Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. Accumulation of viscous, poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its operational mechanisms have not been resolved. Herein, we report that positively charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively charged NPs can significantly reduce the rate of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications

THE OCCIPITAL TRANS-TENTORIAL APPROACH TO PINEAL REGION TUMORS

BACKGROUND The Occipital Trans-Tentorial approach (OTT) to pineal region was popularized by Poppen in 1966. The 'so-called' Poppen's approach offers some unquestionable advantages in the treatment of those pineal tumors extending superioriorly above the tentorial edge, inferioriorly into the cerebellomesencephalic fissure and/or laterally beyond the medial borders of the tentorium. The authors report a step-by-step description of the OTT approach also highlighting the tips and the triks of this approach and the advantages related to a supratentorial surgical perspective to pineal area and posterior fossa. MATERIALS AND METHODS A stepwise description of the OTT approach has been reported. Some surgical cases from a personal series of 20 pineal tumors treated in a range period of 10 years (2004-2014) have been furthermore reviewed and discussed. RESULTS OTT approach involves a midline or L-shaped skin incision extending more above than below the inion to skeletonize the occipital squama and the external occipital protuberance. The inion serves as an important landmark to identify the torcular. A burr hole has to be placed on the external occipital protuberance and along the superior sagittal and ipsilateral transverse sinuses to perform a paramedian supratentorial occipital craniotomy. Extremely care should be taken to avoid injuries to the sinuses. Opening of the dura above the tranverse sinus and immediately lateral to the superior sagital sinus allows for a posterior inter emispheric exposure of the ipsilateral tentorium. The trans-tentorial access to the pineal region and the posterior third ventricle involves the caoagulation, cutting and reflection of the tentorium. This allows for a sub-occipital trans-tentorial perspective of the pineal region. In the personal series the OTT approach has been employed alone or in a combination with the infratentorial supracerebellar approach (ITSC) to treat different kind of lesions involving the pineal region. Compared with the ITSC, OTT approach has resulted more suitable and advantageous exspecially in those lesions with a para median or more cephalad extension. CONCLUSIONS The OTT approach is very useful to treat those pineal tumors caraharacterized by a para-mediam extension and/or involving the posterior third ventricle. The reflection of the tentorium provides an excellent and wide view of the pineal region both from above and from below. A detailed knowledge of the anatomy of this region, as well as the different steps of the approach are both of utmost importance to execute safely the approach

THE OCCIPITAL TRANS-TENTORIAL APPROACH TO PINEAL REGION TUMORS

BACKGROUND The Occipital Trans-Tentorial approach (OTT) to pineal region was popularized by Poppen in 1966. The 'so-called' Poppen's approach offers some unquestionable advantages in the treatment of those pineal tumors extending superioriorly above the tentorial edge, inferioriorly into the cerebellomesencephalic fissure and/or laterally beyond the medial borders of the tentorium. The authors report a step-by-step description of the OTT approach also highlighting the tips and the triks of this approach and the advantages related to a supratentorial surgical perspective to pineal area and posterior fossa. MATERIALS AND METHODS A stepwise description of the OTT approach has been reported. Some surgical cases from a personal series of 20 pineal tumors treated in a range period of 10 years (2004-2014) have been furthermore reviewed and discussed. RESULTS OTT approach involves a midline or L-shaped skin incision extending more above than below the inion to skeletonize the occipital squama and the external occipital protuberance. The inion serves as an important landmark to identify the torcular. A burr hole has to be placed on the external occipital protuberance and along the superior sagittal and ipsilateral transverse sinuses to perform a paramedian supratentorial occipital craniotomy. Extremely care should be taken to avoid injuries to the sinuses. Opening of the dura above the tranverse sinus and immediately lateral to the superior sagital sinus allows for a posterior inter emispheric exposure of the ipsilateral tentorium. The trans-tentorial access to the pineal region and the posterior third ventricle involves the caoagulation, cutting and reflection of the tentorium. This allows for a sub-occipital trans-tentorial perspective of the pineal region. In the personal series the OTT approach has been employed alone or in a combination with the infratentorial supracerebellar approach (ITSC) to treat different kind of lesions involving the pineal region. Compared with the ITSC, OTT approach has resulted more suitable and advantageous exspecially in those lesions with a para median or more cephalad extension. CONCLUSIONS The OTT approach is very useful to treat those pineal tumors caraharacterized by a para-mediam extension and/or involving the posterior third ventricle. The reflection of the tentorium provides an excellent and wide view of the pineal region both from above and from below. A detailed knowledge of the anatomy of this region, as well as the different steps of the approach are both of utmost importance to execute safely the approach

