedure to be decisive in two patients, favorable in six, and irrelevant in two. The final histologic examination showed the presence of 78 lymph node metastases (mean of 8 per patient). There were 33 neoplastic lesions found by both TxWBS and gamma probe evaluations; 41 were shown only by gamma probe, and 4 were negative by both TxWBS and gamma probe evaluations. This protocol permitted us to look for neoplastic foci with high sensitivity and specificity, and we were able to remove lymph node metastases resistant to radioiodine therapy at a single session. The protocol also allowed detection of some additional tumoral foci in sclerotic areas or behind vascular structures that are difficult to identify and were not seen at the presurgery TxWBS evaluation. However, because of the possible false-negative results, complete excision must be undertaken in high risk patients with a local recurrence to eradicate the largest number of lymph nodes, independent of the counts measured by the gamma probe.     

Low-risk diet for breast cancer in Italy

To define a low-risk diet for breast cancer in Italy, a multicentric case-control study of 2569 incident cases of breast cancer and 2588 controls from Italy was analyzed. A logistic regression model was applied to the estimated intake of five macronutrients and used to compute a diet-related risk score (RS). The pattern of macronutrient and food group intake across RS deciles was defined. The mean of diet-related RSs across subsequent risk deciles ranged from 0.83 to 1.44. Total energy intake first decreased slightly, from the first to the second decile, and then increased, mostly in the last three risk deciles. Intake of starch increased in absolute and relative terms, whereas saturated fat intake rose in absolute terms but remained stable as a proportion. A relative decline was observed for unsaturated fat and sugars, with a hint, however, of U-shape effect. From a food group viewpoint, there was a marked increase in the intake of bread and cereal dishes, cakes and desserts, and refined sugar across subsequent deciles, whereas the consumption of vegetables, olive and seed oils, and fruit decreased.     

Outcome of differentiated thyroid cancer in Graves' patients

The clinical behavior and outcome was evaluated in 21 nonoccult differentiated thyroid carcinomas occurring in Graves' patients during the period 1982-94 and compared with that of matched tumors occurring in euthyroid controls (n = 70). At surgery, patients with Graves' disease showed distant metastases more frequently than euthyroid patients (3/21 = 14.3% vs. 1/70 = 1.4%, P = 0.0556). Graves' patients also showed a significantly higher cumulative risk of recurrent/progressive distant metastases or total adverse events (odd ratios = 3.14 and 2.07, respectively) as compared with euthyroid patients. At the last follow-up visit, persistence of distant metastases was also more frequent in the Graves' group (P = 0.007), although the cumulative individual dose of radioiodine administered was higher than in the control group (median dose = 805 mCi vs. 350 mCi). Two patients died in the Graves' group vs. none in the control group. Circulating thyroid stimulating antibodies were present in all patients but one and persisted as long as signs of disease were evident. These findings indicate that differentiated thyroid carcinomas in patients with Graves' disease are more aggressive than those occurring in matched euthyroid controls and should, therefore, be managed accordingly.     

Importance of scintigraphy in the evaluation of surgical treatment outcome in differentiated cancer of the thyroid gland

Experience of radionuclide investigation in 493 patients with differentiated cancer of thyroid gland is summarized. The consequences due to incorrect conducting of patients with cancer after the operation were adduced on distinct examples. The program for conducting and observation of patients with thyroid gland cancer after the operation conduction was proposed directed on the early diagnosis of recurrencies and metastases, determination of indications for radioiodine therapy.     

