MRI-based contrast clearance analysis shows high differentiation accuracy between radiation-induced reactions and progressive disease after cranial radiotherapy.

BACKGROUND: Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared with progressive disease (PD). We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging-based contrast clearance analysis (CCA) in this clinical setting. PATIENTS AND METHODS: Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. CCA was carried out by software-based automated subtraction of imaging features in late versus early T1-weighted sequences after contrast agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for histological findings. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically. RESULTS: A total of 33 patients were included; 16 (48.5%) were treated because of a primary brain tumor (BT), and 17 (51.1%) because of a secondary BT. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 [95% confidence interval (CI) 0.67-0.95; one-sided P = 0.051; n = 32]. Sensitivity and specificity of CCA were 0.93 (95% CI 0.66-1.00) and 0.78 (95% CI 0.52-0.94), respectively. The accuracy in patients with secondary BTs was 0.94 (95% CI 0.71-1.00) and nonsignificantly higher compared with patients with primary BT with an accuracy of 0.73 (95% CI 0.45-0.92), P = 0.16. CONCLUSIONS: In this study, CCA was a highly accurate, easy, and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in patients with secondary tumors after radiosurgical treatment.

[Muscle weakness and CK elevation: is it myositis?] / Muskelschwäche und CK­Erhöhung: Ist es immer eine Myositis?

Rheumatologists are often confronted by patients with muscle weakness and elevated creatine kinase (CK) levels. Myositis cannot always be determined to be the cause of the complaints. This article presents two cases from our hospital where the diagnosis could only be determined by muscle biopsy. In the first case the patient presented with muscle weakness, pathological weight loss and a significant increase in CK levels. A muscle biopsy revealed an immune-mediated necrotizing myopathy (IMNM) caused by anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMG-CoA reductase) autoantibodies due to the intake of statins. The second patient presented with cramp-like and burning muscle pain and weakness of the extremities without a relevant increase in CK level. Myoadenylate deaminase deficiency was also detected by muscle biopsy, and further confirmed by genetic testing.

Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.

OBJECTIVE: We evaluated the clinical feasibility of a new injection technique for sentinel detection in endometrial carcinoma (EC), transcervical subepithelial injection into the isthmocervical region of the myometrium. We compared detection of sentinel lymph nodes (SLN) by single photon emission computed tomography with CT (SPECT/CT) with planar lymphoscintigraphy. METHODS: This is a unicentric prospective study. In all patients, transcervical injection of 10 MBq Technetium-99m-nanocolloid was performed into the isthmocervical myometrium without anaesthesia. After 40 (30-60) min, lymphoscintigraphy and SPECT/CT were performed. Patent blue was administered before surgery. The number and localisation of SLN detected in SPECT/CT and lymphoscintigraphy were recorded and compared to the SLN and non-SLN dissected intra-operatively. RESULTS: Between August 2008 and March 2012, 31 patients with EC were enrolled. The new transcervical injection of labelling substances led to high intra-operative (90.3%) detection rates, pelvic bilateral (57%), para-aortic (25%). SPECT/CT significantly identified more SLN than lymphoscintigraphy (mean 2.2 (1-8) to 1.3 (1-7)) in more patients (29/31 (93.5%) to 21/31 (68%), p<0.01). If SLN were identified in one hemi-pelvis, the histological evaluation of the SLN correctly predicted lymph node (LN) metastases for this basin which led to sensitivity 100%, negative predictive value (NPV) 100%, and false negative results 0%. CONCLUSION: Transcervical SLN marking in combination with SPECT/CT is easily applicable and leads to high physiologic detection rates in pelvic and para-aortic lymphatic drainage areas. Non-affected SLN truly predicted a non-affected LN basin. Combining both methods SLN dissection may be a safe and feasible staging technique for clinical routine in EC.

Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

Cardio-facio-cutaneous (CFC) and Costello syndrome (CS) are congenital disorders with a significant clinical overlap. The recent discovery of heterozygous mutations in genes encoding components of the RAS-RAF-MAPK pathway in both CFC and CS suggested a similar underlying pathogenesis of these two disorders. While CFC is heterogeneous with mutations in BRAF, MAP2K1, MAP2K2 and KRAS, HRAS alterations are almost exclusively associated with CS. We carried out a comprehensive mutation analysis in 51 CFC-affected patients and 31 individuals with CS. Twelve different BRAF alterations were found in twenty-four patients with CFC (47.0%), two MAP2K1 mutations in five (9.8%) and two MAP2K2 sequence variations in three CFC-affected individuals (5.9%), whereas three patients had a KRAS alteration (5.9%). We identified four different missense mutations of HRAS in twenty-eight cases with CS (90.3%), while KRAS mutations were detected in two infants with a phenotype meeting criteria for CS (6.5%). In 14 informative families, we traced the parental origin of HRAS alterations and demonstrated inheritance of the mutated allele exclusively from the father, further confirming a paternal bias in the parental origin of HRAS mutations in CS. Careful clinical evaluation of patients with BRAF and MAP2K1/2 alterations revealed the presence of slight phenotypic differences regarding craniofacial features in MAP2K1- and MAP2K2-mutation positive individuals, suggesting possible genotype-phenotype correlations.

In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time-domain mammograms.

A valuable method is described to analyze time-domain optical mammograms measured in the slab-like geometry of the slightly compressed female breast with a method based on linear perturbation theory including edge correction. Perturbations in scattering and absorption coefficients were mapped applying a computationally efficient point model.

Variability in the Proteus syndrome: report of an affected child with progressive lipomatosis.

In 1983 the Proteus syndrome was delineated by Wiedemann et al. [12]. We report a 10-month-old girl, a further child affected by the new syndrome. The typical signs are macrodactyly, hemihypertrophy, pigmented nevi, hyperkeratosis, and subcutaneous hamartomatous tumours. Our patient shows an aggressive lipomatosis on the trunk and local relapses after surgical interventions in the regions involved. Histology of the adipose tissue showed considerable anisocytosis and increased cell volume.

Clinical diagnosis of malformation syndromes: syndromatology in paediatrics.

The term malformation syndrome should be retained for designation of characteristic symptom complexes of clear-cut pathogenesis. Classification of disorders into any of the three categories deformation, malformation respectively dysplasia or into any combination of them leads to better insight into morphological syndromes. Ten rules of the diagnostic procedure have been formulated and illustrated by the example of the Beckwith-Wiedemann syndrome. Disturbed organogenesis is usually accompanied by multiple signs of dysmorphy, a careful search for malformations is therefore desirable. In the case of malformation syndromes interfering with growth and development continuous care of the patient is indispensable.

[The analysis of chromosomes today: aspects of the technic with indications and importance of the method]. / Die Chromosomenanalyse heute: Aspekte zur Technik, Indikationsstellung und Bedeutung der Methode.

0.5 to 1% of all newborn possess a chromosomal aberration. In a growing number of neoplasias chromosomal disturbances become known. 10 years after the introduction of the band technique into cytogenetics this method must be regarded as most essential progress in the description of chromosomes. Apart from the exact identification of each individual chromosome the band technique allows the exact establishment of fraction points and gives the possibility of new progress in the gene tabulation. With the help of instances some of these possibilities are demonstrated. Prerequisite for the effective use of the analysis of chromosomes is a strong indication. An indication catalogue concerning the clinical application of the method summarizes the essential problems from paediatrics, gynaecology and internal medicine.