Academic literature on the topic 'Skull base – Surgery'

AbstractLateral skull base pathology is rare in children. Awareness of the potential for lateral skull base lesions in children is imperative for timely identification and appropriate management. Some of the common presentations and pathologies shall be presented, as well as a variety of approaches that may be utilized to access the lateral skull base in the pediatric patient. Although the lateral skull base approaches utilized in adults may also be considered for management of pediatric lesions, some special considerations given the small developing anatomy need to be kept in mind.

Educational objectives: To become familiar with diagnostic and operative management principles for lateral skull-base disease and its ICE, emphasizing not only multi-disciplinary tumor resection but functional outcome and to be familiar with concepts of defect reconstruction and cranial nerve rehabilitation that maximize postresection functional outcome.

Introduzione. I cordomi della base cranica sono tumori rari e a lenta crescita derivanti dalla notocorda. La loro morbilità è principalmente legata alla loro invasione locale e alla resistenza ai trattamenti. A causa del loro aspetto eterogeneo e del loro comportamento clinico-molecolare non completamente compreso, l'obiettivo principale del presente lavoro è quello di identificare marcatori clinici e bio-molecolari come fattori prognostici specifici che potrebbero essere utilizzati per la corretta gestione di tali pazienti. Il raggiungimento di una firma prognostica dettagliata dei cordomi del basicranio è di fondamentale importanza per poter personalizzare il trattamento di ciascun paziente. Inoltre, l'analisi degli sfingolipidi sta emergendo come un nuovo approccio in molti tumori e non è mai stata applicata nei cordomi. L’obiettivo principale è lo studio del comportamento biologico del cordoma e il ruolo della produzione di ceramidi in questo contesto di proliferazione e invasione locale. Pazienti e Metodi. È stata eseguita una revisione retrospettiva di tutti i pazienti diagnosticati e trattati per cordoma della base cranica presso la Fondazione IRCCS Istituto Neurologico "Carlo Besta" tra il gennaio 1992 ed il dicembre 2017. Sono stati raccolti dati clinici, radiologici, chirurgici e patologici. È stata eseguita una raccolta prospettica di campioni chirurgici congelati per analizzare le specie di ceramidi. Gli sfingolipidi sono stati estratti dai tessuti congelati; i ceramidi e i diidroceramidi sono stati valutati mediante cromatografia liquida e spettrometria di massa. L'analisi di sopravvivenza è stata eseguita secondo il metodo di Kaplan-Meier. I confronti univariati sono stati condotti usando i test di Mann-Whitney, Chi-square e il test esatto di Fisher. Sono state condotte analisi di regressione e correlazione lineari. Utilizzando un modello di regressione logistica, i predittori statisticamente significativi sono stati pesati sulla base dei loro odds ratio al fine di sviluppare una scala personalizzata - la Peri-Operative Chordoma Scale (POCS). Risultati. Ottantasette pazienti sono stati trattati chirurgicamente per cordoma del basicranio. Settantotto pazienti sono stati dichiarati eleggibili per la revisione. I pazienti erano 38 maschi (48.7%) e 40 femmine (51.3%). Il follow-up medio era di 69 mesi (intervallo, 3-233). Sono stati eseguiti centoquattordici interventi chirurgici. La presenza di deficit motori si è rivelata essere un fattore prognostico significativo correlato a una PFS peggiore (p=0.0480). La presenza di calcificazioni ha mostrato una correlazione con risultati migliori di OS rispetto al tumore privo di calcificazioni (p=0.0420). Il grado di impregnazione contrastografica alla RM si è rivelato essere un fattore prognostico significativo in termini sia di OS che di PFS (p≤0.0001 e 0.0010, rispettivamente). Il coinvolgimento del forame giugulare e delle cisterne anteriori al tronco encefalico si sono rivelati due fattori prognostici significativi correlati con una riduzione di PFS (p=0.0130 e p=0.0210, rispettivamente). La dislocazione del tronco cerebrale rappresentava un fattore prognostico significativo correlato a peggiore OS e PFS nella coorte di cordomi recidivi (p=0.0060 e 0.0030, rispettivamente). L'estensione della resezione tumorale rappresentava un forte fattore prognostico secondo la PFS nella coorte di cordomi primari (p=0.0200). I pazienti operati da un chirurgo esperto (definito come il chirurgo che ha eseguito più di 10 procedure chirurgiche per cordoma del basicranio nella presente serie) hanno avuto un outcome migliore in termini di PFS nella coorte di pazienti primari (p=0.0340). Lo sviluppo di complicanze post-operatorie in pazienti con cordoma primario rappresentava un importante fattore prognostico correlato sia ad OS che a PFS (p≤0.0001 e 0.0360, rispettivamente). Nella coorte di cordomi recidivi, ∆KPS correlava sia a OS che a PFS (p=0.0010 e 0.0180, rispettivamente). Inoltre, il trattamento radioterapico postoperatorio correlava ad un aumento di OS e PFS (p=0.0020 e p=0.0100, rispettivamente). I seguenti fattori si sono rivelati predittori statisticamente significativi sia di PFS che di OS nel modello di regressione logistica: il grado di impregnazione contrastografica alla RM (intenso o lieve/nessuno), la presenza di deficit motori preoperatori (si o no) e lo sviluppo di complicanze post-operatorie (si o no). Una scala è stata sviluppata con score compresi tra 0 e 17 (Nagelkerke’s pseudo R2=0.656). Le specie totali di ceramidi e diidroceramidi nei cordomi primari erano 808.4±451.4 pmol/mg di proteine (522.5-1760.2) e 30.7±16.4 pmol/mg (17.6-62.4), rispettivamente. Le specie totali di ceramidi e diidroceramidi nei cordomi recidivi erano 1488.1±763.8 pmol/mg (540.7-2787.5) e 67.2±45.5 pmol/mg (9.0-145.6), rispettivamente. Le specie totali di ceramidi erano significativamente più elevate nei cordomi recidivi sottoposti a precedente resezione chirurgica e radioterapia rispetto ai cordomi primari (p=0.0496). Le specie totali di ceramidi e diidroceramidi nel gruppo "intensa impregnazione contrastografica" erano 1597.6±737.8 pmol/mg (592.7-2787.5) e 69.1±45.0 pmol/mg (17.8-145.6), rispettivamente. Le specie totali di ceramidi e diidroceramidi nel gruppo "nessuna o lieve impregnazione contrastografica" erano 664.7±120.4 pmol/mg (522.5-826.0) e 31.5±13.6 pmol/mg (17.6-53.6), rispettivamente. Ceramidi e diidroceramidi totali erano significativamente più alti nei cordomi ad “intensa impregnazione contrastografica” rispetto ai cordomi "nessun o lieve impregnazione contrastografica" (p=0.0290 e p=0.0186, rispettivamente). Analizzando l'associazione tra livelli di ceramidi e MIB-1 all'interno di ciascun paziente con cordoma della base cranica, i livelli di ceramidi totali hanno mostrato un'associazione forte (r=0.7257, r2=0.5267) con la colorazione MIB-1 (p=0.0033). Analizzando l'associazione tra i livelli di diidroceramidi e MIB-1 all'interno di ciascun paziente con cordoma della base cranica, i livelli totali di diidroceramidi hanno mostrato anche un'associazione forte (r=0.6733, r2=0.4533) con MIB-1 (p=0.0083). Tra le singole specie di ceramidi, Cer C24: 1 (r=0.8814, r2=0.7769, p≤0.0001), DHCer C24: 1 (r=0.8429, r2=0.7104, p=0.0002) e DHCer C18:0 (r=0.9426, r2=0.8885, p≤0.0001) hanno mostrato una correlazione significativa con il MIB-1. Conclusioni. L’analisi clinica ha dimostrato che la sintomatologia preoperatoria (deficit motori e a carico dei nervi cranici), la posizione anatomica (forame giugulare, dislocazione del tronco encefalico), le caratteristiche chirurgiche (estensione della resezione tumorale ed esperienza del chirurgo operatore), la presenza di complicanze postoperatorie e il declino del KPS si sono rivelati fattori prognostici significativi. Inoltre, il grado d’impregnazione contrastografica alla RM è stato significativamente correlato sia a OS che a PFS. È stata sviluppata in via preliminare la Peri-Operative Chordoma Scale (POCS) per aiutare il clinico nella gestione personalizzata del paziente che si sottoporrà a potenziali terapie adiuvanti. L’analisi di sfingolipidi, invece, ha evidenziato come i ceramidi possano rappresentare un promettente bio-marcatore nei cordomi. In particolare, i ceramidi a catena lunga e molto lunga, come Cer C24:1 e DHCer C18:0, possono concorrere ad una prolungata sopravvivenza del tumore, aggressività e l’effettiva comprensione del loro ruolo biologico potrà far luce sui possibili meccanismi di radio-resistenza, tendenza a recidivare del cordoma e allo sviluppo di agenti che possano avere come target il metabolismo dei ceramidi. Tali risultati dovrebbero essere validati in futuri studi clinici, in vitro e in vivo più ampi per confermare questo intricato legame tra il comportamento aggressivo del cordoma e dei ceramidi.
