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Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used either alone or in combination with different approaches when dealing with the pathologies of the skull base. The objective of the current study is to evaluate the surgical anatomy of transorbital endoscopic approaches by cadaver dissections as well as providing objective clinical data on their actual employment and morbidity through a systematic review of the current literature. Four cadaveric specimens were dissected, and step-by-step dissection of each endoscopic transorbital approach was performed to identify the main anatomic landmarks and corridors. A systematic review with pooled analysis of the current literature from January 2000 to April 2020 was performed and the related studies were analyzed. Main anatomical landmarks are presented based on the anatomical study and systematic review of the literature. With emphasis on the specific transorbital approach used, indications, surgical technique, and complications are reviewed through the systematic review of 42 studies (19 in vivo and 23 anatomical dissections) including 193 patients. In conclusion, transorbital endoscopic approaches are promising and appear as feasible techniques for the surgical treatment of skull base lesions. Surgical anatomy of transorbital endoscopic approaches can be mastered through knowledge of a number of anatomical landmarks. Based on data available in the literature, transorbital endoscopic approaches represent an important complementary that should be included in the armamentarium of a skull base team.

BACKGROUND: The spheno-orbital region (SOR) is a complex anatomic area that can be accessed with different surgical approaches. OBJECTIVE: To quantitatively compare, in a preclinical setting, microsurgical transcranial approaches (MTAs), endoscopic endonasal transpterygoid approach (EEA), and endoscopic transorbital approaches (ETOAs) to the SOR. METHODS: These approaches were performed in 5 specimens: EEA, ETOAs (superior eyelid and inferolateral), anterolateral MTAs (supraorbital, minipterional, pterional, pterional-transzygomatic, and frontotemporal-orbitozygomatic), and lateral MTAs (subtemporal and subtemporal transzygomatic). All specimens underwent high-resolution computed tomography; an optic neuronavigation system with dedicated software was used to quantify working volume and exposed area for each approach. Mixed linear models with random intercepts were used for statistical analyses. RESULTS: Anterolateral MTAs offer a direct route to the greater wings (GWs) and lesser wings (LWs); only they guarantee exposure of the anterior clinoid. Lateral MTAs provide access to a large area corresponding to the GW, up to the superior orbital fissure (SOF) anteriorly and the foramen rotundum medially. ETOAs also access the GW, close to the lateral portion of SOF, but with a different angle of view as compared to lateral MTAs. Access to deep and medial structures, such as the lamina papyracea and the medial SOF, is offered only by EEA, which exposes the LW and GW only to a limited extent. CONCLUSION: This is the first study that offers a quantitative comparison of the most used approaches to SOR. A detailed knowledge of their advantages and limitations is paramount to choose the ideal one, or their combination, in the clinical setting.

In Italy, recent legislation (Law No. 10/2020) has tuned regulations concerning the donation of one's postmortem body and tissues for study, training, and scientific research purposes. This study discusses several specific issues to optimise the applicability and effectiveness of such an important, novel regulatory setting. Critical issues arise concerning the learners, the type of training and teaching activities that can be planned, the position of academic anatomy institutes, the role of family members in the donation process, the time frame of the donation process, the eligibility of partial donation, or the simultaneous donation of organs and tissues to patients awaiting transplantation. In particular, a universal time limit for donations (i.e., one year) makes it impossible to plan the long-term use of specific body parts, which could be effectively preserved for the advanced teaching and training of medical students and surgeons. The abovementioned conditions lead to the limited use of corpses, thus resulting in the inefficiency of the whole system of body donation. Overall, the donors’ scope for the donation of their body could be best honoured by a more flexible and tuneable approach that can be used on a case-by-case basis. Furthermore, it is deemed necessary to closely monitor the events scheduled for corpses in public nonacademic institutions or private enterprises. This paper presents useful insights from Italian anatomists with the hope of providing inspiration for drafting the regulations. In conclusion, this paper focuses on the critical issues derived from the recently introduced Italian law on the donation and use of the body after death and provides suggestions to lawmakers for future implementations.

