[Current therapy of polyarticular forms of juvenile idiopathic arthritis]. / Aktuelle Therapie der polyartikulären Verlaufsform der juvenilen idiopathischen Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA.

[Prediction of prognosis of pancreatic cancer based on the homing area]. / Voraussage der Prognose des Pankreaskarzinoms in seinem Homing-Areal.

The homing area is a genetically defined location where primary malignancy originates and local recurrences occur. In order to be completely successful, curative resections of malignant tumors have to eradicate the homing area. This is possible in colon resection where the borders of the homing area are distant from the tumor and the lymph nodes can easily be resected to remove possible node metastases. In contrast, the homing area of the pancreas comprises only the gland itself, similar to all other glandular organs. The high specificity of the homing area is demonstrated by the finding that even pancreatic islets are spared by the malignant disease. During fetal development the pancreas loses most of the original dorsal and ventral mesentery. Via short lymphatic pathways, metastatic cells leave the gland in a centrifugal manner and find their way to regional lymph nodes that often share drainage with other neighboring organs. The lymph nodes are arranged in multiple layers and not in flat mesentery-like structures. Radical resections are therefore difficult to achieve.

[PET-CT studies of metastasizing cancer of the colon and rectum. Variability of tumor aggressiveness as a micro-evolutionary process of cancer stem cells with predetermined prognosis]. / PET-CT-Untersuchungen zur Stammzellkarzinogenese im Kolorektalbereich. Malignitätsvariabilität als mikroevolutionärer Prozess mit festgelegter Prognose.

Formation of cancer stem cells which are both rare and variably therapy-resistant marks the beginning of a new disease without precursors. Based on molecular changes, these cells are derived from normal cells and exhibit pre-programmed malignant behaviour. In vitro studies have shown that hybrid cancers which behave in a similar way to Dukes A, B or C cancers in vivo can be produce by horizontal gene transfer. The level of aggressiveness follows a Galton curve in the probability distribution. In the current paper we analyzed colorectal cancers by PET-CT in follow-up studies which extended over several years. We conclude that the primary tumors behave differently from distant metastases. Radical exstirpation of the primary tumor is able to cure the malignant process if the homing area is resected. The primary tumor acts as the supplier of cancer stem cells for metastases which appear in different organs. When chemotherapy is administered the distribution of metastases in different organs appears dependent of the response or non-response of cancer stem cells to this therapy. Large numbers of colorectal carcinomas existed for the same time duration before death (15 years) independent of the malignancy grade. The tumor metastasizes immediately after formation. The primary tumor and the metastases appear variably quickly depending on the malignancy grade and are autonomic processes.

Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters.

Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P) are distinguished. We used voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA-C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and several cortical regions including insular cortex. Gray matter loss in the cerebellum and insular cortex was correlated with disease duration and severity. There was white matter loss in the brainstem, which was correlated with disease duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2 in cerebellum, pontine brainstem and cortical regions including insular cortex. In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina, and several cortical regions including insular cortex. A correlation with disease duration and severity was detected only for some small cortical areas. Direct comparison of MSA-C and MSA-P showed differences only in infratentorial brain regions where structural abnormalities were more pronounced in MSA-C than in MSA-P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem.

[Lymph vascularity and lymph node metastases on PET and PET-CT: immunohistological and clinical observations]. / Das Lymphgefässsystem (LGS I und II) aus chirurgischer Sicht. Lymphgefässe und Lymphknotenabsiedlungen, nach PET, PET-CT, immunhistologischen und klinischen Beobachtungen.

Sarcomatous malignancies only rarely develop regional lymph node metastases: about 2.7% of our evaluated cases. In this paper we provide evidence supporting a new hypothesis that two entirely separate lymph vascular systems exist in humans. One system (LGS I) exists in close proximity to the epithelium and drains into regional lymph nodes. Only sarcomas that originate in the epithelium or its immediate proximity are able to form regional lymph node metastases. The vast majority of sarcomatous malignancies (97.4% of cases) do not give rise to lymph node metastases, since they originate in proximity to a second, more deeply localized lymph node system (LGS II) in the mesenchymally derived tissues of the body. This second system has no connection to regional lymph nodes. Supporting evidence is provided by experience in the operative treatment of extremity lymphedema, PET-CT examinations, radionuclear lymphography, and scientific investigations using antibodies specifically directed at the elements of the lymph vascular system.

