The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Health-related quality of life in paediatric patients with congenital heart defects: association with the type of heart defect and the surgical technique.

The aim of the study was to investigate the impact of a number of surgical interventions for a various congenital cardiac defects (CHDs) on self-reported HRQoL. METHODS: Patients who had received corrective surgery of several congenital heart defects (surgical VSD closure, Fallot, TGA after atrial or arterial switch or Fontan-type circulation for univentricular AV-connection) were interviewed in the office of their home peadiatric cardiologist. HRQoL in children along 7 dimensions was assessed using a standardised questionnaire (PEDQoL); information on the medical case history of each respondent was also collected. STATISTICS: HRQoL was assessed in the questionnaire by asking about the frequency (never, rarely, often, always) of specific negative experiences; more frequent experiences indicate a lower quality of life. Frequency expressions were transformed into numerical values (25, 50, 75, 100%), and mean values for HRQoL were calculated for each patient and for each domain. Differences in HRQoL among patients with different types of interventions were analysed using the Mann-Whitney Test or the Kruskal-Wallis Test as appropriate; p values <0.05 were considered to indicate significant differences, while p values <0.1 were considered to indicate notable trends. RESULTS: Patients: 169 patients (60% male, 40% female) were part of the study. The mean age was 11.6 years; 50 patients had surgical VSD closure, 52 surgeries for Tetralogy of Fallot (22 transannular patch, 18 no transannular patch, 12 inaccurate description), 40 had complete transposition of the great arteries (28 atrial switch, 12 arterial switch), 22 had a Fontan-type procedure for univentricular AV-connection. HRQoL differed little among patients with different CHDs for the items "relation to friends," "interactions in the affected families", and "own body image". For other items, notable differences emerged: patients with univentricular hearts rated their physical capacity worse and showed a tendency towards negative ratings in other domains. On the other hand, patients after Fallot or TGA correction tended to rate their HRQoL in several domains as relatively high. Focusing on the mode of surgery for Fallot repair, respectively, TGA correction the only significant difference was found for "physical capacity" in TGA (atrial vs. arterial repair). Mustard patients tended to rate most items worse. Physical capacity was rated worst by patients with a Fontan circulation. Repeated surgery led to lower ratings for all domains except "physical capacity" and "body image". CONCLUSIONS: Different surgical techniques for CHD do not affect children's and adolescents' self-reported HRQoL to the extent that one would expect. This observation is in line with observations in groups of children with different chronic diseases. Specialised psychosocial support is necessary in order to maintain this positive self-evaluation and to ensure patients are able to lead autonomous personal and professional lives.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

[Body measurements of children and adolescents in Germany. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Körpermasse bei Kindern und Jugendlichen in Deutschland. Ergebnisse des Kinder- und Jugendgesundheitssurveys (KiGGS).

In the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS), a number of anthropometric parameters were assessed in a standardised way in 17,641 boys and girls. To this end, body weight and height, head circumference and upper arm length, as well as two skinfold thicknesses (triceps, subscapular) were measured for the entire age range (0-12 years); starting from 6 years of age, elbow breadth and from 11 years of age waist and hip circumference were measured in addition. For all parameters, means with confidence intervals are reported per age (in years) and gender. Median graphs depict the changes with increasing age according to gender for each body measurement. The complex age-related anthropometric developments along with significant gender specificity show the full range of the dynamic physical development in boys and girls. Based on skinfold measurement data, the body fat percentage was estimated. Thickness and location of the skinfolds, as well as the calculated waist-to-hip ratio is used as an indicator for gender-specific fat distribution. Using the frame index, it is attempted to estimate skeletal robustness. For the anthropometric parameters studied, hardly any regional differences were found. However, head circumference, frame index and all parameters strongly associated with body fat show a significant social status gradient. Children and adolescents with migration background have on average a lower height, larger waist circumference and higher percentage of body fat.

[Sexual maturation of children and adolescents in Germany. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Sexuelle Reifung von Kindern und Jugendlichen in Deutschland. Ergebnisse des Kinder- und Jugendgesundheitssurveys (KiGGS).

