Completion total thyroidectomy in children with differentiated thyroid cancer

INTRODUCTION: The optimal surgical treatment of children with differentiated thyroid cancer remains an important point of discussion. Especially the need for completion operation is questioned in young patients. Our objective was to examine the rate of residual neoplastic disease after non radical initial operation. MATERIAL AND METHODS: From the 235 children diagnosed with differentiated thyroid cancer, 131 (56%) needed completion operation due to incomplete primary surgery. Completion operation involved thyroid bed, lymph nodes or both respectively in 91 (39%), 13 (6%) and 27 (11%) cases. Risk factors responsible for residual disease were evaluated by means of logistic regression analysis. RESULTS: Residual disease was detected in 46 (35%) of reoperated children (25% in thyroid bed and 85% in lymph node of lateral neck compartment). Sex and age did not influence the risk of residual disease in thyroid bed or lymph nodes. Papillary type of cancer and multifocality increased risk of residual disease in thyroid bed respectively by the factor of 15 (95% CI: 2-125) and 2.3 (95% CI: 1.2-4.4). Infiltration of thyroid capsule did not correlate with the risk of residual disease. Lymph node metastases in primary operation increased risk of residual disease by the factor of 16 (95% CI: 1.2-245). Histopathology, multifocality of primary tumour or infiltration of lymph node capsule did not influence the risk of residual disease in lymph nodes of lateral neck compartment. CONCLUSIONS: In children with differentiated thyroid cancer residual disease is diagnosed in about 1/3 of non radically operated cases. This high incidence justifies completion operations. The risk of residual disease is significantly increased in papillary thyroid cancer, multifocal tumours and cases with lymph node metastases.     

Clinical significance of serum thyroglobulin and antithyroglobulin antibody in differentiated thyroid cancer after thyroid ablation

Serum thyroglobulin (Tg) is a suitable marker for differentiated thyroid carcinoma following total thyroid ablation. Between 1998 and 2003, serum samples from 715 papillary and 179 follicular tumor patients treated with total/nearly total thyroidectomy and radioiodine ablation therapy were collected. According to the "Guidelines for Oncotherapy in Hungary", serum Tg, antithyroglobulin antibody (TgAb), TSH and FT4 levels were measured in periods of 3 months following the first treatment and of 6 months after 2 years. In the present work the prognostic value of Tg and TgAb data of cancer patients with hormone substitution therapy were evaluated individually and retrospectively. Serum Tg and TgAb concentrations were measured with a highly sensitive immunoradiometric (IRMA) method, and with a second generation, broad epitope specificity competitive radioimmunoassay, respectively. TSH levels determined by fourth generation LIAISON kit were in a range of 0.05-0.10 mIU/L. Accuracy of measuring of Tg <1 ng/ml made it possible to select the low cut-off level (Tg <2 ng/ml) following total thyroidectomy. In the predominant part of TSH-suppressed patients (746/774, 96%) the serum Tg concentration was below the cut-off level of 2 ng/ml. The sensitivity of Tg determination in 59 TSH-suppressed thyroid cancer patients with lung and bone metastases was as high as 86 to 100%. On the contrary, the number of false negative data was high in cases with lymph node metastases of papillary cancer, and sensitivity did not exceed 62%. Specificity and sensitivity of Tg in TgAb negative patients were 91 to 100%. Based on our results it could be concluded that measuring of Tg and TgAb, using a current IRMA method and a second generation RIA kit, proved to be effective tools for the postoperative monitoring of differentiated thyroid tumours. It has to be noted that determination of TgAb is highly recommended for the adequate interpretation of serum Tg levels. Persistently high and/or increasing serum TgAb concentration with low Tg result had a diagnostic value during the follow-up and can be connected with the recurrence or persistence of the differentiated thyroid cancer.     