Introduction. Skull base chordomas are rare slow-growing neoplasms that arise from notochord. Their morbidity is mainly related to highly aggressive local invasion and resistance to treatments. Due to its heterogeneous appearance and not fully understood clinical and molecular behaviors, the main goal of the present work is to identify clinical and bio-molecular markers as specific prognostic factors that could be used for the management of skull base chordoma patients. Achieving a detailed prognostic signature of skull base chordomas is of paramount importance to personalize the treatment to each specific patient. Moreover, sphingolipids analysis is emerging as a new approach in many cancers and it has never been applied in chordomas. Our aim is to investigate chordoma biological behavior and the role of ceramides production in this context of proliferation and invasion. Patients and Methods. A retrospective review of all the patients diagnosed and treated for a skull base chordoma at the Fondazione IRCCS Istituto Neurologico “Carlo Besta” between January 1992 and December 2017 has been performed. Clinical, radiological, surgical and pathological data have been collected. A prospective collection of frozen surgical specimens has been performed to analyze ceramides species in chordomas. Sphingolipids were extracted from frozen tissues and total ceramides and dihydroceramides were evaluated by liquid chromatography and mass spectrometry. Survival analysis was performed according to Kaplan-Meier method. Univariate comparisons were conducted using Mann-Whitney, Chi-square and exact Fisher test. Simple linear regression and correlation with computation of Pearson coefficients analyses were conducted. Using a logistic regression model, statistically significant predictors were rated based on their odds ratios in order to build a personalized grading scale – the Peri-Operative Chordoma Scale (POCS). Results. Eighty-seven consecutive patients were surgically treated for a skull base chordoma during the period of recruitment. Seventy-eight patients were eligible for the retrospective review. There were 38 males (48.7%) and 40 females (51.3%). The mean follow-up was 69 months (range, 3–233). One-hundred-fourteen surgical operations were performed in the initial recruitment or recurrent setting. The presence of motor deficits in skull base chordoma revealed to be a significant prognostic factor correlating with a worse PFS (p=0.0480). Calcification on KM analysis showed a correlation with better outcomes (OS) compared with tumor lacking any calcification on CT scan (p value=0.0402). The degree of MR contrast enhancement revealed to be a significant and strong prognostic factor in terms of OS and PFS (p≤0.0001 and 0.0010, respectively). Jugular foramen involvement represented a significant prognostic factor with a worse PFS in the cohort of primary skull base chordomas (p=0.0130). The presence of chordoma in the pre-brainstem cistern revealed to be a significant prognostic factor with a worse PFS in the cohort of recurrent skull base chordomas (p=0.0210). Brainstem dislocation represented a significant prognostic factor correlating with a both worse outcome in terms of OS and PFS in the cohort of recurrent skull base chordomas (p=0.0060 and 0.0030). Extent of resection represents a strong prognostic factor according to PFS in the cohort of primary skull base chordomas (p=0.0200). Patients operated by an experienced chordoma surgeon did better in terms of prolonged PFS in the cohort of primary patients (p=0.0340). Development of post-operative complications in primary skull base chordoma patients represented an important prognostic factor related to both OS and PFS (p≤0.0001 and 0.0360, respectively). In the cohort of recurrent chordomas, ∆KPS correlated to both OS and PFS (p=0.0010 and 0.0180, respectively). Moreover, post-operative radiation treatment correlated with prolonged OS (p=0.0020) and PFS (p=0.0100). The following factors were found to be statistically significant predictors of both PFS and OS in the logistic regression model: MR contrast enhancement (intense vs mild/no), preoperative motor deficit (yes vs no) and the development of any post-operative complications (yes vs no). A grading scale was obtained with scores ranging between 0 and 17 (Nagelkerke’s pseudo R2=0.656). The mean total ceramides and dihydroceramides species in primary chordomas were 808.4±451.4 pmol/mg (522.5-1760.2) and 30.7±16.4 pmol/mg (17.6-62.4), respectively. The mean total ceramides and dihydroceramides species in recurrent chordomas were 1488.1±763.8 pmol/mg (540.7-2787.5) and 67.2±45.5 pmol/mg (9.0-145.6), respectively. Total ceramides species were significantly higher in recurrent chordomas that underwent previous surgical resection and radiation therapy in comparison to the primary chordomas (p=0.0496). The mean total ceramides and dihydroceramides species in “intense enhancement” group were 1597.6±737.8 pmol/mg (592.7-2787.5) and 69.1±45.0 pmol/mg (17.8-145.6), respectively. The mean total ceramides and dihydroceramides species in “no or mild enhancement” group were 664.7±120.4 pmol/mg (522.5-826.0) and 31.5±13.6 pmol/mg (17.6-53.6), respectively. Total ceramides and dihydroceramides were significantly higher in “intense enhancement” chordomas in comparison to the “no/mild enhancement” chordomas (p=0.0290 and p=0.0186, respectively). Analyzing the association between ceramides level and MIB-1 within each skull base chordoma