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[Differentiated thyroid cancers. Thyroid recurrence after limited surgery].

Twenty-eight patients with differentiated thyroid cancer presented with local relapse 6 months to 24 years (mean: 7 years) after limited surgery. The tumour was clinically undetectable in 7 cases. Among 22 patients reoperated upon, one died post-operatively, 17.8% had permanent recurrent nerve paralysis and 14.3%, permanent hypoparathyroidism. Metastases were discovered in 15 patients (53.8%), 4 1/2 years on average after the relapse; they resulted in death within less than 2 years in 11 (39.2%) and the survival rate was moderate (26.7%). The mean survival of the 12 patients now in remission is 7 years since the relapse and 13 years since the initial tumour.

Adenocarcinoma↗

Radiation-induced thyroid cancer.

Thyroid cancer was the first solid tumor that showed an increased incidence among the Japanese A-bomb survivors and recently published data indicated an increase of thyroid cancer among children in Belarus. The annual thyroid cancer rate between 1986 and 1989 was 4 cases and 2 years later a 14-fold increase was found. That study has several methodological weaknesses but is nevertheless alarming. The present paper reviews the current epidemiological knowledge on radiation-induced thyroid cancer, and discusses the methodological difficulties. It is concluded that low doses of brief gamma radiation induce thyroid cancer in juveniles. No study has yet proven a relationship between protracted low dose exposure and thyroid cancer or an increased thyroid cancer risk among adults after exposure to any form of ionizing radiation. Thyroid cancer seems to have a somewhat shorter latency period than other solid tumors and the dose-response relationship seems to be linear. The most important issues in radiation protection concerning thyroid cancer are the risk of a thyroid cancer following low dose and/or protracted exposure to ionizing radiation and following 131I exposure in childhood.

Adolescent↗

[The effect of thyroid hormone on the growth of thyroid cancer].

Thyroid cancer is well known to be hormone sensitive as well as breast cancer, prostatic cancer, and endometrial cancer of the uterus. Various experimental results suggest that the growth regulation for thyroid cancer, as well as the normal thyroid gland, appears to depend upon the TSH (Thyroid stimulating hormone) receptor on cell membranes. Differentiated thyroid carcinoma cells possess TSH receptor, although anaplastic carcinoma cells do not; therefore suppression therapy of TSH with thyroid hormone is considered to be effective against differentiated thyroid carcinoma. It has been recognized that some recurrent differentiated thyroid cancers cause regression in size in response to treatment with thyroid hormone. But the administration of the thyroid hormone after the operation for the differentiated thyroid carcinoma does not necessarily enhance the survival rate. To analyze the difference in survival rate is very difficult because of the excellent survival rate of thyroid cancer patients after the operation. It is hoped that further clinical study and laboratory investigation about suppression in adjuvant therapy for differentiated thyroid cancer will give us a conclusive answer.

Adolescent↗

Polymerase chain reaction in the detection of tumor cells: new approaches in diagnosis and follow-up of patients with thyroid cancer.

Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increasing frequency. In addition to other measures, diagnosis is based on fine-needle aspiration cytology examination. Recently, new assays using reverse transcription-polymerase chain reaction (PCR) are being tested to improve sensitivity and specificity of primary diagnosis and detection of recurrent thyroid cancer. In the preoperative diagnosis of thyroid cancer, several tissue- and/or tumor-specific mRNA have been described and in several cases, a higher sensitivity and specificity could be achieved using molecular techniques compared to conventional methods. In the postoperative follow-up of patients with thyroid cancer, conflicting data have been published and the use of PCR techniques revealed several problems of the molecular approach, which are based on some technical as well as biologic limitations. Despite these problems, which are discussed in detail in this review, molecular techniques may nevertheless improve the sensitivity and accuracy of fine-needle aspiration of thyroid nodules, fine-needle aspiration of metastases, and detection of recurrent disease in peripheral blood samples.

DNA, Neoplasm↗

Second primary cancers in thyroid cancer patients: a multinational record linkage study.