Following the standstill in maturity acceleration in the eighties of the twentieth century, now a further shift in maturity development towards younger ages is the issue of an international and also German discussion. The collection of sexual maturity data in boys and girls as part of the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS) is intended to pro vide population-representative information on sexual maturation and to evaluate associations between maturity status and selected health and social data. Girls were interviewed regarding their first menstrual period (menarche) and boys regarding voice change (status-quo method). Pubic hair was self-assessed by children and adolescents from 10 to 17 years of age, based on drawings of Tanner's defined developmental stages. The median age for menarche, for voice change and pubic hair stages were calculated using a logit model. At an age of 10 years, 42.4 % of girls and 35.7 % of boys report the development of pubic hair. At 17 years of age, the majority of girls and boys have reached the stages PH5 (girls 57.5 %, boys 47.8 %) and PH6 (girls 23.6 %, boys 46.5 %) according to Tanner. The average age for each pubic hair stage is lower in girls (PH2 10.8; PH3 11.7; PH4 12.3; PH5 13.4 years) than in boys (PH2 10.9; PH3 12.6; PH4 13.4; PH5 14.1). The median age at menarche is 12.8 years, the median for voice change (voice low) 15.1 years. Significant differences in age at menarche are found in girls depending on socioeconomic status (12.7/12.9/13.0 years for low/middle/high status) and between girls with and without migration background (12.5/12.9 years). No differences in age at menarche can be seen between East and West Germany or cities and rural areas. The association between maturity status and BMI is more pronounced in girls than in boys. Overall, the onset of maturity development in German children and adolescents is not significantly earlier than in other European studies.

[Injuries among children and adolescents (1-17 years) and implementation of safety measures. Results of the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Verletzungen bei Kindern und Jugendlichen (1-17 Jahre) und Umsetzung von persönlichen Schutzmassnahmen. Ergebnisse des bundesweiten Kinder- und Jugendgesundheitssurveys (KiGGS).

Parent interviews with regard to their children's accidents and to accident protective measures in the Health Interview and Examination Survey for Children and Adolescents (KiGGS) aimed at extending our knowledge of age- and gender-specific injuries and to identify risk groups and risk factors for injury prevention. The parents of 16,706 children (aged 1-17 years) were asked about their children's injuries within the last 12 months which were medically treated, and about accident mechanisms, consequences of injuries, and ambulatory and hospital treatment. In addition, parents and children aged 11 to 17 years (n = 6813) were asked to give information on protective measures. According to the parents 15.9 % of the children had at least one injury within the last 12 months, 15.2 % because of an accident and 0.8 % because of assault. In the age group 1-17 boys have been injured significantly more often than girls (17.9 % vs. 14,0 %). Overall, 13.3 % of 2,410 injured children and adolescents were hospitalized. Two thirds of the accidents among toddlers were domestic accidents (60 %) whereas leisure and sport accidents were most prevalent in children and adolescents aged 5-14 years and 15-17 years (32.1 % and 38.9 %). The proportion of accidents in child care facilities and educational institutions tripled from infancy to school age (age 5-14 years) (10.9-28.7 %), as did traffic accidents (5.6-16.7 %). The three most frequent injury mechanisms in the age range 1-17 years were falls on level ground (35.2 %), falls from heights (25.2 %) and collisions with objects or persons (20.6 %). Falls from heights showed the highest risk in toddlers (35.8 %). Contusions, sprains and strains increased to a highest level of 50.9 % in adolescents; likewise, bone fractures increased from 10.7 % in toddlers to 21.8 % in adolescents aged 15-17 years. An influence of socioeconomic status on injuries overall and on consequences of injuries was not seen. For traffic accidents in children aged 1-17 years boys (p = 0.019) and girls (p = 0.047) from families with lower socioeconomic status showed higher rates of accidents than children from families with higher socioeconomic status. The application of protective measures was lowest in the age group 14-17 years. While according to the parents about 90 % of children aged 3-4 years wear a helmet when riding a bicycle or when skating, this quote was lower in the age group 5-14 (60 %) and dropped to about 15 % in the age group 14-17 (about 15 %). Also the rate for using protective clothes was lowest in age group 14-17 (boys 41.8 %; girls 52.2 %). In children and adolescents the rate of self-reported helmet use is lower than estimated by their parents. In all age groups migration background and low socioeconomic status were associated with lower use of protective measures (helmets and protective clothes). The age related data analysis should be the starting point in prevention measures for specific risk groups considering migration and socioeconomic status. Prevention activities in traffic should focus on families with low social status. Adolescents should be specifically and adequately addressed regarding the benefits of certain safety measures when riding a bicycle and when skating.