DECOMPRESSION CRANIOTOMY – PERSONAL EXPERIENCE

INTRODUZIONE La craniotomia decompressiva rappresenta una procedura chirurgica che comprende la rimozione temporanea di una porzione di cranio al fine di alleviare gli effetti secondari dell’ipertensione intracranica. Può essere ottenuta mediante l’asportazione di osso a livello fronto-temporo-occipitale, sia monolaterale che bilaterale, oppure attraverso una craniotomia bifrontale. Il risultato di un danno primario quale l’edema cerebrale conseguente ad un’ischemia, un’emorragia cerebrale o un ematoma occupante spazio può condurre a un aumento della pressione intracranica che, all’interno di un contenitore a volume fisso come il cranio, può rapidamente portare a danni secondari del parenchima cerebrale o addirittura alla morte. MATERIALI E METODI Nella nostra U.O., la craniotomia decompressiva è considerata un valido trattamento nei casi di ipertensione intracranica severa. Per questo motivo, viene praticata sia in forma primaria che secondaria. Per craniotomia decompressiva primaria si intende una decompressione chirurgica che si esegue durante l’evacuazione di un ematoma sottodurale acuto o intraparenchimale spontaneo o traumatico quando si ravvisa, come profilassi o per la presenza di edema cerebrale massivo, la necessità di non riposizionare l’opercolo osseo. Differentemente, la craniotomia decompressiva secondaria rientra nel trattamento dell’ipertensione intracranica non responsiva ai normali trattamenti farmacologici e viene effettuata al riscontro di valori di pressione intracranica (PIC) costantemente superiori ai 20 mmHg. RISULTATI Nel periodo compreso tra marzo 2008 e marzo 2013, abbiamo eseguito 32 craniotomie decompressive in 28 pazienti (in 3 pazienti la decompressione è stata bilaterale, mentre un paziente è stato decompresso anche in fossa cranica posteriore). L’età media è stata di 45,5 anni (minima 14; massima 85) con un rapporto maschi/femmine di 1,2 per una leggera prevalenza del sesso maschile (15 casi) su quello femminile (13 casi). Per ragioni statistiche e per rendere i dati confrontabili con le casistiche pubblicate nella letteratura internazionale, i pazienti sono stati raggruppati in tre macrocategorie in base all’evento patologico che ha portato alla necessità dell’intervento di craniotomia decompressiva: trauma, ischemia ed emorragia. In particolare, 14 pazienti (50 %) sono stati trattati in seguito a eventi traumatici, 6 pazienti (21,4 %) per ischemia cerebrale e 8 pazienti (28,6 %) per eventi emorragici. Nello specifico, all’interno della categoria “trauma” sono stati inseriti i soggetti affetti da ematoma sottodurale acuto mono o bilaterale, contusioni cerebrali o danno assonale diffuso; nella categoria “ischemia” sono andati i soggetti affetti da ischemie cerebrali post-chirurgiche (dopo clipping di aneurisma cerebrale, dopo posizionamento di stent endovascolari o dopo tromboendoarteriectomia carotidea); infine, nella categoria “emorragia” sono stati considerati i pazienti affetti da emorragie intraparenchimali spontanee o da rottura di malformazioni artero-venose e pazienti con emorragia subaracnoidea da aneurisma cerebrale. Nessuno dei 6 pazienti trattati per ischemia cerebrale era affetto da ictus cerebri, ma in tutti i casi l’infarto cerebrale è stato secondario alla manipolazione chirurgica o endovascolare. CONCLUSIONI La mortalità generale è stata del 32,1 %: 9 soggetti deceduti, di cui 5 maschi e 4 femmine. La metà dei soggetti decompressi per causa emorragica è deceduta, mentre la mortalità dei pazienti con ischemia cerebrale è inferiore al 20 %: un deceduto su 6 trattati. Per quanto riguarda l’outcome generale, il punteggio mRS medio (modified Rankin Scale) è stato di 4, configurando un profilo comune di disabilità grave seppur associata a un adeguato stato di vigilanza e coscienza. Scegliendo due cut off di età a 30 e a 60 anni che meglio rappresentano la popolazione in studio, avendo un’età media relativamente bassa, è stato possibile riscontrare che non ci sono sostanziali differenze di outcome nei soggetti più giovani rispetto ai più anziani, pur riscontrando in quest’ultimi una disabilità più grave, come ci si aspetterebbe. Anche la valutazione dell’outcome in base al sesso, non mostra differenze tra i due gruppi che sono sostanzialmente omogenei per composizione. Infine, l’outcome per causa sottolinea un andamento peggiore nei soggetti sottoposti a craniotomia decompressiva per emorragia intraparenchimale spontanea o emorragia subaracnoidea da rottura di aneurisma cerebrale