Outcome of differentiated thyroid cancer diagnosed in pregnant women

The clinical features and outcome of thyroid cancer in 61 pregnant women (mean age, 26.0 +/- 5.9 SD yr) and in 528 female, age-matched controls who were not pregnant (mean age, 26.3 +/- 5.9 SD yr) were compared. Median follow-up was 22.4 and 19.5 yr [P = not significant (NS)] in the two groups, respectively. The thyroid nodule was asymptomatic and discovered on routine examination more often in the pregnant women (74%) than in controls (43%, P < 0.001); other clinical and tumor features were similar in the two groups. Most of the pregnant women underwent thyroidectomy after delivery (77%) or during the second trimester of pregnancy (20%). Near-total thyroidectomy was done in 43 (73%) of the pregnant women and 265 (59%) of the controls (P = NS), and nearly the same proportion of both groups (30% and 25%, respectively) were treated with 131I postoperatively. Outcome in the pregnant women and controls, respectively, was: cancer recurrence 9 (15%) and 107 (23%, P = NS); distant recurrences 1 (2%) and 12 (3%, P = NS), and cancer deaths 0 and 6 (1.2%, P = NS). Outcomes were similar when surgery was done during or after pregnancy, despite a longer delay in treatment of the latter (1.1 +/- 1.0 vs. 16.1 +/- 19.7 months, P < 0.001). This study suggests that the prognosis of differentiated thyroid cancer is the same in pregnant women and nonpregnant women of the same age, and that the diagnosis and treatment of thyroid cancer occurring during pregnancy can be delayed until after delivery in most patients.     

Outcome of pregnancy after radioactive iodine treatment for well differentiated thyroid carcinomas

This study sought to determine the outcome of pregnancy in female patients with differentiated thyroid carcinoma who became pregnant after radioactive iodide treatment. A total of 779 female thyroid cancer patients were treated at Chang Gung Medical Center in Linkou between January 1977 and December 1995. The medical records of these patients were reviewed retrospectively. Thirty-seven of these patients had well differentiated thyroid carcinoma receiving 131I treatment and conceived at a mean age of 27.97 +/- 3.49 year-old. A total of 58 pregnancy episodes were recorded during this study period. Among these 37 patients, 3 episodes of artificial abortion, 8 episodes of spontaneous abortion and 2 threatened abortions were observed. These patients delivered a total of 47 babies including 3 premature babies. Seven of these patients conceived within 6 months after the last administration of 131I, including 2 cases within 1 month, 4 cases within 4 months, and 1 patient within 5 months. Of these 7 patients, only one patient who conceived within 6 months after the last administration of 131I (14.3%) had a spontaneous abortion. The present results suggest that previous administration of 131I in female patients with well differentiated thyroid cancer does not result in demonstrable adverse effects in subsequent pregnancies. However, further studies involving long-term follow-up of children delivered by mothers who became pregnant within 6 months after the last administration of 131I is needed to further elucidate the possible chronic effects and sequelae of 131I therapy on subsequent pregnancies.     

Chest X ray: routine indication in the follow-up of differentiated thyroid cancer?

Models of the bacterial ribosome based on recent structural analyses are beginning to provide new insights into the protein synthetic machinery. Central to evolving models are the high-resolution structures of individual ribosomal proteins, which represent detailed probes of their local RNA and protein environments. Ribosomal proteins are extremely ancient molecules; the structures therefore also provide a unique window into early protein evolution. Many of the proteins contain domains that are present in more recently evolved families of RNA- and DNA-binding proteins. Such structural homology can be used to predict mechanisms by which proteins interact with RNA in the ribosome.     

The changing role of radioiodine in the management of differentiated thyroid cancer

Craniosynostosis occurs in one out of 2,000 births. It results in primary skull deformations requiring surgical repair, in infants with a body weight of less than 10 kg. Pure craniosynostosis is the most frequent situation, where the risk for cerebral compression during brain development is the lowest. Therefore the aim of surgical correction in this case is mainly cosmetic. Conversely, in syndromic craniosynostosis, associated malformations are more common and cerebral, visual and respiratory consequences of complex facio-craniosynostosis are usually severe. Current surgical techniques consist of a total skull vault reconstruction which carry a high risk of sudden and major blood losses. Intraoperatively, whatever the type of craniosynostosis, mean blood losses corresponding to 90% of estimated red cell mass have to be anticipated. These blood losses vary according to the type of skull deformation and the type of surgery. Accurate evaluation is usually difficult and must be based more on calculation of red cell mass variations than on simple monitoring of surgical drainage. Invasive haemodynamic monitoring is always required. To reduce the amount of homologous blood transfusion, peroperative haemodilution seems to be the most suitable technique, due to unresolved technical difficulties in autotransfusion practice in infants. Severe facial deformities are associated with chronic hypoxaemia and cerebral compression representing major risk for these children in poor condition undergoing such major surgical procedures. With experienced teams, this high-risk surgery carries a low peroperative mortality (less than 1%) and morbidity rate. The latter includes essentially transient peroperative hypotension. The excellent final cosmetic and functional results justify the practice of this surgery in children with a bodyweight of less than 10 kg.     