[Biochemical measures in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Biochemische Messparameter im Kinder- und Jugendgesundheitssurvey (KiGGS).

In the framework of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) a variety of biochemical parameters was determined in order to provide objective information on health status and particular health risks, in addition to parent interview data and anthropometric measurements. Overall 43 parameters covered three areas of particular public health interest: micronutrient deficiency, seroepidemiology of infectious diseases and immunization status, and risk indicators or risk factors for chronic non-communicable diseases. A review of available evidence regarding valid reference or cutoff values as well as the standardization of laboratory methods led to the categorization of these parameters into five classification categories. Here, we discuss the present first descriptive results on selected parameters representing the various categories. In order to determine the public health impact of measurement results, and perhaps even derive normative reference data relevant to health care, more detailed analyses will be required. In the first step, these will focus on cross-sectional analyses of the association between biochemical parameters and other health-related anthropometric and sociodemographic variables. Intermediate and long-term objectives will include the construction of multidimensional reference values taking into account several laborato ry data and other clinical information at the same time, and the prognostic validation of reference or cut-off values based on a follow- up of the study participants for clinical outcomes.

[Motor Fitness. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Motorische Leistungsfähigkeit. Ergebnisse des Kinder- und Jugendgesundheitssurveys (KiGGS).

Motor fitness was investigated in children and adolescents aged 4-17 using specific short tests. These tested the motor abilities: co-ordination, strength, cardiorespiratory fitness and flexibility. Among the 4-10 year olds, the focus of the investigation was on recording coordination, strength and flexibility; in the age group of the 11-17 year olds it was on recording cardiorespiratory fitness. The current investigation describes motor fitness based on the tested abilities according to age, sex and sociodemographic aspects. In all the test tasks, as expected, there are better results from older children and adolescents than from younger ones. Among the 4-10 year olds, girls display a slightly higher motor fitness in five out of the six tasks. In cardiorespiratory fitness, the cycle ergometer test for the 11-17 year olds shows better results for boys. The results indicate that there is a correlation between migrant status, social status and motor fitness. The shown differences point out that possible intervention programmes should be specifically attuned to age and sex as well as to the concerns of children and families with a migrant background and those of low social status. These collected data on motor fitness produced a database, representative of Germany. This will enable statements on state and development of motor fitness in children and adolescents in the future.

[The National Child and Adolescent Health Survey. The complete concept]. / Der bundesweite Kinder- und Jugendgesundheitssurvey. Das Gesamtkonzept.

The German National Health Interview and Examination Survey for Children and Adolescents aims at obtaining generalisable and practically convertible data and knowledge of the health situation of children and adolescents aged between 0 and 18 and living in Germany. After an extensive preparatory period of conceptional work by the Robert Koch Institute the beginning of this study is planned for spring 2003. Over a period of three years a representative sample of 18,000 young people will be medically examined and will be interviewed together with their parents. The investigational programme of the survey consists of a central part encompassing questionnaires and medical analyses of the most important health topics in childhood and adolescence. In addition, complementary modules will analyse subpopulations in-depth and extensively for specific aspects and questions. These modules are usually developed and financed by cooperating partners of the Robert Koch Institute. Soon after completion of the survey data first results will be made freely available to the scientific community in Public Use Files. These Files will become relevant sources for future health reporting addressing children and adolescents. Furthermore, they represent a reliable data base for epidemiological research and prevention programmes.

[The physical examination within the scope of The Child and Adolescent Health Survey]. / Die körperliche Untersuchung im Rahmen des Kinder- und Jugendgesundheitssurveys.

