Is the UICC/AJCC classification of primary tumor in childhood thyroid carcinoma valid?
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Biomedical subjects
Publications and source records attributed to C Reiners.
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During the course of tumor progression the differentiated morphologic and functional characteristics of differentiated thyroid carcinomas (DTC) disappear. This corresponds to more aggressive growth, metastatic spread, and loss of iodine uptake. Experimental data give strong evidence that differentiated functions of iodine metabolism can be reinduced by retinoic acids. Results of a study performed in patients with advanced DTC are presented. Twenty patients with DTC (eight follicular, seven papillary, five oxyphilic) were selected for treatment with retinoic acid 1.5 mg/kg body weight/day over 5 weeks. All patients had advanced tumor stages with prior operative and radioiodine treatment. Extensive tumor invasion, distant metastatic spread, or insufficient or no radioiodine uptake precluded any conventional therapeutic option. The aim was to assess the changes under retinoid treatment. Iodine uptake increased in eight patients (three follicular, three papillary, two oxyphilic). Thyroglobulin (TG) as parameter for tumor mass and differentiation increased in 12 (63%) patients, decreased in 6 (32%), and did not change in 1 (5%). Retinoids do have an effect on differentiation status of DTC, reinducing iodine uptake in 50% of patients. TG levels do not always parallel a response in iodine uptake.
INTRODUCTION: There have been only a few studies on differentiated childhood thyroid cancer (DTC) in children and adolescents. METHODS: We analyzed the characteristics of DTC with respect to age, gender and histology in 114 patients under 18 years of age. In a questionnaire-based survey, data of 114 patients, aged between 3 years and 18 years, was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated, and the prognostic effect of age, gender, histology, multicentric growth, tumor stage and N-status on distant metastases was tested using multivariate discriminant analysis. Between-group comparison was performed using student t-test and chi-squared test. RESULTS: The incidence of DTC in females was higher than in males with a peak of female:male ratio at puberty, which was more pronounced in children with papillary thyroid cancer, but not with follicular thyroid cancer. Papillary thyroid cancer was associated with more advanced disease (P=0.009), more lymph-node involvement (P=0.007) and more distant metastases (P=0.02) compared with follicular thyroid cancer. Multivariate analysis showed advanced tumor stage as the only significant factor (P=0.02) associating with distant metastasis. CONCLUSION: It can be concluded that in children and adolescents: 1. The incidence of papillary thyroid cancer is higher in females than males, with a peak at puberty. 2. The only significant factor associated with distant metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently associated with lymph-node involvement, distant metastases and advanced tumor stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular type.
UNLABELLED: The results of serial dimercaptosuccinic acid (DMSA) imaging over 5 years are reported in 287 children with severe vesico-ureteral reflux entered into the European Branch of the International Reflux Study in Children. The children were randomly allocated to medical (n=147) or surgical (n=140) management and DMSA studies were performed during the follow up period at least 6 months after any urinary tract infection. Abnormal images were classified into four types: (1) large polar hypodensity with normal renal outline; (2) peripheral photon deficient defect(s) in a non-deformed kidney; (3) small renal image with normal contour; and (4) peripheral defect(s) with resultant irregularity of the renal outline. The DMSA findings were abnormal at entry in 235 (82%) with no difference in incidence or severity between the two treatment groups. During follow up, deterioration was observed in 25 medically and 23 surgically treated patients and comprised image deterioration alone in 17, image deterioration with corresponding reduction in differential function in 16 and reduction in relative function without image change in 15, with similar distribution between the two treatment groups. Deterioration was more frequent in children entering the study under the age of 2 years and in those with grade IV rather than grade III reflux. These findings, showing no difference in outcome between children managed surgically or medically, are consistent with the radiological results already published. CONCLUSION: In the International Reflux Study the DMSA scintigraphic data showed no difference in outcome between children managed surgically or medically.
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Assessment of iodine deficiency and monitoring of iodine supplementation programs demands rapid, simple and cost-effective methods for the determination of urinary iodide concentrations. We propose a rapid test based on the iodide-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine by peracetic acid/H2O2 to yield colored products. The color of the chemical reaction is compared with color categories of a pictogram corresponding to three ranges (<10, 10-30, and >>30 microg/100 mL) of iodide concentrations. The test is very easy to perform and does not require any instrumentation or apparatus. Sample preparation is simple and consists in the removal of interfering substances by disposable columns, 65 x 10.5 mm, packed with specifically prepared activated charcoal. For comparison with a reference method for measuring urinary iodide (HPLC), we determined the iodide concentrations of 370 random (untimed) urine samples from consecutive patients by both HPLC and the rapid test. The results obtained by both methods are in close agreement with respect to classification of the samples according to the above three ranges, with a maximum difference of <5% for each range. This rapid test is therefore very well suited to epidemiological surveys of iodine deficiency especially in developing countries.