THE INFRA-TENTORIAL SUPRACEREBELLAR APPROACH

BACKGROUND The Infra-tentorial Supracerebellar approach (ITSC) to pineal region was described by Krause in 1911 and refined and popularized by Stein in 1982.Basically, ITSC offers an optimal exposure of the area between the vein of Galen complex and the cerebellomesencephalic fissure, so it is very useful for small to medium sized tumors confined to the micline and/or having a minimal para-median infratentorial extension. The authors critically review the personal series of pineal tumors removed via ITSC approach, also focusing on the selection criteria in the choice of the most suitable approach to pineal tumors. MATERIALS AND METHODS A wide review of pineal tumors treated in a range of 10 years (2004-2014) has been performed, with special emphasis to those cases treated via an ITSC route. This review regarded the type of lesion, indications to ITSC approach, choice of patient surgical position, complications and outcome. RESULTS In a range period of 10 years, 36 pineal region tumors have been treated. Among these, 15 were men and 21 female. The mean age was 43.1 years. The size of lesions were <3 cm in 30 cases and ≥3 cm in 6 cases. All lesions (14 meningiomas, 7 low grade gliomas, 2 high grade gliomas, 3 hemangioblastomas, 2 cavernomas, 2 pinealomas, 2 metastases, 2 dysgerminomas, 1 schwannoma, 1 medulloblastoma) were completely resected. In 16 cases an ITSC approach was performed, whereas an occipital trans-tentorial approach was employed in 20 cases. All tumors were completely removed surgically without any injury to the venous complex. There was no incidence of mortality or morbidity in our group of patients, and all functional outcomes were good to excellent postoperatively. CONCLUSIONS Pineal region is among the most complex intracranial areas to be reached mainly due to its deep location and the obstacle posed by the vascular structures in the midline. It derives that tumours involving this region are some of the most difficult lesions to expose and remove. Our review suggests that ITSC approach is an useful and safe approach, with a very low morbidity and zero mortality, for removing those pineal tumors with a midline infratentorial extension

PINEAL REGION TUMORS: SURGICAL MANAGEMENT AND PERSONAL EXPERIENCE

BACKGROUND The pineal region is one of the most complex regions to access because of its deep location, as well the presence of many neurovascular structures forming a natural obstacle to the surgical route. The repertoire of the surgical approaches to the pineal region has evolved considerably over the past 100 years, with an associated decline in operative mortality from 100% to less than 4%. The authors critically review the personal series of pineal region tumors focusing on the operative approaches most frequently used in dealing these lesions. MATERIALS AND METHODS A series of pineal and para-pineal tumors has been selected from the personal tumors’ registry. A wide review regarding the type of lesions, surgical positions, type of approaches and selection criteria for a specific type of approach has been performed. RESULTS In a range period of 10 years, 36 pineal tumors have been treated. Among these, 15 were men and 21 female. The mean age was 43.1 years. The most frequent lesion observed was 14 tentorial meningiomas. The most frequently employed approaches were the occipital trans-tentorial and supra-cerebellar infratentorial. All tumors were completely removed surgically without any injury to the venous complex. There was no incidence of mortality or morbidity in our group of patients, and all functional outcomes were good to excellent postoperatively. CONCLUSIONS Pineal tumors are considered challenging lesions very difficult to treat. According to the personal experience, the occipital trans-tentorial approach and the supra-cerebellar infratentorial approach with the patient in the prone, sitting or semi-sitting position are the most useful approach for the treatment of these lesions. A perfect knowledge of the anatomy of this region is to be considered mandatory to perform safely these kinds of approaches