The National Health Survey for Children and Adolescents intends a comprehensive description of the health status of children and adolescents. In this context physical examination of children and adolescents permits collection of objective data concerning physical development, certain body functions and selected performance parameters. Most important are indicators pointing towards increasing developmental and health problems in children and adolescents, which are partly predictive for the health status as an adult. Body measurements including stages of puberty will be taken, the blood pressure measured, vision tests carried out, coordination skills and endurance tested. Besides, if acute symptoms are detected, severity of atopic dermatitis is recorded. The methods and instruments have been tested in a pilot study over a period of one year and were optimised for the main study.

[The motor activity study segment as pilot study of The Child and Adolescent Health Survey]. / Der Untersuchungsteil Motorik im Pretest des Kinder- und Jugendgesundheitssurveys.

In the Health Survey for Children and Adolescents the examination of motor activity is one aspect of physical health covered by the study. This underlines the importance of physical activity for physical development in early years. This first representative child and adolescent study for Germany intends to obtain data on motor activity and to allow for the implementation of specific intervention programmes encouraging physical activity. The specific general conditions under which the survey is conducted restrict the selection and scope of possible instruments to a minimal programme, including fitness tests, strength in combination with endurance and coordinative skills as well as flexibility. In a pilot study the suitability, feasibility and the obtained evidence of selected single motor tests were tested. This article explains the choice of instruments and methods used in the examination of physical fitness. It also discusses methodological difficulties which affect the standardisation of tests and the requirements regarding personnel. A major concern of the pilot study was the evaluation of tested instruments with regard to gender and age differences. For the main survey the following tests are recommended: coordination (balancing backwards, one-leg-footing, sideway jumping), perseverance (sit-ups, push-ups), and flexibility (trunk bending).

Influence of muscarinic ligands on the amplitudes of the evoked surface potential's late components in the optic tectum of the urodele Plethodon jordani.

Recordings of field potentials from the tectal surface of an urodele amphibian were obtained in an in vitro preparation under influence of various muscarinic drugs. Bath applied acetylcholine (ACh) led to no change in the amplitudes or the shape of the evoked potentials. If the ACh-esterase blocker (-)-physostigmine was applied synchronously, the late components of the surface potential increased in amplitude. The non-selective cholinergic agonist carbachol showed a similar effect which was partially diminished by the nicotinic antagonist d-tubocurarine chloride (d-TC) and the muscarinic antagonist atropine sulfate. The application of the non-selective muscarinic agonist (+)-pilocarpine hydrochloride led to an increase of the late oligo- and polysynaptic events. This effect was reduced by the M(1)-antagonist pirenzepine dihydrochloride. The presented findings suggest that muscarinic receptors play a more important role in tectal processing than assumed in previous studies which emphasized the role of nicotinic receptors.

[Utilization of health screening studies and measures for health promotion]. / Inanspruchnahme von Früherkennungsuntersuchungen und Massnahmen zur Gesundheitsförderung.

Health-conscious behaviour of a population may be measured by the utilization rate in screening programs and health promotion measures. In the German National Health Interview and Examination Survey 1998, 7124 respondents were asked for their individual participation. The utilization in free health check-ups (1997) was 26.7% for men and 24.5% for women. Health related medical advice was given to 70.9% of men and 67.8% of women in the wake of the check-up. Annual early cancer screening test were taken by 22.6% of men and 36.5% of women. Cancer-related medical advice was reported by 42.4% of men and 43% of women. 10.5% of all respondents participate in health promotion measures, women two times more often than men (13.8% vs. 7%). The ranking according to the type of measures is: 44% for back (muscle) training, followed by nutrition consultation (13%), weight reduction (10%) and anti-smoking, -drinking and -substance use measures (4%). The results show differences in utilization rates for early cancer diagnosis, health checkups and health promotion programmes according to age, region, social status and health insurance type.

Connectivity of the salamander pretectum: an in-vitro (whole-brain) intracellular tracing study.