Acute leukemias after treatment with radioiodine for thyroid cancer

Leukemia is an uncommon complication of exposure to radioiodine (131I), used in treatment of thyroid cancer, because low doses are now used. We report two cases of acute myelogenous leukemia developed after the treatment of a thyroid carcinoma with a small dose of 131I.     

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.     

High-resolution ultrasound associated with aspiration biopsy in the follow-up of patients with differentiated thyroid cancer

A previous study showed that recombinant leptin markedly affects the body fat content and thermoregulatory energy expenditure of lean (+/+ and +/fa) suckling-age rats, and we wanted to find out whether leptin in doses that halved body fat of cold-reared lean pups had any effect in thermoneutrally reared lean pups. When +/+ pups were artificially reared from 4 to 16 days of age at thermoneutrality and treated as before with leptin from day 7, their total metabolic rate throughout the treatment period was only 4% higher than that of the control littermates and their final body fat content only 4% lower (both P>0.05). We conclude from comparisons of the results in +/+ pups at cold and thermoneutral conditions that leptin does not stimulate, but rather disinhibits, sympathetically mediated thermoregulatory thermogenesis.     

Cervical lymphadenopathy revealing differentiated thyroid cancer. Review of the literature and therapeutic approach]

Well-differentiated thyroid cancer (i.e. papillary microcarcinoma) may be revealed by a clinically palpable cervical node, especially in young patients. Primary tumor specificity (small-sized, superior location, invasion, multifocality) and characteristics of cervical node involvement (with synchronous central and lateral multiple node spread) require appropriate treatment by a skilled surgeon. Contrary to the primary tumor treatment (total thyroidectomy), surgical management of the cervical node basins remains controversial. Only a special knowledge of the specificity of this disease and cervical lymphatic anatomy will ensure a good prognosis for the patient.     

The non-surgical treatment of thyroid cancer

The non-surgical treatment of thyroid cancer is outlined. The success of chemotherapy and of radiotherapy is dependent on the number of tumour cells present, and immediate postoperative treatment is therefore often valuable. The role of X-ray therapy, radio-iodine, hormones and chemotherapy is discussed for the different histological types.     

ARIMIDEX: a potent and selective aromatase inhibitor for the treatment of advanced breast cancer

Aromatase inhibitors have been available for a number of years and their ability to reduce circulating estradiol levels has been shown to produce clinical benefit in women with advanced breast cancer. Until recently, the only commercially available aromatase inhibitor was aminoglutethimide. Although aminoglutethimide has been shown to be efficacious in the treatment of advanced breast cancer, it does cause significant toxicity and requires the use of concomitant hydrocortisone therapy. Anastrozole is one of a new class of potent aromatase inhibitors able to suppress estradiol to the limit of detection of sensitive assays without suppressing adrenal steroidal synthesis. Two large clinical trials (n = 764) conducted in the U.S.A. and in Europe evaluated two doses of anastrozole, 1 and 10 mg a day, compared to megesterol acetate, 40 mg four times a day, in postmenopausal women who had progressed while on tamoxifen. Response rates and time to progression with anastrozole were similar to those of megesterol acetate. Objective responses (CR + PR) were 10.3%, 8.9% and 7.9% in the 1 and 10 mg of anastrozole and megesterol acetate treatment groups, respectively. Another 25.2%, 22.6% and 26.1% had stable disease for over 24 weeks on 1, 10 mg anastrozole and megesterol acetate, respectively. Anastrozole and megesterol acetate were well tolerated; however, more patients had significant weight gain on megesterol acetate than with anastrozole treatment. The weight gain seen with megesterol acetate continued to increase over time. Anastrozole has a better therapeutic index (fewer side-effects) and has recently been approved by the FDA and a number of other regulatory agencies around the world for the treatment of advanced breast cancer.