A nonparametric measure of contrast in x-ray images.

Objective.We propose a nonparametric figure of merit, the contrast equivalent distance CED, to measure contrast directly from clinical images.Approach.A relative brightness distanceδis calculated by making use of the order statistic of the pixel values. By multiplyingδwith the grey value rangeR, the mean brightness distance MBD is obtained. From the MBD, the CED and the distance-to-noise ratio DNR can be derived. The latter is the ratio of the MBD and a previously suggested nonparametric measureτfor the noise. Since the order statistic is independent of the spatial arrangement of the pixel values, the measures can be obtained directly from clinical images. We apply the new measures to mammography images of an anthropomorphic phantom and of a phantom with a step wedge as well as to CT images of a head phantom.Main results.For low-noise images of a step wedge, the MBD is equivalent to the conventional grey value distance. While this measure permits the evaluation of clinical images, it is sensitive to noise. Therefore, noise has to be quantified at the same time. When the ratioσ/τof the noise standard deviationσtoτis available, validity limits for the CED as a measure of contrast can be established. The new figures of merit can be calculated for entire images as well as on regions of interest (ROI) with an edge length not smaller than 32 px.Significance.The new figures of merit are suited to quantify the quality of clinical images without relying on the assumption of a linear, shift-invariant system. They can be used for any kind of greyscale image, provided the ratioσ/τcan be estimated. This will hopefully help to achieve the optimisation of image quality vs dose required by radioprotection laws.

A nonparametric measure of noise in x-ray diagnostic images-mammography.

Objective.In x-ray diagnostics, modern image reconstruction or image processing methods may render established methods of image quality assessment inadequate. Task specific quality assessment by using model observers has the disadvantage of being very labour-intensive. Therefore, it appears highly desirable to develop novel image quality parameters that neither rely on the linearity and the shift-invariace of the imaging system nor require the acquisition of hundreds of images as is necessary for the application of model observers, and which can be derived directly from diagnostic images.Approach.A new measure for the noise based on non-maximum-suppression images is defined and its properties are explored using simulated images before it is applied to an exposure series of mammograms of a homogeneous phantom and a 3D-printed breast phantom to demonstrate its usefulness under realistic conditions.Main results.The new noise parameter cannot only be derived from images with a homogeneous background but it can be extracted directly from images containing anatomic structures and is proportional to the standard deviation of the noise. At present, the applicability is restricted to mammography, which satisfies the assumption of short covariance length of the noise.Significance.The new measure of the noise is but a first step of the development of a set of parameters that are required to quantify image quality directly from diagnostic images without relying on the assumption of a linear, shift-invariant system, e.g. by providing measures of sharpness, contrast and structural complexity, in addition to the noise measure. For mammography, a convenient method is now available to quantify noise in processed diagnostic images.

The regression detectability index RDI for mammography images of breast phantoms with calcification-like objects and anatomical background.

Currently, quality assurance measurements in mammography are performed on unprocessed images. For diagnosis, however, radiologists are provided with processed images. This image processing is optimised for images of human anatomy and therefore does not always perform satisfactorily with technical phantoms. To overcome this problem, it may be possible to use anthropomorphic phantoms reflecting the anatomic structure of the human breast in place of technical phantoms when carrying out task-specific quality assessment using model observers. However, the use of model observers is hampered by the fact that a large number of images needs to be acquired. A recently published novel observer called the regression detectability index (RDI) needs significantly fewer images, but requires the background of the images to be flat. Therefore, to be able to apply the RDI to images of anthropomorphic phantoms, the anatomic background needs to be removed. For this, a procedure in which the anatomical structures are fitted by thin plate spline (TPS) interpolation has been developed. When the object to be detected is small, such as a calcification-like lesion, it is shown that the anatomic background can be removed successfully by subtracting the TPS interpolation, which makes the background-free image accessible to the RDI. We have compared the detectability obtained by the RDI with TPS background subtraction to results of the channelized Hotelling observer (CHO) and human observers. With the RDI, results for the detectabilityd'can be obtained using 75% fewer images compared to the CHO, while the same uncertainty ofd'is achieved. Furthermore, the correlation ofd'(RDI) with the results of human observers is at least as good as that ofd'(CHO) with human observers.

The thyroid axis 'setpoints' are significantly altered after long-term suppressive LT4 therapy.