CONTEXT: Increasing incidence and improved prognosis of thyroid cancer have led to concern about the development of second primary cancers, especially after radioiodine treatment. Thyroid cancer can also arise as a second primary neoplasm after other cancers. OBJECTIVE: The objective of the study was to assess the risk of second primary cancer after thyroid cancer and vice versa. DESIGN: This was a multinational record linkage study. SETTING: The study was conducted at 13 population-based cancer registries in Europe, Canada, Australia, and Singapore. PATIENTS OR OTHER PARTICIPANTS: A cohort of 39,002 people (356,035 person-yr of follow-up) with primary thyroid cancer were followed up for SPN for up to 25 yr, and 1,990 cases of thyroid cancer were diagnosed after another primary cancer. MAIN OUTCOME MEASURES: To assess any possible excess of second primary neoplasms after thyroid cancer, the observed numbers of neoplasms were compared with expected numbers derived from age-, sex-, and calendar period-specific cancer incidence rates from each of the cancer registries, yielding standardized incidence ratios (SIRs). The SIR of second primary thyroid cancer after various types of cancer was also calculated. RESULTS: During the observation period, there were 2821 second primary cancers (all sites combined) after initial diagnosis of thyroid cancer, SIR of 1.31 (95% confidence interval 1.26-1.36) with significantly elevated risks for many specific cancers. Significantly elevated risks of second primary thyroid cancer were also seen after many types of cancer. CONCLUSION: Pooled data from 13 cancer registries show a 30% increased risk of second primary cancer after thyroid cancer and increased risks of thyroid cancer after various primary cancers. Although bias (detection, surveillance, misclassification) and chance may contribute to some of these observations, it seems likely that shared risk factors and treatment effects are implicated in many. When following up patients who have been treated for primary thyroid cancer, clinicians should maintain a high index of suspicion for second primary cancers.

Aged↗

Redifferentiation therapy in advanced thyroid cancer.

Thyroid cancer is a relatively common malignancy with an estimated prevalence of 250,000 in the U.S. A minority of patients have poorly differentiated thyroid carcinoma that is unresponsive to radioiodine therapy. Redifferentiation agents that 'reprogram' these tumors to concentrate radioiodine would be of great value in treating patients with advanced thyroid cancer. The retinoid isotretinoin is the most extensively studied of these agents. It appears that 20-40% of patients respond to isotretinoin treatment by concentration of radioiodine in metastatic tumors, but the clinical utility of this redifferentiation is still unclear. In vitro studies suggest that the retinoid receptors (RARbeta and RXRgamma) are required for this effect. Abnormal DNA methylation may be an early event in thyroid tumorigenesis and methylation of the sodium iodide symporter (NIS) may play a role in the loss of iodine concentration in these tumors. Inhibitors of methylation (5-azacytidine, phenylacetate and sodium butyrate) have been shown to increase NIS expression and iodine uptake in cell culture models, but published trials in humans are not yet available. Histone acetylation is required for efficient transcription of genes necessary for differentiated function. Proteins that cause histone deacetylation inhibit gene transcription and differentiated function. Inhibitors of histone deacetylation (depsipeptide, trichostatin A) have been shown to increase NIS expression and iodine uptake in poorly differentiated and undifferentiated cell lines. Phase II human trials are currently underway for depsipeptide. Finally, commonly used agents such as thiazolidinediones (diabetes) and HMG-CoA reductase inhibitors (hypercholesterolemia) have shown promise in preliminary in vitro studies in advanced thyroid cancer cell lines. Development of these and other novel agents for the treatment of advanced thyroid cancer is critical for us to treat an uncommon progression of a common malignancy.

Animals↗

Thyroid cancer.

Thyroid cancers are especially common in patients who have received irradiation to the head and neck region for benign diseases. Well-differentiated papillary and/or follicular carcinomas are the most common types of thyroid cancer. They grow slowly and have a very good prognosis when managed with an appropriate combination of surgical and medical therapy. Other types of thyroid cancer often require more intensive therapy and follow-up. It is especially important to evaluate relatives of patients with medullary thyroid cancer.

Adenocarcinoma↗

A conditionally replicative, Wnt/beta-catenin pathway-based adenovirus therapy for anaplastic thyroid cancer.