Background: Endoscopic transnasal transclival intradural surgery is limited by a high postoperative cerebrospinal fluid leak rate. The aim of this study was to investigate the role of three-dimensional printing to create a personalized, rigid scaffold for clival reconstruction. Methods: Two different types of clivectomy were performed in 5 specimens with the aid of neuronavigation, and 11 clival reconstructions were simulated. They were repaired with polylactide, three-dimensional–printed scaffolds that were manually designed in a computer-aided environment based either on the real or on the predicted defect. Scaffolds were printed with a fused filament fabrication technique and different offsets. They were positioned and fixed either following the gasket seal technique or with screws. Postdissection radiological evaluation of scaffold position was performed in all cases. In 3 specimens, the cerebrospinal fluid leak pressure point was measured immediately after reconstruction. Results: The production process took approximately 30 hours. The designed scaffolds were satisfactory when no offset was added. Wings were added during the design to allow for screw positioning, but broke in 30% of cases. Radiological assessment documented maximal accuracy of scaffold positioning when the scaffold was created on the real defect; accuracy was satisfactory when the predicted clivectomy was performed under neuronavigation guidance. The cerebrospinal fluid leak pressure point was significantly higher when the scaffold was fixed with screws compared with the gasket technique. Conclusions: In this preclinical setting, additive manufacturing allows the creation of customized scaffolds that are effective in reconstructing even large and geometrically complex clival defects.

Background: Achieving an effective endoscopic skull base reconstruction in case of large dural defects requires specific training and can be extremely challenging. The aim of this study was to describe the development and validation of a preclinical model for cerebrospinal fluid (CSF) leak repair, which can be used for training and to test the mechanical efficacy of endoscopic skull base reconstruction. Methods: Eleven fresh-frozen cadaver heads were dissected. A catheter was inserted in the subdural space via a cervical access, which was sealed with mastic; a vertical graduated tube connected to the catheter measured intracranial pressure (ICP), while stained water was injected intracranially. After endoscopic skull base reconstruction was performed, an expert surgeon assessed its efficacy. ICP was then gradually increased until a leak was evident and CSF leak pressure value was recorded. The correlation between subjective and quantitative evaluations was investigated through Pearson and Spearman correlation tests. Results: The model was successfully tested in 11 specimens. A single, large dural defect was created in each model (transplanum-transtuberculum = 4; transplanum-transtuberculum-transsellar = 3; transclival = 3; transcribriform-transplanum = 1). Skull base reconstruction always comprised a rigid buttress with temporal fascia and/or fat. The CSF leak pressure ranged from 4 to 110 cmH2O. The correlation between expert subjective and quantitative assessment of skull base reconstruction mechanical efficacy was high (r = 0.7; rs = 0.7; p = 0.010 and p = 0.006, respectively). Conclusion: This preclinical model is simple, easily reproducible, and effective in simulating an intraoperative leak and objectively measures the CSF leak pressure point of a skull base reconstruction.

Background and objective: The clivus was defined as “no man’s land” in the early 1990s, but since then, multiple approaches have been described to access it. This study is aimed at quantitatively comparing endoscopic transnasal and microsurgical transcranial approaches to the clivus in a preclinical setting, using a recently developed research method. Methods: Multiple approaches were performed in 5 head and neck specimens that underwent high-resolution computed tomography (CT): endoscopic transnasal (transclival, with hypophysiopexy and with far-medial extension), microsurgical anterolateral (supraorbital, mini-pterional, pterional, pterional transzygomatic, fronto-temporal-orbito-zygomatic), lateral (subtemporal and subtemporal transzygomatic), and posterolateral (retrosigmoid, far-lateral, retrolabyrinthine, translabyrinthine, and transcochlear). An optic neuronavigation system and dedicated software were used to quantify the working volume of each approach and calculate the exposure of different clival regions. Mixed linear models with random intersections were used for statistical analyses. Results: Endoscopic transnasal approaches showed higher working volume and larger exposure compared with microsurgical transcranial approaches. Increased exposure of the upper clivus was achieved by the transnasal endoscopic transclival approach with intradural hypophysiopexy. Anterolateral microsurgical transcranial approaches provided a direct route to the anterior surface of the posterior clinoid process. The transnasal endoscopic approach with far-medial extension ensured a statistically larger exposure of jugular tubercles as compared with other approaches. Presigmoid approaches provided a relatively limited exposure of the ipsilateral clivus, which increased in proportion to their invasiveness. Conclusions: This is the first anatomical study that quantitatively compares in a holistic way exposure and working volumes offered by the most used modern approaches to the cli