Intrasubject reproducibility of presurgical language lateralization and mapping using fMRI.

BACKGROUND: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. OBJECTIVE: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. METHODS: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). RESULTS: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. CONCLUSION: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

[PET examination of metastases of somatic carcinomas via the lymphatic system (thyroid gland and breast)]. / PET-Untersuchungen der Lymphwegmetastasierung somatischer Karzinome (Schilddrüse und Mamma). Ein Beitrag zur chirurgischen pathologischen Anatomie.

We previously showed that advanced visceral cancers (58 rectum cancers) are confined in their pattern of lymphatic spread to one caudocranial regional pathway and never appear in another one, even in cases of local recurrence. We have now investigated PET scan series of 94 somatic cancers (44 thyroid and 50 breast cancers). They too are confined in their pattern of lymphatic spread to paratracheal or ipsi-cervical or axillary pathways. Only when the main pathways are removed or blocked do they then force their way into mediastinal or collar regions. They never affect visceral regions.

Linking expert evaluations with public consultation to design water policy at the watershed level.

In view of the increasing demand for public participation in public affairs, the European Water Framework Directive requires public consultation when drawing up watershed management plans. Implementation of this Directive requires the development of methods for linking the scientific and technical knowledge of experts with the viewpoints expressed by local actors. The objective of this paper is to propose a public consultation method that can be used as early as the preliminary assessment of river basin characteristics, defined by the Directive, and at the scale of sub-watersheds that make up the district. A case study of a watershed in southern France illustrates this method.

Language mapping in less than 15 minutes: real-time functional MRI during routine clinical investigation.

Neurosurgical interventions often require the presurgical determination of language dominance or mapping of language areas. Results obtained by fMRI are closely correlated with invasive procedures such as electrical stimulation mapping or the intracarotid amobarbital test. However, language fMRI is not used routinely, because postprocessing is time-consuming. We utilized a real-time analysis software installed directly on the MR console computer and SPM99 as reference postprocessing software. We assessed the reliability of the immediate determination of language dominance based on individual activation maps by comparing the results of the visual analysis of images derived from conventional postprocessing with those produced by the real-time tool. All images were rated independently by six senior neurologists blinded to other data. We validated the robustness of the real-time method statistically by comparing global and regional lateralization indices derived from real-time and postprocessing analysis. Functional MRI was performed with a standard 1.5-T whole-body scanner. Brain activity was contrasted between an alternating semantic judgment and letter matching task. Twelve right-handed, healthy control subjects and 12 consecutive patients with drug-resistant, localization-related epilepsy were investigated. The semantic condition induced almost invariably left hemispheric activations in Broca's area, the premotor cortex, the dorsolateral prefrontal cortex, and the temporoparietal region. Although real-time analysis reduced noise less effectively than SPM99, visual ratings and lateralization indices produced highly concordant results with both methods. In conclusion, real-time fMRI, as used here, allowed reliable language lateralization and mapping in less than 15 min during routine clinical MRI investigation with no need for postprocessing.

[PET examinations of recurrent rectal carcinoma, 2]. / PET-Untersuchungen des rückfälligen Rectumcarcioms, Teil 2.

We have shown previously that the bodies of vertebrates are made of a somatic and a visceral component, separated by thin fascial sheets (Chirurg 66: 1230). We postulated that advanced visceral cancers are confined in their pattern of lymphatic spread to one or a few distinct metastatic pathways. In this they are fundamentally different from somatic cancers. To investigate this hypothesis in vivo, we evaluated positive lymph nodes (LNs) on PET scan series of 58 consecutive patients with rectum cancers (RC) compared to breast cancers (BC). We conclude that in RC, a visceral cancer spreads mostly along only one caudocranial pathway (regional, para-aortic, mediastinal, supraclavicular LNs) and never affects somatic LNs. In contrast, BC and urogenital carcinomas, as somatic cancers spread to regional somatic LNs, but do not affect visceral LNs.