TSH-suppressive treatment in differentiated thyroid cancer. A dogma under review

TSH-suppressive therapy (ST) is part of the treatment protocol for differentiated thyroid carcinoma (DTC). There is however little evidence of its clinical effectiveness. On the other side, ST is not free from side effects related to the subclinical hyperthyroidism status induced in patients for a long time period. Because of this, widespread use of ST in all patients has recently been questioned, and individualized treatment based on the characteristics of each particular case has been proposed. Action of thyroid hormones (THs) depends on their binding to specific nuclear receptors. However, a second pathway mediated by a membrane receptor located in integrin α(V)β(3) has recently been established. It has been postulated that the proliferative and angiogenic effects attributed to THs would depend on this second mechanism. It is not known whether the tumorigenic action shown in other neoplasms may have an impact on DTC. The objective of this study was to review the relationship between ST and cancer, particularly as regards tumor evolution and occurrence of second primary neoplasms. One of the future challenges in the field of DTC will be to establish the specific role of TSH and THs in malignant thyroid cells, in order to be able to define more optimized therapeutic schemes.     

Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer

We aimed to investigate insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), insulin-like growth factor binding protein-3 (IGFBP-3) genotypes, which are thought to be involved in the pathogenesis of many solid tumors and have thus far not been studied in patients with differentiated thyroid cancer (DTC). The study consisted of 93 patients diagnosed with DTC (79 females, 14 males) and 111 healthy control subjects (63 females, 48 males). The anthropometric measurements, lipid profiles, thyroid function tests and homeostatic model assessment (HOMA) as an indicator of insulin resistance (IR) of all patients were recorded. In addition IRS-1, IRS-2 and IGFBP-3 gene polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. Hardy–Weinberg equilibrium was tested for each gene polymorphisms, and genetic effects were evaluated by the Chi Square test and multiple logistic regression. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, waist circumference and serum total cholesterol levels were significantly higher in patients with DTC than in the control group. There was no difference between the two groups with respect to IRS-1, IRS-2 and IGFBP-3 gene polymorphisms. In addition, these gene polymorphisms were found to have no effect on lymph node metastases or tumor staging. While, obesity and increased HOMA-IR may be risk factors in DTC development, we suggest that IRS-1, IRS-2 and IGFBP-3 gene polymorphisms do not play an important role in pathogenesis of DTC.     

The practice and principles of community-based wildlife management in Zimbabwe: the CAMPFIRE programme

This paper describes Zimbabwe's wildlife-based CAMPFIRE programme. It suggests that community-based natural resource management is a potential solution to the inter-linked problems of poverty and conservation if it is based on sound management principles that also incorporate transparency, accountability and democracy because the unit of management is a community.This first section suggests that many of the causes of these natural resource problems in communal lands are a result of the failure of mechanisms to price and allocate resources efficiently. The second section describes the evolution of CAMPFIRE, while the third section summarizes the principles that underpin the programme. The fourth section discusses the governance of natural resources and describes the process by which rights to wildlife have been devolved. This emphasizes how important political and administrative systems are to wildlife conservation. CAMPFIRE can be viewed as a five-step process: getting an enabling political, legal, administrative and economic environment; creating awareness and a demand for the programme; generating revenues; using these revenues effectively; and, finally, setting in place the institutions and capacity for locally-based natural resource management. The first four sections of the paper deal with step on — the enabling environment, what it is and how it came about. The final section describes the actual implementation of the programme and is rather brief.     

Relapse of differentiated thyroid carcinoma in low-risk patients

INTRODUCTION: The low incidence of relapse in differentiated thyroid carcinoma (DTC), primarily treated by total thyroidectomy and (131)I ablation, stimulates the search for optimal follow-up algorithms which do not include too many tests but are not connected with a risk of missing early recurrence. The aim of the study was to analyze the impact of the routine follow up examinations for early detection of DTC recurrence in low risk DTC patients. MATERIAL AND METHODS: The group consisted of 617 DTC patients diagnosed in 1995-1996. In 513 (83%) total thyroidectomy was performed. 449 (73%) received ablative (131)I therapy. After primary approach complete remission (CR) was stated in 453 (73%), persistent disease in 116 (19%), asymptomatic hyperthyroglobulinaemia in 14 (2%). Patients with CR constituted the low risk group analyzed in this study. The median follow up was 4.16 yrs. RESULTS: Recurrent disease appeared in 28 (6%) patients (23 locoregional, 9 distant metastases, both in 4). Serum Tg (thyroglobulin) level at the moment of relapse diagnosis was detectable in 44% while neck sonography was the first examination to detect recurrence in 56% of cases. CONCLUSION: In the selected group of DTC patients treated by radical primary approach and showing a low risk of recurrence only half of all relapse cases are diagnosed by the rise of serum Tg level. Regular sonography contributes to the second half of diagnoses. Thus, a special weight should be put on neck sonography as the important element of regular follow up in low risk DTC patients.     

