Slow cortical potentials neurofeedback in children with ADHD: comorbidity, self-regulation and clinical outcomes 6 months after treatment in a multicenter randomized controlled trial.

Despite sizeable short-term effects of neurofeedback (NF) therapy on attention-deficit and hyperactivity disorder (ADHD), longer-term clinical, comorbidity and self-regulation outcomes are less systematically studied. The aim of this largest NF follow-up to date was to evaluate these outcomes 6 months after NF compared to a semi-active control to disentangle specific from unspecific sustained effects. We performed a multicenter, randomized, parallel, controlled, clinical, superiority trial in five German university outpatient departments. Participants were eligible if they fulfilled DSM-IV-TR criteria for ADHD and were aged from 7 to 9 years. Participants were randomly assigned (1:1-ratio) to 25 sessions of slow cortical potential (SCP)-NF or electromyogram biofeedback (EMG-BF). Participants were not blinded, since they received instructions according to each treatment setting. Primary outcomes were parent ratings of ADHD. The trial was registered, number ISRCTN761871859. Both groups showed improvement of ADHD symptoms compared to baseline at 6-months follow-up with large effect sizes for SCP-NF (d = 1.04) and EMG-BF (d = 0.85), but without group differences. When analyzing all assessments (pre-test, post-test-1, post-test-2 and follow-up), a group-by-time interaction emerged (p = 0.0062), with SCP-NF showing stable improvement following treatment but EMG-BF showing a relapse from post-test-1 to post-test-2, and subsequent remission at follow-up. Six months after the end of treatment, improvement after SCP-NF remained large and stable. However, the lack of group differences at follow-up suggests shared specific and unspecific effects contributing to this clinical outcome. Our correlational results indicate specificity of SCP-NF for selected subscales after training, but not at follow-up.

Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer -what has gone wrong? A blueprint for the way forward in biomarker studies.

BACKGROUND: Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. METHODS: Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. RESULTS: Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. CONCLUSIONS: Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.

[Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)]. / Vancouver-Klassifikation von Nierentumoren : Empfehlungen der Konsenskonferenz der Internationalen Gesellschaft für Uropathologie (ISUP) 2012.

The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.

Sphingosine-kinase-1 expression is associated with improved overall survival in high-grade serous ovarian cancer.

PURPOSE: Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. METHODS: Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). CONCLUSION: Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.

[Hereditary breast and ovarian cancers]. / Hereditäre Mamma- und Ovarialkarzinome.

Hereditary factors are responsible for 5-10% of all breast cancers and 10% of all ovarian cancer cases and are predominantly caused by mutations in the high risk genes BRCA1 and BRCA2 (BRCA: breast cancer). Additional moderate and low penetrance gene variants are currently being analyzed via whole genome association studies. Interdisciplinary counseling, quality managed genetic testing and intensified prevention efforts in specialized medical centres are essential for members of high risk families considering the high prevalence of malignant tumors and the early age of onset. Furthermore, the identification of BRCA-deficient carcinomas is of particular clinical interest, especially regarding new specific therapeutic options, e.g. treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. There are presently no valid surrogate markers verifying the association of BRCA1/BRC2 in tumors. However, breast cancers harboring pathogenic BRCA1 mutations in particular display specific histopathological features.

[Tonsillar lymphangiomatous polyp]. / Lymphangiomatöser Tonsillenpolyp.

Lymphangiomatous polyps are rare benign lesions of the tonsils. We report the case of a female patient presenting with dysphagia of 15 years' standing due to such a lesion. After surgical excision the patient remained free of symptoms and experienced no recurrence (follow-up 17 months). The histology was characterized by epitheliotropism of lymphocytes as well as dilated lymphatic channels, blood vessels and edema. Immunohistochemical staining with D2-40 monoclonal antibody and podoplanin confirmed the diagnosis of lymphangiomatous polyps. We discuss the current literature.