[PET studies of recurrent rectal carcinoma. Fundamental aspects of lymphatic metastasis of visceral and somatic carcinomas]. / PET-Untersuchungen des rückfälligen Rectumcarcinoms. Gesetzmässigkeiten der Lymphmetastasierung visceraler und somatischer Carcinome.

We have shown previously that the bodies of vertebrates are made of a somatic and a visceral component, separated by thin fascial sheets (Chirurg 66: 1230). We postulated that advanced visceral cancers are confined in their pattern of lymphatic spread to one or a few distinct metastatic pathways. In this they are fundamentally different from somatic cancers. To investigate this hypothesis in vivo, we evaluated positive lymph nodes (LNs) on PET scan series of 58 consecutive patients with rectum cancers (RC) compared to breast cancers (BC). We conclude that in RC, a visceral cancer spreads mostly along only one caudocranial pathway (regional, para-aortic, mediastinal, supraclavicular LNs) and never affects somatic LNs. In contrast, BC and urogenital carcinomas, as somatic cancers spread to regional somatic LNs, but do not affect visceral LNs.

PET clínico en oncología / Clinical PET in Oncology

No disponible

[Inhibition of 18F-FDG uptake in glioblastoma cells by FDG and glucose]. / Hemmung der 18F-FDG-Aufnahme in Glioblastoma-Zellen durch FDG und Glucose.

It was the aim of the study to compare the inhibition of 18F-2-Fluor-D-deoxy-glucose uptake (18F-FDG) in tumor cells by various concentrations of FDG carrier or D-glucose in an experimental model using tissue culture and positron emission tomography (PET). Glioblastoma cells in culture were incubated with 18F-FDG with and without added carrier or in presence of glucose concentrations in the range from 0-5 mmol/L. Cellular uptake of 18F-FDG was measured after 20 min. of incubation in PBS-buffer containing different sugar concentrations. The uptake was determined with a PET camera. The similarity of the kinetics of the FDG and glucose uptake are backing the hypothesis that both substrates use the same carrier system. The more intense inhibition of the 18F-uptake by FDG can be explained by the different intracellular metabolism of both substrates. The results explain the clinical experience that there is an optimal 18F-FDG uptake in the patient's tumor when the blood glucose level is as low as possible and the specific activity of 18F-FDG is very high.

[Imaging of secondary pulmonary changes in central bronchial carcinomas by F-18-FDG PET]. / Darstellung sekundärer pulmonaler Veränderungen bei zentralen Bronchialkarzinomen in der F-18-FDG-PET.

AIM: The presented study was performed in order to evaluate the potential interference of secondary pulmonary changes (dystelectasis, retention pneumonia) with bronchial carcinomas in F-18-FDG-PET. METHOD: A retrospective analysis of F-18-FDG-findings in 33 patients with bronchial carcinoma (staging) was performed. Seven out of fourteen patients with central tumor localisation had secondary pulmonary changes (thorax-x-ray, CT), which were classified as dystelectasis or atelectasis in five cases and as retention pneumonia in two cases. RESULTS: Whereas dystelectasis and atelectasis without clinical signs of infection showed only mild to moderate FDG-accumulation (SUV 1.0-2.5; mean: 1.74), an intense FDG-uptake in the two cases with retention pneumonia (SUV 8.4 and 5.5) was observed. Despite of the typical wedge-like shape of pneumonia, differentiation between bronchial carcinoma and pneumonia can be a problem. CONCLUSION: We suggest, that an antibiotic treatment in patients with known retention pneumonia should be performed prior to the PET-scan in order to reduce the interference of inflammatory changes.