Influence of the endogene TSH stimulation of thyroid volume increase in the patients after total thyroidectomy due to differentiated thyroid cancer

INTRODUCTION: The treatment-of-choice for differentiated thyroid carcinoma (DTC) is a total thyroidectomy with subsequent radioiodine therapy. In order to increase an iodine uptake in thyroid tissue remnants, the L-thyroxine withdrawal is required. It is recommended to achieve TSH levels higher than 25 mU/ml. As TSH is a known key factor in thyroid cell proliferation regulation, prolonged stimulation of the cells during L-thyroxine withdrawal can be a causative factor for a re-growth. Our aim was to assess the degree of thyroid re-growth in the patients after total thyroidectomy due to DTC and its possible clinical implications. MATERIAL AND METHODS: 23 patients operated due to papillary and follicular thyroid cancer were included into the study. Biochemical determinations and ultrasound thyroid imaging were performed (TSH, Tg) during suppressive L-thyroxine therapy as well as 4-5 weeks after the withdrawal. RESULTS: The mean volume of thyroid tissue remnants increased after withdrawal for substantial 30.1%. The difference was extremely significant. CONCLUSIONS: L-Thyroxine withdrawal in the patients after total thyroidectomy due to DTC can cause re-growth of the tissue remnants. The phenomenon may be of a clinical significance in the selected cases influencing therapeutic decisions.     

The role of surgery in the management of thyroid cancer.

This is a review of one surgeon''s personal experience with 85 patients with thyroid cancer treated over a 20-year period. The data confirm that for papillary thyroid tumours, with rare exceptions, the prognosis is excellent. Anaplastic lesions, however, are consistently lethal. Follicular carcinoma and medullary carcinoma fall between these extremes. A simple clinical classification is offered as a guide to operative management and a reliable index of prognosis. Patients with clinically apparent, "manifest cancer" have serious, life-threatening disease; many such patients die of their disease. Patients with "neck lumps not yet diagnosed" usually have papillary carcinoma; their prognosis is excellent. Patients whose thyroid tumours fall into the category of "malignant nodule" or "pathologist''s cancer" are particularly fortunate: in this series no such patient has died. The importance of age in relation to thyroid cancer is also confirmed: non of the patients first treated before the age of 40 years has died of cancer. For young patients with favourable disease the author recommends conservative surgical treatment, which avoids cosmetic deformity or functional disability, to be followed by administration of levothyroxine to suppress production of thyroid=stimulating hormone. For patients with "unfavourable" thyroid cancer valuable palliation can often be achieved by a combination of surgery and irradiation. Survival rates for the total series are 76% at 5 years and 60% at 10 years.     

The early treatment results of well differentiated thyroid cancer and its dependence on chosen factors

INTRODUCTION: The aim of the study was to estimate the influence of a thyroid remnants' volume, postsurgical concentration of thyroglobulin and radioiodine dose on the early treatment efficacy of well differentiated thyroid cancer. MATERIAL AND METHODS: We retrospectively analyzed 91 patients (76 females, 15 men) with well differentiated thyroid cancer. RESULTS: Histological classification revealed 68.1% (62/91) papillary thyroid cancers, 25.3% (23/91) follicular thyroid cancers, and 6.6% (6/91) oxyphilic thyroid cancers. Among the group, 74 (81.3%) patients reached the remission criteria and the remaining 17 patients (18.7%) showed biochemical and morphological evidence of metastatic disease. The remission was obtained in 100% of patients in stage I of the disease, 68.4% - in stage II, 78.6% - in stage III and 33.3% in stage IV. The total radioiodine dose used in patients with remission, did not differ from the dose used in patients without remission. We did not observe the influence of remnant's volume on treatment efficacy, however larger remants required higher dose of radioiodine to obtain the remission. Patients with remission had lower postsurgical thyroglobulin concentration than patients without remission. (22.2 vs. 103.3 ng/ml; p = 0.00025). CONCLUSIONS: Early treatment results of well differentiated thyroid cancer depend on the clinical stage, and postoperative serum thyroglobulin level measured after endogenous TSH stimulation. Early treatment results are not dependent on age, sex, histological type of thyroid cancer, the dose of radioiodine used in brackets of 60-150 mCi and additional diseases. Total thyroidectomy is equally efficient as near total.     