patient, total ceramides level showed a strong association (r=0.7257, r2=0.5267) with MIB-1 staining (p=0.0033). Analyzing the association between DHCer level and MIB-1 within each skull base chordoma patient, total DHCer level showed also strong association (r=0.6733, r2= 0.4533) with MIB-1 staining (p= 0.0083). Among the single ceramides species Cer C24:1 (r=0.8814, r2=0.7769, p≤0.0001), DHCer C24:1 (r=0.8429, r2=0.7104, p=0.0002) and DHCer C18:0 (r=0.9426, r2=0.8885, p≤0.0001) levels showed a significant correlation with MIB-1 staining. Final candidate predictive factors that well fitted the regression model were: cer24:1 (r=0.824, p≤0.001), and DHCer C18:0 (r=0.748, p=0.002). Conclusion. Our clinical analysis showed that pre-operative clinical symptoms (motor and cranial nerve deficits), anatomical location (jugular foramen, pre-brainstem cisterns and brainstem dislocation), surgical features (extent of tumor resection and surgeon’s experience), development of post-operative complications and KPS decline represent significant prognostic factors. The degree of MR contrast enhancement significantly correlated to both OS and PFS. We also preliminarily developed the Peri-Operative Chordoma Scale (POCS) to aid the practitioner in the personalized management of patients undergoing potential adjuvant therapies. Our lipid analysis showed ceramides as promising tumoral bio-markers in skull base chordomas. Long and very long chain ceramides, such as Cer C24:1 and DHCer C24:1, may be related to a prolonged tumor survival, aggressiveness and the understanding of their effective biological role will hopefully shed lights on the mechanisms of chordoma radio-resistance, tendency to recur and use of agents targeting ceramide metabolism. Such results should be validated in future larger clinical, in-vitro and in-vivo studies to confirm such intricate link between ceramides and chordoma aggressive behavior.

INTRODUCCIÓN: El colgajo pericraneal (CP) ha sido habitualmente utilizado en las reconstrucciones cráneo faciales y de base de cráneo. Su utilidad en los abordajes abiertos se encuentra ampliamente descrita en la literatura. Sin embargo, el avance de las técnicas endoscópicas ha relegado el uso del CP por el de los colgajos endonasales. Al mismo tiempo, este avance representa una oportunidad para ampliar las indicaciones del CP a aquellos abordajes endoscópicos en los que los colgajos endonasales no se encuentren disponibles. OBJETIVO: Este trabajo tiene como objetivo estudiar y analizar el uso del CP en la reconstrucción endoscópica de base de cráneo y del septum nasal. MATERIALES Y MÉTODOS: Se realiza un estudio en tres áreas: 1. Se realiza un estudio anatómico en cadáver fresco en el que se ejecutan reconstrucciones de los distintos abordajes de base de cráneo (abordaje transcribiforme, abordaje transplanum, abordaje clival y abordaje de la unión cráneo-vetebral) y del septum nasal. En todos los especímenes, tras recrear el defecto que se a reconstruir, se realizar una disección clásica del CP y posteriormente se introduce a través de una osteotomía del seno frontal. Por último con un manejo endoscópico se realiza la reconstrucción del defecto. 2. En segundo lugar, se realiza un análisis radiológico en tomografías computerizadas (TC) de los límites de reconstrucción que permite el CP y la estandarización del tamaño del mismo según el defecto que se vaya a reconstruir. Se toma como referencia la pared posterior del conducto auditivo interno. 3. Posteriormente, se realiza un estudio clínico en pacientes con tumores de base de cráneo y perforación septal total en los que no existen opciones reconstructivas endonasales o estas no alcanzan el tamaño suficiente. En ellos, se realiza una reconstrucción endoscópica con CP de sus defectos. RESULTADOS: Las mediciones anatómicas mostraron que el tabique nasal tiene una longitud media de 5,8 ± 0,7 cm, mientras que el colgajo pericraneal presenta un promedio de 18,4 ± 1,3; 18,3 ± 1,3 cm de largo (área media 121,6 ± 17,7; 121,5 ± 19,4 cm2). En todos los especímenes se logró la reconstrucción total de los defectos. En el estudio radiológico, se determinó que para reconstruir defectos secundarios a abordajes transcribriforme, transtuberculum, clival y craneovertebrales, la incisión distal del colgajo pericraneal debe colocarse respectivamente a -3,7 ± 2,0 cm (ángulo -17,4 ± 8,5º), -0,2 ± 2,0 cm (ángulo -1,0 ± 9,3º), +5,5 ± 2,3 cm (ángulo +24,4 ± 9,7º), +8,4 ± 2,4 cm (ángulo +36,6 ± 11,5º), en relación con el punto de referencia. En el caso de la reconstrucción septal, las mediciones radiológicas revelaron que el área del colgajo pericraneal necesaria para reconstruir una perforación septal total sería de 40,9 ± 4,2 cm2, teniendo en cuenta un 30% adicional por la posible retracción durante la cicatrización. Para la reparación total del tabique, el borde distal del colgajo pericraneal debe situarse a 0,8 ± 2,0 cm (3,4 ± 8,78º) del punto de referencia (proyección vertical del canal auditivo externo). Los defectos de la base del cráneo (n = 6) y de la perforación septal total (n=1) en nuestra cohorte clínica se reconstruyeron completamente sin complicaciones. CONCLUSIONES: Este trabajo concluye que el CP presenta un área suficiente para la reconstrucción endoscópica de los distintos abordajes de base de cráneo y septal total. El uso del seno frontal como puerta de entrada a las fosa nasales y el manejo endoscópico del CP en las reconstrucciones es una técnica factible y simple.