The amphibian optic tectum and pretectum have been analyzed in detail anatomically and physiologically, and a specific model for tecto-pretectal interaction in the context of the visual guidance of behavior has been proposed. However, anatomical evidence for this model, particularly the precise pattern of pretectotectal connectivity, is lacking. Therefore, we stained pretectal neurons intracellularly in an in-vitro preparation of the salamanders Plethodon jordani and Hydromantes genei. Our results demonstrate that the projections of neurons of the nucleus praetectalis profundus are divergent and widespread. Individual neurons may project divergently to telencephalic (ipsilateral amygdala and striatum), diencephalic (ipsi-and contralateral thalamus, contralateral pretectum), and mesencephalic (ipsi- and contralateral tectum and tegmentum) centers, and to the ipsi- and contralateral medulla oblongata and rostral spinal cord. The projection of pretectal cells to the optic tectum is bilateral; axonal structures do not show discernible patterns and are present in all layers of the superficial white matter. A classification of pretectal neurons on the basis of axonal termination pattern or dendritic arborization has not been possible. Our results do not support the hypothesis that a distinct class of pretectal neurons projects to a particular subset of tectal cells. Rather, the pretectum appears to influence the tectum indirectly, acting either on retinal afferents or modulating inhibitory interneurons.

Air pollution and mortality in East Berlin during the winters of 1981-1989.

BACKGROUND: The relationship between air pollution and mortality in East Berlin was examined for the winters of 1981-1989. METHODS: Regression analysis included daily mean levels of sulphur dioxide (SO2) and suspended particulates (SP), and was controlled for temperature, humidity, week-day, month, and year. Moving averages of previous pollution were also used. RESULTS: Each pollutant was a significant contributor to excess mortality. The strongest association was found for mortality lagged for 2 days, which depended significantly on the level of SP (beta for in SP = 0.876; P = 0.008) and SO2 (beta for in SO2 = 0.635; P = 0.012), when regressed separately. When omitting days with pollutant concentrations above 150 micrograms m-3, the pollutant-mortality relationship was linear, and a 100 micrograms m-3 increase was associated with a 6.1% (SP) and 4.5% (SO2) mortality increase 2 days later, when pollutants were considered separately; this was reduced to 4.6% (SP) and 2.8% (SO2) increase, when both were considered simultaneously. CONCLUSIONS: The results show that short-term associations between air pollutants and mortality in East Berlin did exist during the winters 1981-1989. Since the coefficients for SP and SO2 dropped when controlling for the other pollutant species, a similar strength of association with mortality for both pollutants was found.

[New aspects of assessment of physical development of children and adolescents by preventive examinations]. / Neue Aspekte der Beurteilung körperlicher Entwicklung von Kindern und Jugendlichen bei Vorsorgeuntersuchungen.

The results of the examinations of a representative cross-section were used as the basis for bringing up to date the standard values and ranges of variability of the body measurements of newborns according to gestational age, of head circumference up to the 3rd year and of body height and weight from 0-18 years. Tables and somatograms were also drawn up for the evaluation of body weight in relation to specific types of build, and standard values for skinfold thickness and total body fat were worked out in order to permit a biologically meaningful assessment of the physical development and nutritional status of children and adolescents. Alongside the description of the individual stages in the development of selected characteristics of maturation used in assessing sexual maturity, percentiles for the average age on reaching each of these stages of development will be available, together with a new series of photographs of breast, pubes and genital development.

Purification of monoclonal antibodies against the low-density lipoprotein receptor by preparative isotachophoresis.

A preparative free-flow isotachophoretic method for the purification of monoclonal antibodies from mouse ascites fluid and tissue culture media is described. This high-resolution method allows the direct separation of monoclonal antibodies from antibody-containing tissue culture media or ascites fluid and gives a better separation from the major contaminant protein fractions and a higher recovery of the monoclonal antibodies than anion-exchange chromatography. The purification can run continuously and without any time-consuming regeneration procedures; the monoclonal antibody is obtained under mild conditions in a small electrolyte volume.

[Colorectal carcinoma--intracavitary sonography]. / Intrakavitäre Sonographie.

Staging of rectal carcinoma effected in 32 patients via ultrasound was re-examined on the basis of histological findings. One patient was classified in T3 by ultrasound, although histologically he belonged to the T2 stage. In no case was the spread of the tumour underestimated. Other indications for endosonography of the rectum are: aftercare of patients subjected to deep resection, and diagnosis of extraluminal processes.