Thyroid cancer affects between 10,000 and 15,000 people per year in the US. Typically, this disease can be controlled with surgical resection and radioiodide treatment. However, resistance to these conventional therapies is observed in some patients, who develop intractable anaplastic thyroid cancer (ATC), for which no effective therapies exist. Recently, a sizable fraction of undifferentiated or poorly differentiated thyroid cancers were shown to contain mutations in beta-catenin, an oncogenic protein involved in the etiology of cancers of many tissues. We developed a conditionally replicative adenovirus (named 'HILMI') which, by virtue of TCF response elements drives E1A and E1B expression, replicates specifically in cells with an active Wnt/beta-catenin pathway. We show that several thyroid cancer cell lines, derived from undifferentiated or anaplastic tissues and possessing an active Wnt/beta-catenin pathway, are susceptible to cell killing by HILMI. Furthermore, viral replication in ATC cells as xenograft tumors in nude mice was observed, and prolonged survival of mice with ATC tumors was observed following administration of the HILMI therapeutic vector. The results warrant further development of this therapeutic approach for ATC patients.

Adenoviridae↗

[Isolated pelvic metastasis of thyroid cancer].

Thyroid cancer rarely metastasizes to the pelvis. We report a case where the metastasis was found two years before the thyroid cancer. Treatment included initial surgery with resection of the metastatic tumor and reconstruction of the acetabulum with bone cement, and secondly total thyroidectomy, node dissection and I131. Surgical treatment of locoregional recurrence had no influence on the clinical course leading to the patient's death. Early diagnosis of unique metastasis of a thyroid cancer is important in terms of prognosis and quality of life. This case is exceptional due to the unique bone metastasis and treatment options for acetabular metastases. Therapeutic options should be adapted according to algorithms reported in the literature.

Acetabulum↗

Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid.

The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. We have identified 4296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3843 subjects. Of the 2634 subjects who have been found, 1043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and our screening program, which began in 1974, we compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr.

Adult↗

6: Thyroid nodules and thyroid cancer.

Thyroid nodules are common clinically (prevalence, about 5%) and even more common on ultrasound examination (about 25%). About 5% of thyroid nodules are malignant. Most thyroid cancers are well-differentiated papillary or follicular tumours with an excellent prognosis (10-year survival, 80%-95%). The incidence of papillary thyroid cancer appears to be increasing on the east coast of Australia. Fine-needle aspiration biopsy of the thyroid is the most cost-effective diagnostic tool. Recommended initial management of all follicular carcinomas and of papillary carcinomas > 1.0 cm is total thyroidectomy followed by radioiodine ablation. Most patients should be managed postoperatively with doses of thyroid hormone sufficient to suppress plasma levels of thyroid-stimulating hormone. Recurrences can occur many years after initial therapy, and follow-up should be lifelong. Thyroid nodules are very common, but have a relatively low risk of malignancy

Adenoma↗

Surgical management of the neck in thyroid cancer.

Thyroid cancer is a relatively common clinical problem. The American Cancer Society has estimated 1,050,000 newly diagnosed cancers in 1999 in the United States, of which 16,000 are expected to be of thyroid origin. Although most thyroid cancers have an excellent prognosis as compared with other malignant tumors, it is estimated that approximately 1,225 deaths will be attributed to the disease [1].

Humans↗

Gene therapy for thyroid cancer.

Thyroid carcinomas are suitable targets for gene therapy because they can be highly lethal on one hand, while being susceptible to specific tumour targeting on the other hand. Several gene therapy modalities have been evaluated so far in experimental models of thyroid cancer, including tumour suppressor gene replacement, oncogene inhibition, suicide gene therapy, immunotherapy, antiangiogenesis, and viral oncolysis. All of these strategies have shown promising results, but clinical studies are lacking. Based on the clinical experience achieved in a pilot study in patients with advanced thyroid cancer and on clinical results in other types of solid cancer, it is suggested that combined gene therapy approaches, as well as multimodality therapeutic regimens, including gene therapy and conventional treatments, should be pursued to achieve clinically significant results.

Animals↗

Management of thyroid cancer.

Thyroid cancers are a diverse group of malignant disorders ranging from indolent micropapillary carcinoma, which has no effect on life expectancy, to anaplastic tumours, which are invariably fatal even with aggressive treatment. Although the estimated incidence has increased by 14.6% over the past 40 years, the estimated death rate has fallen by 21%, probably as a result of earlier diagnosis. The natural history of thyroid tumours is no longer a mystery, and the prognostic factors identified can predict outcome fairly accurately. Improvements in management have mostly depended on information from large retrospective series, though there are still many areas open to debate. There has been, however, a general acceptance that thyroid cancer should be managed by multidisciplinary teams in specialised units following evidence-based guidelines.

Adult↗

Cigarette smoking and the risk of thyroid cancer.

