http://repub.eur.nl/res/aut/31138/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39461/ 2013-03-19T00:00:00Z Objective: Largely, watchful waiting is the initial policy for patients with small-sized or medium-sized vestibular schwannoma, because of slow growth and relatively minor complaints, that do not improve by an intervention. If intervention (microsurgery, radiosurgery or fractionated radiotherapy) becomes necessary, the choice of intervention appears to be driven by the patient's or clinician's preference rather than by evidence based. This study addresses the existing evidence based on controlled studies of these interventions. Design: A systematic Boolean search was performed focused on controlled intervention studies. The quality of the retrieved studies was assessed based on the Sign-50 criteria on cohort studies. Data sources: Pubmed/Medline, Embase, Cochrane Central Register of Controlled Trials and reference lists. Study selection: Six eligibility criteria included a controlled intervention study on a newly diagnosed solitary, vestibular schwannoma reporting on clinical outcomes. Two prospective and four retrospective observational, controlled studies published before November 2011 were selected. Data analysis: Two reviewers independently assessed the methodological quality of the studies and extracted the outcome data using predefined formats. Results: Neither randomised studies, nor controlled studies on fractionated radiotherapy were retrieved. Six studies compared radiosurgery and microsurgery in a controlled way. All but one were confined to solitary tumours less than 30 mm in diameter and had no earlier interventions. Four studies qualified for trustworthy conclusions. Among all four, radiosurgery showed the best outcomes: there were no direct mortality, no surgical or anaesthesiological complications, but better facial nerve outcome, better preservation of useful hearing and better quality of life. Conclusions: The available evidence indicates radiosurgery to be the best practice for solitary vestibular schwannomas up to 30 mm in cisternal diameter. http://repub.eur.nl/res/pub/24539/ 2009-08-01T00:00:00Z Background: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods: Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings: SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding: The Netherlands Organisation for Scientific Research, Dutch Cancer Society, Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Santé et de la Recherche Médicale, and a PHRC grant COMETE 3 for the COMETE network.