SURGICAL ANATOMY AND APPROACHES TO THE PINEAL REGION

Background: pineal gland is a diencephalic structure related to the posterior wall of the third ventricle and lying between the superior colliculi of the quadrigeminal plate. It gives the name to a specific topographic region called pineal region. Lesions involving the pineal region are considered very difficult to treat mainly due to the deep site of the gland, as well the intimate relationships these lesions have with the deep venous system. A perfect knowledge of the microneurosurgical anatomy of this region is of utmost importance to deal with pineal tumors and, at the same time, to make safer all the approaches to the pineal region. Materials and Methods: the authors review in detail the microneurosurgical anatomy of the pineal region focusing on those anatomical aspects related to the different pattern of tumor growth and playing a pivotal role in the choice of the most suitable and advantageous approach among others. The occipital trans-tentorial approach and the supra-cerebellar infratentorial approach have also been reviewed in detail with reference to some surgical cases. Results: pineal region is bounded laterally by the tentorial edge and the thalami, rostrally by the posterior third ventricle, caudally by the vermis of the cerebellum, ventrally by the quadrigeminal plate and dorsally by the splenium of the corpus callosum. Pineal gland is oval in shape and measures, on the average, 7.4 mm in longitudinal length, 6.9 mm in transverse width, and 2.5 mm in thickness. Its arterial supply belongs to the pineal artery, one of the branches of the medial posterior choroidal artery (MPChA), whereas the venous outflow is realized by means of the pineal vein that empty into the Galenic system. The distance between the pineal gland and the tentorial notch ranges from 10 to 30 mm. The arteries that run within the pineal region and posterior incisural space are as follow: P2 posterior and P3 segments of posterior cerebral artery (PCA), circumflex artery from P1 segment of PCA, thalamo-geniculate artery from P1 segment of PCA, MPChA from P2 anterior segment of PCA, lateral posterior choroidal artery from P2 posterior segment of PCA, cortical branches of PCA, that are the inferior temporal artery, parieto-occipital artery, calcarine artery, and splenial artery and distal segment of superior cerebellar artery. Regarding the venous structures, the pineal region holds the vein of Galen, formed by the union of the paired internal cerebral veins, the paired basal veins of Rosenthal, the inferior ventricular vein, lateral and posterior mesencephalic veins, internal occipital vein, posterior pericallosal vein, straight sinus and a number of bridging veins from the tentorial surface of the cerebellum, especially in the midline. The fourth cranial nerve emerges posteriorly below the inferior colliculi of the quadrigeminal plate and passes trough the quadrigeminal cistern in the pineal region in its forward direction. Occipital trans-tentorial approach is mainly indicated for those cases where the distance between the pineal gland and the tentorial notch is less than 20 mm and/or the lesion encroaches the posterior part of the third ventricle. On the other hand, the supra-cerebellar infra-tentorial approach offers the best view and working space for those lesions having a caudal infratentorial extension, even though it should be always considered the unavoidable sacrifice of the bringing veins from the tentorial surface of the cerebellum. A combined approach is also very useful for those lesions having a supra and infra-tentorial extension. Conclusion: the majority of pineal region tumors can be safely approached either via the supra-cerebellar infra-tentorial approach or the occipital trans-tentorial approach. An extremely detailed knowledge of the anatomy of this region is mandatory in the selection and execution of all of these approaches

PINEAL REGION TUMORS: SURGICAL MANAGEMENT AND PERSONAL EXPERIENCE

BACKGROUND The pineal region is one of the most complex regions to access because of its deep location, as well the presence of many neurovascular structures forming a natural obstacle to the surgical route. The repertoire of the surgical approaches to the pineal region has evolved considerably over the past 100 years, with an associated decline in operative mortality from 100% to less than 4%. The authors critically review the personal series of pineal region tumors focusing on the operative approaches most frequently used in dealing these lesions. MATERIALS AND METHODS A series of pineal and para-pineal tumors has been selected from the personal tumors’ registry. A wide review regarding the type of lesions, surgical positions, type of approaches and selection criteria for a specific type of approach has been performed. RESULTS In a range period of 10 years, 36 pineal tumors have been treated. Among these, 15 were men and 21 female. The mean age was 43.1 years. The most frequent lesion observed was 14 tentorial meningiomas. The most frequently employed approaches were the occipital trans-tentorial and supra-cerebellar infratentorial. All tumors were completely removed surgically without any injury to the venous complex. There was no incidence of mortality or morbidity in our group of patients, and all functional outcomes were good to excellent postoperatively. CONCLUSIONS Pineal tumors are considered challenging lesions very difficult to treat. According to the personal experience, the occipital trans-tentorial approach and the supra-cerebellar infratentorial approach with the patient in the prone, sitting or semi-sitting position are the most useful approach for the treatment of these lesions. A perfect knowledge of the anatomy of this region is to be considered mandatory to perform safely these kinds of approaches