The pericranial flap (PCF) has been commonly used in craneo-facial and skull base reconstructions. However, the advance of endoscopic techniques has relegated the use of PCF. At the same time, this advance represents an opportunity to extend the indications of the PCF to those endoscopic approaches in which the endonasal flaps are not available. The aims of this study is to analyze the use of the PCF in the endoscopic reconstruction of the skull base and the nasal septum. An anatomical study on fresh cadaver specimens in which reconstructions of the different skull base defects and nasal septum were carried out. The PCF was introduced through an osteotomy of the frontal sinus. Then, the defects were endoscopically repair. A radiological analysis in computed tomography was performed. The reconstruction limits allowed by the PCF and the standardization of the size of the PCF according to the defect were measured. A clinical study is performed in patients with tumors of the skull base and total septal perforation. In the anatomical study, the nasal septum length and the PCF length and area were obtained. In all the specimens, the total reconstruction of the defects was achieved. The radiological study determined that to reconstruct defects secondary to transcribriform, transtuberculum, clival and craniovertebral approaches, the distal incision of the PCF should be placed respectively at -3.7 ± 2.0 cm, -0,2 ± 2,0 cm, +5,5 ± 2,3 cm, +8,4 ± 2.4 cm, from the reference point (external auditory canal). For total repair of the septum, the distal edge of the PCF should be located 0.8 ± 2.0 cm from the reference point. Defects of the skull base (n = 6) and total septal perforation (n = 1) in our clinical cohort were completely reconstructed. This work concludes that the CP presents enough area for the endoscopic reconstruction of the different approaches of the skull base and total septal perforation. The use of the frontal sinus as the entrance and the endoscopic management of the CP in the reconstructions is a feasible and simple technique.

The existing paradigm of many surgical training programs continue to follow a timebased apprenticeship model where learning occurs serendipitously in the clinical environment. Recently, there have been several drivers for a change in this pedagogical ideology to one that is competency-based. These include concerns regarding the effect of training on patient safety and health economics, the implementation of work-hour restrictions, the advent of minimally invasive surgery and increase in post-training fellow appointments, which have all served to reduce the learning opportunities for surgical trainees. Thus, additional methods of training and assessing operative skills are required to bridge this gap. Not only has simulation-based training been demonstrated to improve technical skills, but the skills acquired have also been shown to be transferable to the operating theatre. Virtual reality simulators can do this through a high-fidelity, standardised and reproducible environment with the ability to deliver immediate objective feedback on performance. Feedback within the operating theatre is possible through the use of objective assessment tools that allow quantitative evaluations of operative performance. These can be used to identify weaknesses for deliberate practice. The laparoscopic appendicectomy (LA) is one of the most common emergency procedures conducted. Although frequently performed by trainees, LA is associated with a significant learning curve of between 20 to 30 cases, and often provides trainees with their first experiences of laparoscopic surgery. Despite this, little research in training and assessing skills for LA has been previously conducted. This thesis had two main aims. The first was to develop a proficiency-based technical skills training curriculum for LA surgery using a high-fidelity VR simulator. The second aim was to develop an evidence-based objective procedure-specific evaluation tool designed to assess technical performance during LA surgery. Prior to this, the need for such training and assessment tools was determined and used to guide their development by investigating the practice patterns of LA surgery in Australia. A population-based study demonstrated that there was a rapid increase in the utilisation of LA surgery in New South Wales between 2000 and 2010. This provided the initial evidence for the need for a method of training and assessing skills in LA surgery. Further evidence for this need was shown in a retrospective study of the practice patterns of LA surgery within a single tertiary centre, which found that surgical trainees had limited and selective learning opportunities, as well as longer operating times than experts. A survey of all General surgery trainees in Australia suggested that a proportion of these trainees had performed unsupervised LA surgery whilst still being on the documented learning curve. This has important implications regarding patient safety and further suggested a need for tools to train and assess skills in LA surgery. The most frequently used techniques and instruments were elicited from the surveyed trainees to guide the development of these tools. The first internationally applicable proficiency-based VR simulation curriculum to train technical skills in LA surgery was developed after demonstrating the face, content and construct validity of the LA modules on the LAP MentorTM VR simulator and obtaining benchmarks of expert performance. A Delphi methodology was then used to attain expert consensus regarding the steps and descriptors of “poor”, “average” and “excellent” performance at each of these steps. These were used to develop the first multiinstitutionally derived procedure-specific