Objective: To quantitatively compare different microsurgical and endoscopic approaches to the middle cranial fossa in a preclinical setting with a novel, computer-based research method. Methods: Different approaches were performed bilaterally in 5 head and neck specimens that underwent high-resolution computed tomography scans: 5 transcranial anterolateral (supraorbital, mini-pterional, pterional, pterional-transzygomatic, fronto-temporal-orbito-zygomatic) without and with anterior clinoidectomy; 2 transcranial lateral (subtemporal and subtemporal-transzygomatic); 2 endoscopic transnasal (transpterygoid, transpterygoid to infratemporal fossa); 2 endoscopic transorbital (superior eyelid and inferolateral), and endoscopic transmaxillary. A dedicated navigation system was used to quantify surgical working volumes and exposure of different areas of the middle cranial fossa (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Statistical analysis was performed using a mixed linear model with bootstrap resampling. Results: Endoscopic transnasal and fronto-temporal-orbito-zygomatic approaches with anterior clinoidectomy showed the largest surgical volumes. Endoscopic approaches allowed a wider exposure of medial anatomical surfaces (e.g., the petrous apex) compared with transcranial ones. Transcranial approaches with larger craniotomies allowed the widest exposure of superomedial anatomical structures (e.g., roof of cavernous sinus). The resection of the zygomatic arch allowed exposure of more medial surfaces with an inferior to superior trajectory. Conclusions: This study implemented a novel neuronavigation-based research method to quantitatively compare different approaches to the middle cranial fossa; its results might guide, after consideration of clinical implications, the choice of the neurosurgical approach to different areas of this complex skull base region.

Bone marrow and adipose tissue human mesenchymal stem cells were seeded in highly performing 3D gelatin–chitosan hybrid hydrogels of varying chitosan content in the presence of human platelet lysate and evaluated for their proliferation and osteogenic differentiation. Both bone marrow and adipose tissue human mesenchymal stem cells in gelatin–chitosan hybrid hydrogel 1 (chitosan content 8.1%) or gelatin–chitosan hybrid hydrogel 2 (chitosan 14.9%) showed high levels of viability (80%–90%), and their proliferation and osteogenic differentiation was significantly higher with human platelet lysate compared to fetal bovine serum, particularly in gelatin–chitosan hybrid hydrogel 1. Mineralization was detected early, after 21 days of culture, when human platelet lysate was used in the presence of osteogenic stimuli. Proteomic characterization of human platelet lysate highlighted 59 proteins mainly involved in functions related to cell adhesion, cellular repairing mechanisms, and regulation of cell differentiation. In conclusion, the combination of our gelatin–chitosan hybrid hydrogels with hPL represents a promising strategy for bone regenerative medicine using human mesenchymal stem cells.

Background: Several surgical approaches to the parapharyngeal space (PPS) have been proposed. An objective description of advantages and limitations of the surgical routes is lacking. Methods: Ten cadaver heads were dissected using the transnasal (medial, lateral), sublabial, transoral (transpharyngeal, transvestibular, transmandibular), transcervical (transcervical, transparotid, transmandibular, transmastoid), and type C and D infratemporal approaches. Neurovascular and musculoskeletal structures encountered were analyzed. A navigation-based quantification of working volume and exposure of PPS compartments was accomplished. Results: Transnasal approaches exposed the upper PPS, though with limited working volume. Transoral approaches exposed the middle PPS, minimizing neurovascular structures crossed. Only transcervical and skull base approaches exposed the entire PPS, crossing several neurovascular structures. Conclusion: A tentative systematization of the surgical approach(es) to PPS in relation to different targets is provided: unicompartmental resection can be performed with a single, conservative access, whereas multicompartmental dissections frequently require a wider or multiportal approach.

Robotics has already been applied to several surgical fields, but only transoral robotic surgery has a recognized role in skull base surgery. Different preclinical prototypes have been described for endoscopic transnasal skull base surgery (ESBS), but only recently a dedicated, hybrid robotic system has become available for clinical practice.This chapter reviews the use of holders in neurosurgery and skull base surgery, provides an overview of limitations of previous robotic systems that were designed for other surgical applications, describes the different preclinical robotic prototypes that have been developed for ESBS, and reports the initial preclinical and clinical experience with a novel, dedicated, hybrid robotic solution for endoscopic skull base surgery (EndoscopeRobot®, Medineering, Munich, Germany).The era of robotics in skull base surgery is at its dawn, but advantages of the hybrid solution are already evident, though further studies are needed to gain additional data.

Background: The armamentarium for anterior skull base (ASB) reconstruction includes a variegate spectrum of grafts, endonasal pedicled flaps, regional pedicled flaps, and free flaps, which are selected to face specific scenarios. The use of a vascularized flap in case of large ABS defects ensures an adequate blood supply. The aim of this study was to evaluate the possible role of temporoparietal fascia flap (TPFF) in ASB reconstruction. Methods: Eight fresh-frozen head specimens were dissected to evaluate the adequacy of TPFF and pericranial flap (PF) for the reconstruction of ASB defects. The percentage of coverage of the ASB was calculated for TPFF and PF. An anatomic-radiologic analysis was performed to provide useful practical information for flap harvesting and positioning. Results: The TPFF was easily transposed to the ABS defect through an epidural corridor; the edges of the TPFF were successfully placed in the intradural space, in the epidural space, or on the extracranial surface of the ABS defect. The PF was particularly adequate for median defects, and the TPFF was shown to be useful also in cases with paramedian-supraorbital extension. The median percentage of coverage of the ASB was significantly higher for TPFF (85.1%) than PF (65.7%) (P = 0.018). Conclusions: The supraorbital epidural corridor is a possible novel pathway for transposition of the TPFF for ASB reconstruction. Side-door TPFF was shown to be an ideal choice for large ASB defect with lateral supraorbital extension and could be useful in the scenario of salvage reconstruction for recurrent ABS cerebrospinal fluid leak.

