Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients. Trattamento chirurgico degli schwannomi vestibolari: risultati su una serie di 1006 pazienti

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare l’evoluzione negli esiti chirurgici dell’exeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente l’asportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dell’ultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado HouseBrackmann), con una variazione tra il primo e l’ultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione dell’udito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). L’udito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nell’ultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dell’asportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione dell’udito, le perdite di liquido cefalorachidiano, principalmente grazie all’esperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall’ esperienza maturata sulle lesioni di piccole dimensioniThe management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team's experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients = Trattamento chirurgico degli schwannomi vestibolari: Risultati su una serie di 1006 pazienti

The management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team’s experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

ACTA OTORHINOLARYNGOLOGICA ITALICA

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare levoluzione negli esiti chirurgici dellexeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente lasportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dellultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado House- Brackmann), con una variazione tra il primo e lultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione delludito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). Ludito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nellultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dellasportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione delludito, le perdite di liquido cefalorachidiano, principalmente grazie allesperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall esperienza maturata sulle lesioni di piccole dimensioni

Neurofibromatosis 2011: a report of the Children's Tumor Foundation annual meeting.

The 2011 annual meeting of the Children's Tumor Foundation, the annual gathering of the neurofibromatosis (NF) research and clinical communities, was attended by 330 participants who discussed integration of new signaling pathways into NF research, the appreciation for NF mutations in sporadic cancers, and an expanding pre-clinical and clinical agenda. NF1, NF2, and schwannomatosis collectively affect approximately 100,000 persons in US, and result from mutations in different genes. Benign tumors of NF1 (neurofibroma and optic pathway glioma) and NF2 (schwannoma, ependymoma, and meningioma) and schwannomatosis (schwannoma) can cause significant morbidity, and there are no proven drug treatments for any form of NF. Each disorder is associated with additional manifestations causing morbidity. The research presentations described in this review covered basic science, preclinical testing, and results from clinical trials, and demonstrate the remarkable strides being taken toward understanding of and progress toward treatments for these disorders based on the close interaction among scientists and clinicians

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was &gt;20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was &gt;20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to &gt; 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Abstract Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. </jats:sec

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS