Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. Conclusion: This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. Clinicaltrials. gov-Nr: NCT02181049.

Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma.

Anaplastic large cell lymphoma (ALCL) is a main type of T-cell lymphomas and comprises three distinct entities: systemic anaplastic lymphoma kinase (ALK) positive, systemic ALK(-) and cutaneous ALK(-) ALCL (cALCL). Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK(-) ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of five ALK(+) and four ALK(-) systemic ALCL, seven cALCL and sixteen cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4(+), CD8(+) or CD30(+) T-cell origin. Indeed, ALCL display a down-modulation of many T-cell characteristic molecules. All ALCL types show significant expression of NFkappaB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly, few genes are differentially expressed between systemic and cALCL despite their different clinical behaviour, and between ALK(-) ALCL and cHL despite their different cellular origin. ALK(+) ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.

The value of FDG-PET and bone scintigraphy with SPECT in the primary diagnosis and follow-up of patients with chronic osteomyelitis of the mandible.

OBJECTIVE: To appraise the value of FDG-PET and bone scintigraphy using SPECT in the primary diagnosis and follow-up of patients with chronic osteomyelitis of the mandible (COM). METHODS: In a prospective study the pattern of tracer uptake was investigated using 2 diagnostic methods in 42 patients. Results were compared with histology and radiographs as well as clinical and laboratory parameters. RESULTS: The use of FDG-PET in the primary diagnosis of COM resulted in a sensitivity of 64% and a specificity of 77.7%. The sensitivity of SPECT was 84% and the specificity 33.3%. During the follow-up period of these patients the sensitivity of SPECT increased to 93.7%, while the specificity decreased (6.6%). The sensitivity and specificity of FDG-PET for this follow-up group were 62.5 and 80%, respectively. CONCLUSION: Because of its high sensitivity, SPECT is vastly superior to other diagnostic methods in initiating treatment. In the follow-up period it might be replaced by FDG-PET, which reflects the disease course better and indicates the time of clinical remission.

[Esophageal scintigraphy of Zenker's diverticula before and after diverticulotomy]. / Osophagusszintigraphie von Zenkerschen Divertikeln vor und nach Divertikulotomie.

AIM: The filling and evacuation of Zenker's diverticula were scintigraphically examined before and after operation to quantify their functional relevance. These results were correlated with the symptoms of the patients and the findings of the barium swallow x-ray examination using cineradiography. METHODS: Sequential and static esophageal scintigraphies were performed in 17 patients with Zenker's diverticulum before and after laser surgical diverticulotomy. We used a gamma camera system in 45 degrees LAO-position after application of 15 ml of tea which was marked with 99mTc-DTPA. Filling and evacuation of the diverticulum were expressed in proportion to the administered activity. Relative volumes of the diverticula were obtained from cineradiography by using the height of the neighbouring cervical vertebra, and the clinical symptoms were divided into 4 groups. RESULTS: Zenker's diverticula could be verified visually and quantitatively by scintigraphy. The precise temporal course of the reduction of activity in the diverticulum was exactly determined. The scintigraphic retentions correlated with the x-ray volumes with a coefficient ranging from 0.55 to 0.85. Clinical symptoms also were not very closely related to scintigraphic and x-ray findings, respectively. CONCLUSION: The esophageal scintigraphy allows quantification of the filling and evacuation of Zenker's diverticula, thus it is suitable for objectivization of the functional relevance of the diverticula. That's why the esophageal scintigraphy should be taken to the diagnosis of diverticula in addition to the clinic and the x-ray examinations. The method is especially useful to evaluate the results after diverticulotomy.