evaluation tool for LA surgery. This tool was then demonstrated to have high inter-rater and test-retest reliability, as well as construct and concurrent validity when objectively assessing intra-operative performance during LA surgery. The educational tools developed in this thesis not only bridges the gap created by the increasingly limited learning opportunities, but also provides an avenue for competency-based surgical training. Through the training of skills to proficiency using the curriculum developed in this thesis, surgical trainees can enter the operating theatre as a ‘pre-trained novice’ with an attenuated learning curve. They would then be ready to undergo supervised training in actual LA surgery with continual objective assessment and feedback using the procedure-specific evaluation tool we developed. This would allow a cycle of training and assessment, where specific strengths and weaknesses can be identified, practiced deliberately and re-assessed for improvement, until a defined level of competence in LA surgery is attained. Such a paradigm would represent a shift in the ideology of surgical training to one that focuses on the demonstration of competence and proficiency and, above all else, the optimisation of patient safety.

The endoscopic approach to the skull base has revolutionised surgery in this region. Neurosurgery involves working around anatomical structures that are uniquely sensitive to damage and manipulation and patients may be left with the potentially devastating consequences of violating these structures. The endoscope allows the surgeon to visualise and reach areas that were previously only accessible with large amounts of destructive dissection. Tumours are able to be removed and aneurysms clipped without the need for large craniotomies and bony drilling. There are, however, drawbacks. The midline endoscopic route takes the surgeon between the carotid arteries. It potentially violates the anterior communicating artery complex and the basilar artery region anterior to the brainstem. These are important arteries that supply critical structures. Damage to these, or diminution of blood flow through them, results in profound neurological dysfunction or death. The rate of damage to the carotid artery with these approaches ranges from 1.1-9% depending on the specific approach and pathology. The carotid artery in this region does not generally lend itself to suturing, clipping or direct closure methods. Currently, the gold standard for repair is the application of crushed muscle patch to stop the bleeding and seal the vessel. The drawbacks to this are that it takes time to harvest and control the bleed (generally requiring 2 surgeons), and that there is a risk of pseudoaneurysm formation post recovery. This thesis describes novel techniques that may replace the muscle patch in order that a single surgeon may have this technique available to them immediately. Aims: To demonstrate the use of fibrin/thrombin/gelatin patches, fibrin/thrombin glues, beta-chitosan patches and self-assembling peptides on a sheep model of carotid artery haemorrhage and quantify the rate of pseudoaneurysm formation. To show the percentage of platelets activated by crushed and uncrushed muscle, chitosan, and fibrin and thrombin patches and gels using flow cytometry to further delineate the mechanism of action of crushed muscle as a haemostatic agent. To quantify the stress response in surgeons training on this sheep vascular haemorrhage model de novo, to quantify its effect on surgeons’ teamwork and communication skills, and determine the effect and value of training on modulation of this stress response.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 2018

abstract: During the past five decades neurosurgery has made great progress, with marked improvements in patient outcomes. These noticeable improvements of morbidity and mortality can be attributed to the advances in innovative technologies used in neurosurgery. Cutting-edge technologies are essential in most neurosurgical procedures, and there is no doubt that neurosurgery has become heavily technology dependent. With the introduction of any new modalities, surgeons must adapt, train, and become thoroughly familiar with the capabilities and the extent of application of these new innovations. Within the past decade, endoscopy has become more widely used in neurosurgery, and this newly adopted technology is being recognized as the new minimally invasive future of neurosurgery. The use of endoscopy has allowed neurosurgeons to overcome common challenges, such as limited illumination and visualization in a very narrow surgical corridor; however, it introduces other challenges, such as instrument "sword fighting" and limited maneuverability (surgical freedom). The newly introduced concept of surgical freedom is very essential in surgical planning and approach selection and can play a role in determining outcome of the procedure, since limited surgical freedom can cause fatigue or limit the extent of lesion resection. In my thesis, we develop a consistent objective methodology to quantify and evaluate surgical freedom, which has been previously evaluated subjectively, and apply this model to the analysis of various endoscopic techniques. This model is crucial for evaluating different endoscopic surgical approaches before they are applied in a clinical setting, for identifying surgical maneuvers that can improve surgical freedom, and for developing endoscopic training simulators that accurately model the surgical freedom of various approaches. Quantifying the extent of endoscopic surgical freedom will also provide developers with valuable data that will help them design improved endoscopes and endoscopic instrumentation.