Dependency of the remnant 131I-NaI biokinetics on the administered activity in patients with differentiated thyroid cancer

PurposeTo study the dependency of the effective half-life on the administered activity and the correlation between the time-integrated activity and the remnant uptake at 2d and 7d in patients treated for DTC with 1.11 GBq, 3.7 GBq or 5.55 GBq of ¹³¹I-NaI.MethodsNinety-two patients undergoing total thyroidectomy and lymph node removal were included. If cancer had not spread to lymph nodes, patients received 1.11 GBq of ¹³¹I-NaI when the lesion maximal diameter was smaller than 4 cm, and 3.7 GBq for bigger sizes. If cancer had spread to lymph nodes patients received 5.55 GBq. There were 30, 49 and 13 patients respectively treated with 1.11 GBq(Group 1), 3.7 GBq(Group 2) and 5.55 GBq(Group 3). Two SPECT/CT scans were performed at 2d and 7d after radioiodine administration for each patient to determine the thyroid remnant activities and effective half-lives of the radioiodine.ResultsStatistical analysis showed significant differences (p < 0.05) in the effective half-life among patients treated with 1.11 GBq, 3.7 GBq and 5.55 GBq. A high positive correlation (ρ > 0.95) was found between the time-integrated activity and the remnant activity at 2d for the three groups of patients.ConclusionsThere were significant differences in the effective half-life of the radioiodine in remnants of patients treated with activities of 1.11 GBq, 3.7 GBq or 5.55 GBq. The high positive linear correlation found between the time-integrated activity and the remnant activity at 2d for the three groups of patients indicate that the time-integrated activity could be estimated from one time-point.     

Preablative stimulated thyroglobulin in predicting dynamic risk stratification after 1 year in patients with differentiated thyroid cancer

The aimThe aim of the study is to establish the utility of stimulated preablative stimulated thyroglobulin (ps-Tg) as a predictor of response to therapy and to determine a possible cut-off for ps-Tg as prognostic tool.Patients and methodsA total of 73 consecutive patients who underwent total thyroidectomy and remnant ablation with radioactive iodine therapy (RIT) were reviewed retrospectively. Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The ps-Tg values were compared among the groups. ROC curve analysis was performed.ResultsThe mean age at diagnosis was 43.85 (range: 17–75) with a female-to-male ratio of 4.6. Ps-Tg value after total thyroidectomy and before RIT ranged from 0,1 to 256 ng/mL. When patients were restaged, 74% had excellent response to treatment, 12.3% indeterminate and 13.7% incomplete response 1 year after initial therapy. ROC curve analysis showed that the optimal cut-off for ps-Tg was 15 ng/mL with a sensivity of 61%; a specificity of 87%; PPV of 61% and NPV of 87%. Among the group of patients showing an excellent response to treatment after 1 year, 87% had ps-Tg < 15 ng/mL.ConclusionPs-Tg before RIT is associated with dynamic risk stratification at 1 year after therapy in patients with DTC. Higher ps-Tg levels were found in patients that had indeterminate, and particularly incomplete, response.     

Synthesis of extracellular matrix glycoproteins by a differentiated thyroid epithelial cell line

We examined the synthesis of extracellular matrix macromolecules by the differentiated rat thyroid epithelial cell line FRTL-5. As shown by electron microscopy, the extracellular material produced by these cells is deposited at the basolateral surface and focally organized in the form of a basement membrane. Biochemical and biosynthetic studies demonstrated that laminin, type IV collagen, and fibronectin are synthesized and deposited in the culture monolayer. Secretion of fibronectin into the culture medium also occurred. By immunofluorescence we observed some peculiarities in the distribution patterns of the basement membrane glycoproteins; while fibronectin and laminin had an almost superimposable distribution, type IV collagen displayed a rather different pattern. Type IV collagen and laminin localization at sites where extracellular material was detected was confirmed by immuno electronmicroscopy using the protein A-colloidal gold technique. The results indicate that under appropriate culture conditions the differentiated thyroid epithelial cell line FRTL-5 synthesizes, secretes and organizes an extracellular matrix where some basement membrane glycoproteins are present.