Thyroid cancer, whose aetiology is largely uncertain, has been negatively associated with cigarette smoking in a number of studies, possibly consistent with the greater occurrence of the disease in women than in men. This association was explored in the context of a Canadian case-control study of thyroid cancer. Newly diagnosed cases were identified primarily through provincial cancer registries in Canada and controls were identified from the general population. Data were collected through mailed questionnaires, yielding 1224 cases and 2659 controls. Reduced risk was observed for ever/never cigarette smoking (risk ratio estimate (RR) of 0.71 (95% confidence interval (CI)=0.60-0.83) for females and 0.77 (95% CI=0.58-1.02)) for males. Dose-response effects were observed with duration, quantity smoked and pack-years of exposure, although there was no decreasing protective effect with the age started smoking or years since stopped smoking. There is evidence of reduced risk for all histological subgroups. The protective effect of smoking may be due to a number of different mechanisms, including an effect on thyroid stimulating hormone and on oestrogen metabolism.

Adolescent↗

The Belgian and European Thyroid Cancer Registry. Belgian Thyroid Cancer Study Group.

Thyroid cancers frequently have a good prognosis, most of the patients are young and have a long life expectancy. Several hundreds of cases have to be observed over two to five decades before establishing studies of significant actuarial survival and determining the initial prognostic factors likely to characterize the disease. These elements necessitate the creation of a thyroid cancer registry gathering together, from several centres, the data and allowing a computerized multifactorial analysis. Each hospital will have the possibility to participate, with the help of the Belgian Campaign against Cancer, by means of a simple computerized system. Pathologists, endocrinologists, radiologists, radioisotope specialists and surgeons will coordinate their efforts to supply the necessary data to epidemiologists, statisticians and fundamental-researchers. Substantial progress can be expected providing all agree to an individual and collective effort which will have beneficial repercussions on the quality of patient care and the progress of knowledge. The Belgian Thyroid Cancer Study Group will permit our national medicine to meet the European requirements in this regard.

Adult↗

Contemporary management of thyroid cancer.

Thyroid cancer is a relatively common and frequently curable malignant neoplasm, accounting for nearly 2% of all new cancers diagnosed annually in the United States. The diagnostic and management options have evolved considerably in the past decade, and a current understanding of these trends in the standard of care have assumed an important consideration in the practices of head and neck surgeons and endocrinologists alike. We sought to review the epidemiology and pathology of the several types of thyroid cancer and to present our evidence-based management algorithm. Every effort was made to offer alternative treatment strategies and supporting data where available. In addition to reviewing well-established approaches to diagnosis and management, emphasis is placed on newer techniques, including minimally invasive thyroidectomy, molecular detection of disease propensity, and the use of recombinant thyrotropin prior to radioiodine ablation.

Adenocarcinoma, Follicular↗

A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening.

BACKGROUND: The Chornobyl accident in 1986 exposed thousands of people to radioactive iodine isotopes, particularly (131)I; this exposure was followed by a large increase in thyroid cancer among those exposed as children and adolescents, particularly in Belarus, the Russian Federation, and Ukraine. Here we report the results of the first cohort study of thyroid cancer among those exposed as children and adolescents following the Chornobyl accident. METHODS: A cohort of 32 385 individuals younger than 18 years of age and resident in the most heavily contaminated areas in Ukraine at the time of the accident was invited to be screened for any thyroid pathology by ultrasound and palpation between 1998 and 2000; 13 127 individuals (44%) were actually screened. Individual estimates of radiation dose to the thyroid were available for all screenees based on radioactivity measurements made shortly after the accident and on interview data. The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model. RESULTS: Forty-five pathologically confirmed cases of thyroid cancer were found during the 1998-2000 screening. Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate (P<.001), yielding an estimated excess relative risk of 5.25 per Gy (95% confidence interval [CI] = 1.70 to 27.5). Greater age at exposure was associated with decreased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant. CONCLUSION: Exposure to radioactive iodine was strongly associated with increased risk of thyroid cancer among those exposed as children and adolescents. In the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed, i.e., a reduction of 75% (95% CI = 50% to 93%). The study also provides quantitative risk estimates minimally confounded by any screening effects. Caution should be exercised in generalizing these results to any future similar accidents because of the potential differences in the nature of the radioactive iodines involved, the duration and temporal patterns of exposures, and the susceptibility of the exposed population.

Adolescent↗