This work describes an optimization of a simple photometric determination of iodine concentrations in urine using a modified ceric arsenite method with ammonium persulfate as oxidant. By means of this sensitive method iodine concentrations can be determined in very small specimens (50 microL). Urine samples (105) collected from a mixed population, were analyzed for urine iodine content by the optimized ammonium persulfate method, a Technicon Autoanalyzer II and a paired-ion-RP HPLC. We found that the precision of this optimized ammonium persulfate method yields inter assay CVs of <10% for urinary iodine concentrations >10 microg/dL. Recovery of [123I]iodide added to urine in vitro was 100.9 +/- 2.4%. The detection limit was 0.0029 microg iodine. There was a high correlation between all three methods (r > 0.94 in any case) and the interpretation of the results was consistent. We conclude that this simple, manual ammonium persulfate method is suitable for urinary iodine analysis and can be performed in any routine clinical laboratory.
X-ray fluorescence analysis is based on the principal that the electron structure of stable iodine in the thyroid is excited by Americium-241 gamma rays to emit a characteristic fluorescence radiation which is proportional to the amount of iodine present in the gland. A stationary measuring system consisting of a 11.1 GBq Am-241 source and a high-purity Germanium detector with spectrum analyser has been improved by a PC guided method for sonographic definition of the measuring volume. The lower limit of detectibility of the system corresponds to 0.01 mg of Iodine per ml of thyroid volume; the in vivo precision given as coefficient of variation amounts to 15%. The thyroid is exposed with a radiation dose of 6 microSv per measurement. First studies with this improved system carried out in 50 female volunteers between 20 and 40 years of age with normal thyroid volumes resulted in a mean iodine concentration of the thyroid of 0.665 +/- 0.304 mg/ml. The mean iodine excretion in urine was normal with 10.8 +/- 10.4 microg/dl.
The most important information in the determination of the status of iodine nutrition of a population comes from the measurement of the urinary excretion of iodine. Several methods are available for measuring urinary iodine. The choice among methods depends on the intended application, the number of samples, the cost and the technical capability. Epidemiological field studies demand simple, rapid and cost-effective methods. Suitable for these applications are the rapid urinary iodide test and the ammonium persulfate oxidation method which gives comparable results to the chloric acid method without having the drawbacks of being hazardous and explosive. In research studies however, sophisticated automated technology like the Technicon Autoanalyzer or Paired-Ion Reversed Phase HPLC are used in which the high cost of instrumentation are outweighed by the benefits of processing a large number of samples with high accuracy and minimal technician time. For determining serum inorganic iodide (SII) the HPLC assay is the method of choice, because contaminations from the protein bound iodine fraction do not interfere with the detection process. The clinical relevance of the measurement of SII is limited, but allows the calculation of the absolute iodine uptake which has great value in pathophysiologic studies.
Precision, long-term stability, linearity and accuracy of the x-ray peripheral quantitative computerized tomographic (pQCT) bone scanner XCT 3000 (Norland-Stratec Medical Sys.) were evaluated using the European Forearm Phantom (EFP). In vivo measurements were assessed using a standardized procedure at the distal femur and the distal tibia. In the patient-scan mode, the spatial resolution of the system was 1.04 +/- 0.05 lp/mm as measured at the 10% level of the modulation transfer function (MTF). The contrast-detail diagram (CDD) yielded a minimal difference in attenuation coefficient (AC) of 0.07 cm(-1) at an object size of 0.5 mm. The effective dose for humans was calculated to be less than 1.5 microSv per scan. Short-term precision in vivo was expressed as root mean square standard deviation of paired measurements of 20 healthy volunteers (RMSSD = 0.5%). At the distal femur total volumetric density (ToD) and total cross-sectional area (ToA) were found to be less sensitive to positioning errors than at the distal tibia. Structural parameters like the polar cross-sectional moment of inertia (CSMIp) or the polar cross-sectional moment of resistance (CSMRp) showed a good short-term precision at the distal femur (RMSSD = 1.2 and 1.4%). The relation between the two skeletal sites with respect to CSMIp or CSMRp showed a high coefficient of determination (r2 = 0.77 and 0.74).