SKULL BASE APPROACHES FOR BASILAR ARTERY ANEURYSMS

INTRODUZIONE Gli aneurismi dell’arteria basilare sono sempre da considerarsi lesioni ad altissima complessità chirurgica in ragione della loro posizione anatomica, della difficoltà di accesso chirurgico e degli intimi rapporti col tronco encefalico e con i nervi cranici. Se comparati con quelli del circolo anteriore, questi aneurismi presentano più frequentemente grandi dimensioni, trombosi endo-luminale e fenomeni di sclerosi a livello della sacca aneurismatica e/o dell’arteria d’origine. La scelta dell’approccio chirurgico è ampiamente condizionata dalla localizzazione dell’aneurisma, dall’ovvia necessità di ottenere un controllo vascolare prossimale del vaso d’origine e da fattori anatomici intrinseci quali la proiezione dell’apice dell’arteria basilare rispetto alla linea bi-clinoidea posteriore. Ulteriori fattori da considerare sono le dimensioni e la proiezione dell’aneurisma, la presenza di eventuale trombosi intra-luminale, l’emergenza di vasi efferenti dalla sacca aneurismatica e/o la necessità di prevedere una procedura di rivascolarizzazione del circolo posteriore. Questo studio è basato su una review dei principali approcci chirurgici, utilizzati nella nostra casistica, per il trattamento degli aneurismi dell’arteria basilare. MATERIALI E METODI La serie è basata su un gruppo complessivo di 100 aneurismi dell’arteria basilare operati dal Marzo 1993 al Marzo 2014. 75 aneurismi erano localizzati sull’apice dell’arteria basilare, 12 a livello del tronco comune dell’arteria basilare e 13 a livello della giunzione vertebro-basilare. 14 aneurismi presentavano dimensioni “giants”, 17 “very large” ed i restanti 69 “regular”. 63 di questi aneurismi erano rotti e i rimanenti 37 non rotti. Gli approcci utilizzati sono stati scelti in base alla posizione anatomica dell’aneurisma relativamente al segmento dell’arteria basilare: apice, tronco comune e giunzione vertebro-basilare. Per gli aneurismi dell’apice dell’arteria basilare sono stati utilizzati l’approccio ptèrionale “extended” e l’approccio fronto-orbito-temporo-zigomatico. Per gli aneurismi del tronco comune dell’arteria basilare è stato utilizzato l’approccio trans-petroso combinato. Per gli aneurismi della giunzione vertebro-basilare è stato utilizzato l’approccio postero-laterale (far lateral). RISULTATI L’approccio ptèrionale “extended” (one layer), comprensivo di clinoidectomia posteriore è stato utilizzato per aneurismi small/regular e con proiezione mai superiore rispetto alla linea bi-clinoidea posteriore. Per gli aneurismi di top di basilare con proiezione “alta” del punto di biforcazione dell’arteria, ovvero superiore rispetto alla linea bi-clinoidea posteriore, è stato utilizzato l’approccio fronto-orbito-temporo-zigomatico (two layer) “three-pieces” comprensivo di mobilizzazione dell’arcata zigomatica, clinoidectomia anteriore intra o extradurale, unroofing del canale ottico, cutting del distaldural ring carotideo, mobilizzazione della carotide, con o senza clinoidectomia posteriore intradurale trans-cavernosa. Negli aneurismi del tronco comune dell’arteria basilare è stato utilizzato l’approccio trans-petroso combinato pre-sigmoideo comprensivo di apicectomia della rocca petrosa, sezione del seno petroso superiore e cutting del tentorio. Nel caso di aneurismi della giunzione vertebro-basilare è stato invece utilizzato l’approccio postero-laterale (far lateral) generalmente juxta o para-condilare, ovvero, nella quasi totalità dei casi, con risparmio dell’integrità anatomica del condilo occipitale. In questi ultimi non è stato necessario in nessun caso il drilling del tubercolo giugulare. CONCLUSIONI La scelta del coretto approccio chirurgico rappresenta il punto chiave del trattamento degli aneurismi dell’arteria basilare, rotti e non rotti, e non suscettibili di trattamento endovascolare. Il trattamento di questi aneurismi richiede una grande versatilità di scelta tra i principali approcci utilizzati nella chirurgia del basicranio. Una profonda conoscenza dell’anatomia del basicranio e delle strutture neurovascolari è da considerarsi imperativa