Dissertation/Thesis
Ph.D. Neuroscience 2014

碩士
臺中健康暨管理學院
健康管理研究所
93
Objective: The aim of this study was to evaluate the relative costs of benign skull base tumors treated with open surgery and gamma knife radiosurgery. Materials and Methods: In a retrospective study in China Medical University Hospital, we studied 174 patients with benign skull base tumors, less than 3 cm in diameter (or volume less than 30 ml), admitted in the past 4 years. Group A (n=94) underwent open surgery for removal of the tumors while group B (n=80) underwent gamma knife radiosurgery. The total costs were evaluated by both direct and indirect cost. The direct costs comprised intensive care unit (ICU) cost, ward cost, operating room (OR) cost, and outpatient visiting cost. The indirect costs included workless cost and mortality cost. The length of hospital stay, the length of workless day, surgical complications, mortality, and cost-effectiveness were calculated too. Student t-test and Chi-square test were employed for statistical analysis. Results: The mean length of hospital stay for open surgery was 18.2 ±30.4 days including 5.0 ±14.7 days of ICU stay and 13.0 ±15.2 days of ward stay. The mean hospital stay for gamma knife was 2.2 ±0.9 days with no need of ICU stay, (open surgery vs. gamma knife, P<0.01). The mean workless day for open surgery was 119 ±142 days and 7.6 ±6.4 days for gamma knife, (open surgery vs. gamma knife, P<0.01). The gamma knife cost per hour (1,435 USD) is higher than the open surgery cost per hour (450 USD), P<0.01. The direct cost for gamma knife (9,460 ±6,691 USD) is higher than that for open surgery (5,530 ±5,597 USD), P<0.01. The hospital benefit was more of a negative balance for gamma knife (-4,830 ±4,263 USD) than for open surgery (-960 ± 5,325 USD), P<0.05. Open surgery had more complication rates (31.2%) than gamma knife (3.8%). Open surgery had a mortality rate of 5.3%; there was no mortality for gamma knife. The indirect costs, including workless cost and mortality cost, were significantly higher for open surgery than for gamma knife, P<0.01. Finally, the total cost (9,812 ±6,981 USD) is higher for open surgery than for gamma knife (23,338 ±95,253 USD), P<0.01. The cost-effectiveness for gamma knife (15 USD/day) is better than for open surgery (44 USD/day), P<0.01. It is pretty meaningful when the cost-effectiveness of socioeconomic cost for gamma knife (15 USD/day) is lower than the cost of working day (36.5 USD/day of our GDP). Conclusions: Most of the costs loss with open surgery for benign skull base tumors comes from the indirect costs of workless days and mortality loss. Gamma knife radiosurgery is still a worthwhile treatment to our patients and to our society because it may shorten hospital stays and workless days and reduce complications, mortality, socio-economic loss, and achieve better cost-effectiveness.

Facial Artery Musculomucosal Flap in Skull Base Reconstruction Xie L. MD, Lavigne F. MD, Rahal A. MD, Moubayed SP MD, Ayad T. MD Introduction: Failure in skull base defects reconstruction can have serious consequences such as meningitis and pneumocephalus. The nasoseptal flap is usually the first choice but alternatives are necessary when this flap is not available. The facial artery musculomucosal (FAMM) flap has proven to be successful in head and neck reconstruction but it has never been reported in skull base reconstruction. Objective: To show that the FAMM flap can reach some key areas of the skull base and be considered as a new alternative in skull base defects reconstruction. Methods: We conducted a cadaveric study with harvest of modified FAMM flaps, endoscopic skull base dissection and maxillectomies in 13 specimens. Measures were taken for each harvested FAMM flap. Results: The approximate mean area for reconstruction from the combination of the distal FAMM and the extension flaps is 15.90 cm2. The flaps successfully covered the simulated defects of the frontal sinus, the ethmoid areas, the planum sphenoidale, and the sella turcica. Conclusion: The FAMM flap can be considered as a new alternative in the reconstruction of skull base defects. Modifications add extra length to the traditional FAMM flap and can contribute to a tighter seal of the defect as opposed to the FAMM flap alone.