Currently, fine-needle aspiration cytology is a valuable tool in the routine diagnosis of suspicious thyroid nodules. We present a very sensitive method for the molecular analysis of the expression of several genes important for normal thyroid function in parallel to the cytological diagnosis. We adapted reverse transcriptase polymerase chain reaction (RT-PCR) to amplify thyroid-typical mRNAs in samples of thyroid carcinoma cells as small as those obtained by fine-needle aspiration biopsy (FNAB), ie, 100-1000 cells, and applied this procedure to four routinely taken FNABs. Gene products such as thyroglobulin (Tg), thyroid-stimulating hormone-receptor (TSHr), sodium/iodide-symporter (NIS), type I iodothyronine-5'-deiodinase (DI), and type II iodothyronine-5'-deiodinase (DII) were analyzed. To establish RT-PCR protocols, serial dilutions of follicular thyroid carcinoma cells, FTC-133, which express these genes at low levels, were initially used for RNA isolation. Successful RNA isolation and reverse transcription were checked by the amplification of beta-actin mRNA. We detected the mRNAs coding for Tg in as little as 10 cells, for NIS in 100 cells, and for TSHr, DI, and DII in 10,000 cells. After preparing cytological smears of four routinely taken FNABs, all above-mentioned thyroid-typical mRNAs were observed by using the material remaining in the needle for RNA isolation followed by RT-PCR. This method offers the possibility of obtaining two different types of information from the same routinely taken thyroid FNAB: the cytological diagnosis and the expression pattern of several diagnostically relevant genes. Therefore, a more specific diagnosis could be rendered in the preoperative state, and may lead to more specific therapy.
Radionuclide ventriculography (RNV) is an established method of evaluating cardiotoxic side-effects of chemotherapy. The image quality of RNV depends on labelling yields obtained after red blood cell (RBC) labelling with 99Tc(m)-pertechnetate and has an influence on the evaluation of the left ventricular ejection fraction (LVEF). Several drugs and certain parameters of RBC labelling are known to have a detrimental effect on the labelling yield, but often the reason for poor image quality remains unclear. The aim of this study was to determine the effect of chemotherapeutic agents on LVEF evaluation. The chemotherapeutic medications and RNV data of 116 patients were noted. The patients underwent 205 RNV examinations (up to 7 RNV follow-up examinations) consisting of rest and stress studies. Ten patients with a poor labelling yield after in vivo labelling received an additional RNV study after in vitro labelling. The effects of commonly used anticoagulants and chemotherapeutic drugs on labelling yields were also investigated in experiments on in vitro RBC labelling. In vitro labelling had the advantage of better detection of pathological alterations in left ventricular motility, but often improved evaluability only slightly. The administration of corticosteroids showed an unexpected positive correlation with image quality (Spearman correlation coefficient: prednisone, 0.42403, P = 0.0013; prednisolone, 0.45629, P = 0.0286) and labelling yield (prednisolone, 0.65466, P = 0.0024), whereas idarubicin showed a negative correlation with image quality (-0.53364, P = 0.005). A slight positive correlation of prednisolone with LVEF at rest (0.45425, P = 0.0197) was also noted. Using our evaluation software, the manual contour method was found to be superior to the automatic determination of the left ventricular contour. Cycle ergometry alone caused a significant deterioration in image quality. The in vitro results suggested a negative influence of epirubicine on labelling yields at very high concentrations (10(-3) M). Our main result was that a clinically adequate study is possible in patients with moderate image quality and labelling yields. Furthermore, the administration of corticosteroids had a positive impact on image quality.
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the basal ganglia, which may be visualized by single photon emission computed tomography (SPECT) in combination with the cocaine analog methyl-3-beta-(4-beta[123I]iodophenyl)tropane-2beta-carboxylate ([123I]beta-CIT). The aim of our study was to correlate findings of SPECT with clinical data of 34 previously untreated, idiopathic parkinsonian patients [age: 59.58+/-10.03 (mean+/-SD) years; Hoehn and Yahr Scale (HYS) mean range: 1.97+/-0.83, ranges I-III; Unified PD Rating Scale 3.0 (UPDRS, 30.64+/-18.68) and 15 healthy controls (age 47.93+/-10.47 years). SPECT scans were performed with a single-head gamma-camera 24 h after intravenous injection of [123I]beta-CIT. Comparison of the striatum/cerebellum (S/C) ratio of [123I]beta-CIT uptake of controls and parkinsonian subjects, subdivided according to their HYS range, was significant. No influence of age or sex was observed. Significant correlations were found between scores of the HYS, UPDRS parts I-III, part II, part III, and the S/C ratio of [123I]-CIT uptake. Moreover, SPECT with the radiotracer [123I]beta-CIT revealed side-to-side differences in parkinsonian patients and significant associations to contralateral clinical extrapyramidal symptomatology. Our data show that SPECT with [123I]beta-CIT is a valuable tool for estimating disease severity in PD.