The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All patients had at least one known TSH-level≥0.01 mU/l (lower detection limit) and <1.0 mU/l within 2 years of initial treatment (time 1) and had at least one TSH-value≥0.01 mU/l and <1.0 mU/l after continuous LT4 therapy for a minimum of 5 years (time 2).At time 2 the mean LT4 dosage/kg body weight, TSH, FT3, and FT4 levels were significantly lower than at time 1, while body weight was higher. At time 2, the FT3/FT4 ratio rate had dropped significantly (p<0.001). At time 1, patients would require 2.96 µg/kg body weight to reach total TSH suppression. The dose of levothyroxine/kg required for suppression can be lowered by about 0.05 µg/kg body weight for each year of suppressive therapy. After a median of 12.7 years of continuous suppressive levothyroxine therapy, patients would require 2.25 µg/kg body weight (-23.5%) to reach total TSH-suppression. At least part of this reduction was independent of aging. As a result of changes in thyroid hormone metabolism and thyroid axis setpoint, long-term TSH-suppressive therapy contributes to a reduction in the dosage of levothyroxine per kilogram body weight required for full TSH suppression over time.

[Changes in therapy for breast cancer patients as a result of mammography screening. An analysis of Bavarian cancer registry data from 2000 to 2008]. / Veränderungen der Therapie des Mammakarzinoms in Bayern seit Einführung des Mammografie-Screenings. Eine Analyse bayerischer Krebsregisterdaten der Jahre 2000 bis 2008.

PURPOSE: A quality controlled mammography screening programme was initiated at the end of 2003 in Bavaria, a region with 12.5 million inhabitants, and transferred over to the national screening programme at the end of 2006. The purpose of this study was to evaluate immediate population-based consequences of mammography screening on breast cancer therapy. METHODS: Data from 75 475 breast cancer cases, diagnosed between 2000 and 2008 and registered in one of the 6 Bavarian clinical cancer registries were analysed. 51.4% of these patients were between 50 and 69 years of age and therefore the target population for screening. Trends of prognostic factors and standard therapies were calculated for 3 age groups (≤49 years, 50-69 years, ≥70 years) by means of annual percentages as well as 95%-confidence intervals for the percent difference between 2000 and 2008 (year of diagnosis). For interpretation of therapy trends, logistic regression models were calculated. RESULTS: Therapy trends showed that the increasingly favourable stage distribution may have resulted in the reduction of more radical surgical methods such as mastectomy (2000: 32.6%; 2008: 19.6%) or axillary dissection (89.0% vs. 37.0%), especially for women aged 50-69. An increase of radiation therapies (59.7% vs. 66.6%) can be explained to some extent by the increase in breast conserving surgeries. The shift to more favourable prognostic factors led, in accordance with the guidelines, to an increase of the proportion of singular endocrine therapies (28.5% vs. 40.7%), a decrease of chemotherapies (20.4% vs. 13.1%) and therefore to more gentle systemic therapies overall. These trends strengthened in the years following the introduction of screening, with a simultaneous rise of screening participants in the target population. CONCLUSION: The introduction of mammography screening in Bavaria has already shown the expected trend towards more favourable prognostic factors. Among other things, this could be a reason for the increasing use of more gentle therapies. Whether the screening in Bavaria leads to a mortality reduction, has to be analysed on the basis of an initial comparison of participation status followed by the trends in mortality thereafter.

The Swiss Army physical fitness test battery predicts risk of overuse injuries among recruits.

AIM: The aim of this study was to quantify the discriminative power of physical performance tests to recognize conscripts with enhanced risk of acute and overuse injuries in specific, physically demanding occupational specialties of the Swiss Army. The five performance tests investigated represent the Swiss Army Physical Fitness Test Battery. METHODS: Physical fitness performances were assessed during recruitment procedures prior to military service, and injury occurrences were assessed during 18 weeks of boot camp. Complete fitness and injury data of 459 volunteers from four military occupational specialties were collected. Discriminative power of volunteers' aerobic endurance capacity, trunk muscle fitness, muscle power of upper and lower extremities, and balance for predicting risk of acute injuries and for predicting risk of overuse injuries was calculated using receiver operating characteristic curve analysis. RESULTS: The presented fitness tests had no discriminative power for predicting the risk of acute injuries. However, the trunk muscle fitness test was discriminative in predicting overuse injuries in all four military occupational specialties, progressive endurance run in three, balance test in two, and standing long jump in one. Only the seated shot put had no significant power for predicting overuse injuries in all four study groups. However, for different occupational specialties, different fitness parameters were discriminative to predict overuse injuries. CONCLUSION: It is possible to conclude that the fitness tests used allow detection of conscripts with enhanced overuse injury risk in physically demanding occupational specialties and therefore provide an indicator to select suitable personnel for physically demanding jobs in a military organization.

Ambulatory physical activity in Swiss Army recruits.