Functional imaging of Hodgkin's disease with FDG-PET and gallium-67.

We report a case of Hodgkin's lymphoma (Stage I B) which was studied using Ga-67-scintigraphy as well as whole body FDG-PET. Ga-67-scintigraphy detected a slightly increased uptake in the paraaortic and pelvic lymph nodes. However, FDG-PET was able to localize a much larger number of affected foci with a high glucose utilization rate in the right and left paraaortal regions, in the middle of the epigastrium, in the right and left parailiacal regions and one focus in the left upper mediastinum. Our experiences give rise to the assumption that FDG-PET ist significantly superior to gallium scintigraphy in Hodgkin's disease. Whole body FDG-PET can result in an upstaging of the patient and has therefore a major impact on the therapeutic management.

[Toxicity and radiation dosage of 2-(18F)-2-desoxy-D-glucose in positron emission tomography]. / Toxizität und Strahlendosis von 2-[18F]-2-Desoxy-D-Glukose in der Positronenemissionstomographie.

2-[18F]-FDG, a non-physiological glucose analogue, is the most important positron-emission- tomography (PET) radiopharmaceutical. As an example we refer to the production of 2-[18F]-FDG at the research center in Karlsruhe. 2-[18F]-FDG is synthesized in a "no carrier added" process. It is delivered at a maximal filling volume of 10 ml from a 14.5 ml batch with a batch-to-batch yield fluctuation from 5075 to 50,750 MBq and a specific activity from 1 to 10 GBq/mumol. The residual remaining synthesis reagents like solvents or catalysts have no toxicological relevance. The applicated dose per patient is in a range from 185 to 370 MBq and 1000 times lower than the correlating concentrations of stable FDG which can be regarded harmless in animals. 2-[18F]-FDG does not interfere with normal glucose metabolism. It is taken up by cells and phosphorylated to 2-[18F]-FDG-6-phosphate. The following dephosphorylation step is slow and the labeled compound is retained over several hours within the cells. Non-metabolized 2-[18F]-FDG is excreted rapidly in the urine to an extent of about 16% after 60 min, and 50% after 135 min, respectively. Fluorine-18F decays by emission of 511 KeV gamma photons. The whole body effective dose is reported to be 21 to 27 microSv/MBq. In case of an intravenous injection of 370 MBq this leads to a total dose of 7.8 to 10 mSv. The critical organ is the bladder wall (radiation dose 120 to 170 microSv/MBq or 80 to 100 mrem/mCi). The risk of a radiation induced late malignoma at 10 mSv can be estimated to be 1:2000. The genetical risk as a consequence of FDG-PET diagnostics would be 1:100,000 to 2:100,000 for dominant, and 5 times higher for recessive mutations.

[Combination therapy of endemic goiter with two different thyroxine/iodine combinations]. / Studie zur Kombinationstherapie der endemischen Struma mit zwei unterschiedlichen Thyroxin/Iodkombinationen.

AIM: Of this study was to investigate the extent of thyrotropin (TSH) suppression and volume reduction in combination therapy of endemic goitre. We compared an individually adapted dose of thyroxine with a fixed dose. METHODS: 105 patients of a multicenter study (randomised, single blinded, controlled) received daily a weight-adjusted LT4-dose in combination with 150 micrograms iodide (group A) or a fixed combination of 100 micrograms LT4 plus 100 micrograms iodide (group B), respectively. At the beginning and after 12 weeks TSH-levels and goitre volume were examined. RESULTS: Although the amount of thyrotropin suppression showed no differences in both groups, there were more patients in the weight-adjusted treatment group with completely suppressed thyrotropin serum concentrations (p < 0.05). Both groups showed a reduction of goitre volume of 24% CONCLUSION: A weight-adjusted LT4-dose of 1.4 micrograms/kg body weight often leads to subclinical hyperthyroidism. To obtain low TSH-levels without complete suppression LT4-doses of 1.0 microgram/kg body weight plus 150 micrograms iodide are probably sufficient.