Assessment of iodine deficiency and monitoring of iodine supplementation programs demand rapid, simple, and cost-effective methods for the determination of urinary iodide concentrations. We propose a semiquantitative rapid test, based on the iodide-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine by peracetic acid/H2O2, to yield colored products. The color of the chemical reaction is compared with color categories of a pictogram corresponding to three ranges: <100, 100-300, and >300 microg/L (<0.79, 0.79-2.36, and >2.36 micromol/L) of iodide concentrations. The test is very easy to perform and does not require any instrumentation or apparatus. Sample preparation is simple and consists of the removal of interfering substances by disposable columns, 65 x 10.5 mm, packed with purified activated charcoal. For comparison with a reference method for measuring urinary iodide, by high-performance liquid chromatography, we determined the iodide concentrations of 370 random (untimed) urine samples from consecutive patients by both high-performance liquid chromatography and the rapid test. The results obtained by both methods are in close agreement, with respect to classification of the samples according to the above three ranges, with a maximum difference of less than 5% for each range. Median (y) values of a given distribution of urinary iodide concentrations can be calculated from the percent (x) of samples below 100 microg/L (0.79 micromol/L) using the regression equation: y = 179.78 - 1.60x. This rapid test, therefore, is suited to epidemiological surveys of iodine deficiency, especially in developing countries.
OBJECTIVE: Several studies have suggested that iodine may influence thyroid hormone status, and perhaps antibody production, in patients with autoimmune thyroid disease. To date, studies have been carried out using large amounts of iodine. Therefore, we evaluated the effect of small doses of iodine on thyroid function and thyroid antibody levels in euthyroid patients with Hashimoto's thyroiditis who were living in an area of mild dietary iodine deficiency. METHODS: Forty patients who tested positive for anti-thyroid (TPO) antibodies or with a moderate to severe hypoechogenic pattern on ultrasound received 250 microg potassium iodide daily for 4 months (range 2-13 months). An additional 43 patients positive for TPO antibodies or with hypoechogenicity on ultrasound served as a control group. All patients were TBII negative. RESULTS: Seven patients in the iodine-treated group developed subclinical hypothyroidism and one patient became hypothyroid. Three of the seven who were subclinically hypothyroid became euthyroid again when iodine treatment was stopped. One patient developed hyperthyroidism with a concomitant increase in TBII titre to 17 U/l, but after iodine withdrawal this patient became euthyroid again. Only one patient in the control group developed subclinical hypothyroidism during the same time period. All nine patients who developed thyroid dysfunction had reduced echogenicity on ultrasound. Four of the eight patients who developed subclinical hypothyroidism had TSH concentrations greater than 3 mU/l. In 32 patients in the iodine-treated group and 42 in the control group, no significant changes in thyroid function, antibody titres or thyroid volume were observed. CONCLUSIONS: Small amounts of supplementary iodine (250 microg) cause slight but significant changes in thyroid hormone function in predisposed individuals.
AIM: Patients exhale I-131 after radioiodine therapy. In this study we quantify the amount of radioactivity and resulting thyroid doses found in people living in close contact to patients treated with I-131 after their release from a therapy ward. METHODS: For 31 relatives of 25 patients treated with I-131 the incorporation was monitored using the thyroid probe of a whole body counter. These values are used for a determination of thyroid doses. RESULTS: 11 of the 31 monitored persons had a thyroid activity of less than the minimal detectable activity of 13 Bq. The mean value of the remaining 20 people was 104 Bq in the thyroid resulting in a mean thyroid dose of 0.2 mSv (Maximum: 2 mSv). CONCLUSION: The intake of I-131 for persons in close contact to patients after dismissal from a therapy ward is low. In no case an effective dose exceeding 1 mSv was observed.
UNLABELLED: The objective of this study was to estimate the reproducibility of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) clearance calculated using a single-sample method. METHODS: One hundred forty-seven patients with urological or ear, nose and throat cancer were analyzed in a retrospective study. Each patient had at least two clearance studies with 99mTc-MAG3 before chemotherapy treatments to monitor renal function. Up to five clearance studies per patient were considered. The reproducibility was estimated by comparing two consecutive investigations. Pairs of investigations with a change in split renal function of more than 5% or an interval of more than 50 days were excluded. Clearance was determined using the Bubeck method. For each pair of consecutive clearance data, the difference between the first and the second measurements was expressed as a percentage of the mean value of the two measurements. The mean of these normalized differences represents the systematic deviation, and the s.d. represents the reproducibility of the compared clearances. RESULTS: After the selection, 242 pairs of consecutive clearance data remained for comparison. Significantly different clearances were observed only between investigations 0 and 1 and between 4 and 5. The systematic deviation of these comparisons totaled -3.8% and -5.7%, respectively. In the other comparisons, no significant deviation induced by the chemotherapy was found. The reproducibility calculated for all comparisons totaled 11.7%. CONCLUSION: The error of reproducibility of 99mTc-MAG3 clearance using the Bubeck method was < or =11.7%. This was an acceptable value, taking into account the greater fluctuation of tubular function compared with the glomerular filtration rate.