The aim of this study was to objectively assess and compare the type, duration and intensity of physical activity during the basic training provided by each of 5 selected Swiss Army occupational specialties. The first objective was to develop and validate a method to assess distance covered on foot. The second objective was to describe and compare physical activity levels among occupational specialties. In the first part of the study, 30 male volunteers completed 6 laps of 290 m at different gait velocities. Data from 15 volunteers were used to develop linear regression equations for the relationship between step frequency and gait velocity, and data from the other 15 volunteers were used to verify the accuracy of these equations. In the second part of the study, 250 volunteers from 5 military schools (each training school for a different occupational specialty) wore heart-rate, acceleration and step-count monitors during workdays of weeks 2, 4, 8 and 10 of their basic training. Sensor data were used to identify physically demanding activities, estimate energy expenditure (based on already published algorithms) and estimate distance covered on foot (based on the algorithm developed in the first part of this study). A branched model using 2 regression equations (gait velocity=0.705∙step frequency for walking speeds below 1 m/s and gait velocity=1.675∙step frequency - 1.464 for faster gait velocities) was shown to be accurate for estimating distance covered on foot. In the training schools investigated, average physical activity energy expenditure was 10.5 ± 2.4 MJ per day, and trainees covered 12.9 ± 3.3 km per day on foot. Recruits spent 61.0 ± 23.3 min per day marching and 33.1 ± 19.5 min per day performing physically demanding materials-handling activities. Average physical activity energy expenditure decreased significantly from week 2 to week 8. The measurement system utilised in the present study yielded data comparable to those of prior studies that applied alternative methods. Nevertheless, the new sensor-based, objective measurement system used provided more information on daily physical activity and demands than traditional, single measurement instruments. The average daily total energy expenditure values in all training schools investigated were within the range found for the armed forces of other nations and for professional athletes.

Recognition of activities in children by two uniaxial accelerometers in free-living conditions.

The aim of this study was to develop a classification procedure for accelerometer data to recognize the mode of children's physical activity (PA) in free-living conditions and to compare it with an established cutoff method. Hip and wrist accelerometer data with an epoch interval of 1 s were collected for 7 days from 24 girls (age: 10.7 ± 1.7 years) and 17 boys (age: 10.6 ± 1.6 years). Videos were recorded during the same 7 days at several points of time at school and during leisure time. Each second of video data was labeled as one of nine activity classes. A classification procedure based on pattern recognition algorithms was trained with the accelerometer data relating to respective video labels of half of the children and tested against the data from the other half of the children. The overall recognition rate of the classification procedure was 67%. The procedure was able to classify 90% of stationary activities, 83% of walking, 81% of running and 61% of jumping activities. The remaining activities could not be recognized by the main classifier. This study developed a classification procedure based on well-accepted accelerometers and video recordings to recognize children's PA in free-living conditions. It has been shown to be valid for the activities of being stationary, walking, running and jumping. In contrast to former measurement and analysis procedures, this method is able to determine the modes of specific activities among children. Consequently, the presented classification procedure provides additional information on the PA behavior in children registered by established accelerometers.

[Ten years of epidemiological cancer registration in Bavaria]. / Zehn Jahre Krebsregistrierung in Bayern.

For a large territorial state like Bavaria only a decentralised cancer registration structure promises successful results: in the form of regional clinical cancer registries and--using the clinical registration as a base--one population-based registry. After ten years of epidemiological cancer registration in Bavaria it can now be shown that the chosen registration concept has proved itself. Currently the completeness of cancer notifications exceeded the international recommended threshold of 90%. A largely complete data stock is available for the years of diagnosis from 2004 to 2005. The task sharing between clinical and population-based cancer registries avoids double registration of data. Both types of registries are supporting physicians and hospitals with a wide palette of services. Together they enable transparency of cancer occurrence as well as transparency of health care for tumour patients.

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma.

Deletions in the short arm of chromosome 17 (17p) involving the tumor suppressor TP53 occur in up to 20% of diffuse large B-cell lymphomas (DLBCLs). Although inactivation of both alleles of a tumor suppressor gene is usually required for tumor development, the overlap between TP53 deletions and mutations is poorly understood in DLBCLs, suggesting the possible existence of additional tumor suppressor genes in 17p. Using a bacterial artificial chromosome (BAC) and Phage 1 artificial chromosome (PAC) contig, we here define a minimally deleted region in DLBCLs encompassing approximately 0.8 MB telomeric to the TP53 locus. This genomic region harbors the tumor suppressor Hypermethylated in Cancer 1 (HIC1). Methylation-specific PCR demonstrated hypermethylation of HIC1 exon 1a in a substantial subset of DLBCLs, which is accompanied by simultaneous HIC1 deletion of the second allele in 90% of cases. In contrast, HIC1 inactivation by hypermethylation was rarely encountered in DLBCLs without concomitant loss of the second allele. DLBCL patients with complete inactivation of both HIC1 and TP53 may be characterized by an even inferior clinical course than patients with inactivation of TP53 alone, suggesting a functional cooperation between these two proteins. These findings strongly imply HIC1 as a novel tumor suppressor in a subset of DLBCLs.