Le lambeau musculomuqueux de la joue dans la reconstruction de la base du crâne Xie L. MD, Lavigne F. MD, Rahal A. MD, Moubayed SP MD, Ayad T. MD Introduction: Un échec dans la reconstruction de la base du crâne peut avoir des conséquences graves telles que la méningite ou la pneumocéphalie. Le premier choix de la reconstruction est le lambeau nasoseptal. Lorsque ce dernier n’est pas disponible, d’autres alternatives sont nécessaires. Le lambeau musculomuqueux de la joue (FAMM) a une place établie dans la reconstruction des déficits de la tête et du cou, mais il n’a pas jamais été décrit dans la reconstruction de la base du crâne. Objectif: Démontrer que le lambeau de FAMM peut atteindre des zones clés de la base du crâne et être considéré comme une nouvelle option de reconstruction de cette région. Méthode: Nous avons entrepris une étude cadavérique avec prélèvement de lambeaux de FAMM modifiés et une dissection endoscopique de la base du crâne sur 13 spécimens. Des mesures ont été prises pour chaque lambeau prélevé. Résultats: L’aire de reconstruction moyenne du lambeau de FAMM et des extensions est de 15.90 cm2. Les lambeaux couvrent totalement les déficits simulés du sinus frontal, des ethmoïdes, le toit du sphénoïde et la selle turcique. Conclusion: Le lambeau de FAMM peut être considéré comme une nouvelle alternative dans la reconstruction des déficits de la base du crâne. Les modifications apportent une longueur additionnelle et contribuent à une couverture plus étanche du déficit que le lambeau de FAMM seul.

Background and Aim: „CI-Wizard“ is a new, three-dimensional software planning tool for cochlear implant surgery with manual and semi-automatic algorithms to visualize anatomical risk structures of the lateral skull base preoperatively. Primary endpoints of the study represented the evaluation of the CI Wizards usability, accuracy, subjectively perceived and objectively measured time in clinical practice. Materials and Methods: In a period from January 2014 to March 2015, n=36 participants were included in this study. These members were divided into three groups of equal number (n=12), but different level of experience. Senior doctors and consultants (group 1), residents (group 2) and medical students (group 3) segmented twelve different CT-scan data sets of the CI Wizard (four per participant). In total, n=144 data sets were collected. The usability of the CI Wizard was measured by the given questionnaire with an interval rating scale. The Jaccard coefficient (JT) was used to evaluate the accuracy of the anatomical structures segmented. The subjectively-perceived time was measured with an interval rating scale in the questionnaire and was compared with the objectively mean measured time (time interact). Results: Across all three groups, the usability of the CI Wizard has been assessed between 1 ('very good') and 2 ('with small defects'). Subjectively, the time was stated as 'appropriate' by questionnaire. Objective measurements of the required duration revealed averages of n=9.8 minutes for creating a target view. Concerning the accuracy, semi automatic anatomical structures such as the external acoustic canal (JT=0.90), the tympanic cavity (JT=0.87), the ossicles (JT=0.63), the cochlea (JT=0.66) and the semicircular canals (JT=0.61) reached high Jaccard values, which describes a great match of the segmented structures between the partcipants and the gold standard. Facial nerve (JT=0.39) and round window (JT=0.37) reached lower Jaccard values. Very little overlap tendency was found for the chorda tympani (JT=0.11). Conclusion: This software program represents a further important step in the development of pre-operative planning tools in cochlear implant surgery. The study revealed a high level of satisfaction in the usability. The subjectively required time was considered as „appropriate“ and the objectively mean measured time was n=9.8 minutes short enough, so that a clinical application seems realistic. Particularly for semi-automatically segmented structures, it represented a good accuracy. For purely manual segmented structures, further improvements are desirable. Finally, this program also provides a good learning tool for medical students and residents to become familiar with the anatomy of the lateral skull base.:1 Einführung 1 1.1 Cochlea Implantate (CI) 1 1.2 Bildverarbeitungsprogamme zur präoperativen Planung eines Cochlea Implantates 2 1.2.1 Segmentierung in der Medizin 2 1.2.2 CI-Wizard 4 1.3 Fragebogen 6 1.4 Zielsetzung 6 1.5 Zusammenfassung der Ergebnisse 7 2 Publikation 8 3 Zusammenfassung 19 4 Literaturverzeichnis 23 Anlagen 26 Beitrag der Promovendin bei geteilter Erstautorenschaft 34 Erklärung über die eigenständige Abfassung der Arbeit 35 Lebenslauf 36 Danksagung 37