Intra- and interobserver variability of thyroid volume measurements in healthy adults by 2D versus 3D ultrasound.

UNLABELLED: Thyroid volume measurement by ultrasonography (US) is essential in numerous clinical diagnostic and therapeutic fields. While known to be limited, the accuracy and precision of two-dimensional (2D) US thyroid volume measurement have not been thoroughly characterized. OBJECTIVE: We sought to assess the intra- and interobserver variability, accuracy and precision of thyroid volume determination by conventional 2D US in healthy adults using reference volumes determined by three-dimensional (3D) US. Design, METHODS: In a prospective blinded trial, thyroid volumes of ten volunteers were determined repeatedly by nine experienced sonographers using conventional 2D US (ellipsoid model). The values obtained were statistically compared to the so-called true volumes determined by 3D US (multiplanar approximation), the so-called gold standard, to estimate systematic errors and relative deviations of individual observers. RESULTS: The standard error of measurement (SEM) for one observer and successive measurements (intraobserver variability), was 14%, and for different observers and repeated measurements (interobserver variability), 17%. The minimum relative thyroid volume change significantly different at the 95% level was 39% for the same observer and 46% for different observers. Regarding accuracy, the mean value of the differences showed a significant thyroid volume overestimation (17%, p < 0.01) by 2D relative to 3D US. CONCLUSION: 2D US is appropriate for routine thyroid volumetry. Nevertheless, the so-called human factor (random error) should be kept in mind and correction is needed for methodical bias (systematic error). Further efforts are required to improve the accuracy and precision of 2D US thyroid volumetry by optimizing the underlying geometrical modeling or by the application of 3D US.

Cold induction of the Bacillus subtilis bkd operon is mediated by increased mRNA stability.

Recently it has been demonstrated that the ptb - bcd - buk - lpdV - bkdAA - bkdAB - bkdB operon ( bkdoperon) of Bacillus subtilis, which encodes the enzymes that catalyze the degradation of branched-chain amino acids, is inducible by a temperature downshift from 37 to 18 degrees C. Deamination and oxidative decarboxylation of isoleucine generates 2-methyl-butyryl-CoA, which serves as the precursor of anteiso-branched fatty acid species. Most probably, the induction of this operon upon cold shock ensures an increase in the content of anteiso-branched fatty acids in the membrane lipids at low temperature, thus permitting maintenance of membrane fluidity at lower temperatures. In the present study, we have analyzed the mechanism of cold induction of the bkd operon and of four further cold-inducible transcriptional units in B. subtilis. We demonstrate that cold induction of these genes is mediated by an increase in the stability of the corresponding mRNAs. None of the promoters that control the five transcriptional units analyzed is actually cold-inducible. Furthermore, the results of this study indicate that the 5' leader regions are not involved in the cold-induced stabilization of the mRNAs. The structural elements that enhance mRNA stability must therefore be restricted to the 3'-ends and/or the coding regions.

Bacillus subtilis functional genomics: genome-wide analysis of the DegS-DegU regulon by transcriptomics and proteomics.

The DegS-DegU two-component regulatory system of Bacillus subtilis controls various processes that characterize the transition from the exponential to the stationary growth phase, including the induction of extracellular degradative enzymes, expression of late competence genes and down-regulation of the sigma(D) regulon. The degU32(Hy) mutation stabilizes the phosphorylated form of DegU (DegU-P), resulting in overproduction of several extracellular degradative enzymes. In this study, the pleiotropic DegS-DegU regulon was characterized by combining proteomic and transcriptomic approaches. A comparative analysis of wild-type B. subtilis and the degU32(Hy) mutant grown in complex medium was performed during the exponential and in the stationary growth phase. Besides genes already known to be under the control of DegU-P, novel putative members of this regulon were identified. Although the degU32(Hy) mutant is assumed to contain high levels of phosphorylated DegU in the exponential as well as in the stationary growth phase, many genes known to be positively regulated by DegU-P did not show enhanced expression in the mutant strain during exponential growth. This is consistent with the fact that most genes belonging to the DegS-DegU regulon are subject to multiple regulation; this is also reflected in the strong stationary-phase induction of these genes in the mutant strain. As expected, during the exponential growth phase, the sigma(D) regulon was expressed at significantly lower levels in the degU32(Hy) mutant than in the wild type.

[Incidence and spectrum of malignant disease among dialysis patients in North Bavaria]. / Inzidenz und Spektrum maligner Erkrankungen bei Dialysepatienten in Nordbayern.

BACKGROUND AND OBJECTIVE: In end-stage renal failure the incidence of cancer is increased. With regard to frequency and pattern of distribution of the tumors, there are substantial regional differences. Since this topic has to date received only minimal attention in Germany, we undertook a multi-centric analysis (8 dialysis centres) in North Bavaria in order to address the occurrence of malignant diseases in end-stage renal failure. PATIENTS AND METHODS: Of a total of 2228 patients, who underwent hemodialysis in the period from 1990 - 99 as a consequence of end-stage renal failure, the medical records of 1727 persons were analysed. Only those patients were considered, whose malignancy was diagnosed in the course of the dialysis. The Saarland cancer register served as a comparative age- and sex-matched population, with which we calculated the expected frequency of the various cancers as well as the standard incidence ratio (SIR) for the dialysis patients. RESULTS: In total 125 malignant diseases were documented. The cancer incidence was highest in the first year of treatment and was clearly lower in the subsequent periods. Of great importance was the age of the patients. The highest SIR scores were found for patients of middle age (35 - 50 years). An enhanced risk for cancer of the kidney, bladder, prostate, liver, oral cavity and the pharynx and larynx, as well as of the lymphatic and hemopoetic systems was found, while there was no or only a slight increase in the frequency of carcinoma of the mammary gland, stomach, colon-sigma-rectum and bronchial systems. CONCLUSION: The high incidence of cancer in end-stage renal failure should be given greater attention. Particularly in the high-risk group of younger dialysis patients, a regular screening - especially for tumors of the kidney, bladder and liver - appears justified.

A comprehensive two-dimensional map of cytosolic proteins of Bacillus subtilis.

Proteomics relying on two-dimensional (2-D) gel electrophoresis of proteins followed by spot identification with mass spectrometry is an excellent experimental tool for physiological studies opening a new perspective for understanding overall cell physiology. This is the intriguing outcome of a method introduced by Klose and O'Farrell independently 25 years ago. Physiological proteomics requires a 2-D reference map on which most of the main proteins were identified. In this paper, we present such a reference map with more than 300 entries for Bacillus subtilis proteins with an isoelectric point (pI) between 4 and 7. The most abundant proteins of exponentially growing cells were compiled and shown to perform mainly housekeeping functions in glycolysis, tricarboxylic acid cycle (TCC), amino acid biosynthesis and translation as well as protein quality control. Furthermore, putative post-translational modifications were shown at a large scale, with 47 proteins in total forming more than one spot. In a few selected cases evidence for phosphorylation of these proteins is presented. The proteome analysis in the standard pI range was complemented by either stretching the most crowded regions in a narrow pH gradient 4.5-5.5, or by adding other fractions of the total B. subtilis proteome such as alkaline proteins as well as extracellular proteins. A big challenge for future studies is to provide an experimental protocol covering the fraction of intrinsic membrane proteins that almost totally escaped detection by the experimental procedure used in this study.

Influence of continuous and discontinuous training protocols on subcutaneous adipose tissue and plasma substrates.

It has been shown that bouts of high-intensity exercise may reduce subcutaneous adipose tissue more than low-intensity exercise. The aim of the present study was to examine if a discontinuous training protocol is more successful in reducing adipose tissue than a continuous endurance training protocol. Fourteen untrained male volunteers were divided into two groups and trained for 10 weeks performing 3 discontinuous or 3 continuous workouts weekly (discontinuous exercise: 25 times 80 s 35% VO2max and 40 s 80% VO2max; continuous exercise: 50 min 50% VO2max). The discontinuous and the continuous training resulted in a similar subcutaneous adipose tissue loss, determined by skinfold measurement, in the leg above the patella (-2.4+/-2.4 and -2.4+/-1.4mm, respectively). The normalised plasma concentrations of free fatty acid, glycerol, beta-hydroxybutyrate, and lactate were similar throughout the final exercise test at the end of the training period. Our data suggested that the discontinuous protocol, selected so that the average intensity was similar to that of the continuous protocol, was not better than the latter in reducing subcutaneous adipose tissue.

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg]. / Häufigkeit des familiären nicht-medullären Schilddrüsenkarzinoms im Krankengut der Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg.

AIM: In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. PATIENTS AND METHODS: In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. RESULTS: 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). CONCLUSION: A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

Differentiated thyroid cancer in children and adolescents.

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.