Background: Transnasal endoscopic approaches to the clivus have been established recently. Comparative analyses with classic lateral approaches are limited. In this study, we compared transnasal endoscopic and lateral approaches to the clivus, quantifying the exposure and working volume of each approach in the anatomy laboratory. Methods: High-resolution computed tomography scans were performed on 5 injected specimens (10 sides). In each specimen, transnasal endoscopic approaches (i.e., paraseptal, transrostral, extended transrostral, transethmoidal, and extended transclival without and with intradural hypophysiopexy) and lateral approaches (i.e., retrosigmoid, far-lateral, presigmoid retrolabyrinthine and translabyrinthine) to the clivus were performed. An optic neuronavigation system and dedicated software (ApproachViewer; Guided Therapeutics Program, University Health Network, Toronto, Ontario, Canada) were used to quantify the working volume and exposed clival area of each approach. Statistical evaluation was performed with the Kruskal–Wallis test and Steel–Dwass–Critchlow–Fligner post hoc test. Results: Endoscopic transnasal transclival approaches showed higher working volume and larger clival exposure compared with lateral approaches. Incremental volumetric values were evident for transnasal approaches; presigmoid approaches provided less working volume than retrosigmoid approaches. A transnasal transclival approach with hypophysiopexy provided significant exposure of the upper clivus (84.4%). The transrostral approach was the first transnasal approach providing satisfactory access to the midclivus (66%); retrosigmoid and far-lateral approaches provided exposure of approximately one half of the midclivus. The lower clivus was optimally exposed with endoscopic transclival approaches (83%), whereas access to this region was limited with lateral approaches. Conclusions: This quantitative anatomic study shows that endoscopic transnasal approaches to the clivus pro

Background Endoscopic visualization does not necessarily correspond to an adequate working space. The need for balancing invasiveness and adequacy of sellar tumor exposure has recently led to the description of multiple endoscopic endonasal transsphenoidal approaches. Comparative anatomic data on these variants are lacking. Object We sought to quantitatively compare endoscopic endonasal transsphenoidal approaches to the sella and parasellar region, using the concept of “surgical pyramid.” Methods Four endoscopic transsphenoidal approaches were performed in 10 injected specimens: 1) hemisphenoidotomy; 2) transrostral; 3) extended transrostral (with superior turbinectomy); and 4) extended transrostral with posterior ethmoidectomy. ApproachViewer software (part of GTx-Eyes II, University Health Network, Toronto, Canada) with a dedicated navigation system was used to quantify the surgical pyramid volume, as well as exposure of sellar and parasellar areas. Statistical analyses were performed with Friedman's tests and Nemenyi's procedure. Results Hemisphenoidotomy provided limited exposure of the sellar area and a small working volume. A transrostral approach was necessary to expose the entire sella. Exposure of lateral parasellar areas required superior turbinectomy or posterior ethmoidectomy. The differences between each of the modules was statistically significant. Conclusion The present study validates, from an anatomic point of view, a modular classification of endoscopic endonasal transsphenoidal approaches to the sellar region.

Background: Endoscopic medial maxillectomies (EMMs) are used to optimize exposure of the maxillary sinus and retromaxillary areas. Although in type D EMM (Sturmann-Canfield procedure) the anterior superior alveolar nerve (ASAN) is always at risk of injury, only 29% of patients complained of alveolar process and dental anesthesia. The purpose of this anatomical study is to assess the neural anastomotic network of the ASAN (ASAN-NAN) and describe different extensions of type D EMMs in a preclinical setting. Methods: The ASAN and its medial anastomotic branches (MABs) and lateral anastomotic branches (LABs) were evaluated by cone-beam computerized tomography (CBCT). Five different extensions of type D (D1 to D5) EMMs were identified and nerves at risk of injury in each type were assessed by CBCT. Moreover, quantification of surgical corridors was performed on cadaver heads with a neuronavigation system. Results: Fifty-seven CBCT scans were analyzed. The ASAN would be spared in 16.3% of cases with a type D1 EMM, while it would be injured in the majority of type D2 to D5 resections. At least 1 nerve of the ASAN-NAN was spared in 96.6%, 93%, 74.6%, 0%, and 65.8% of type D1 to D5 EMMs, respectively. Two cadaver heads were dissected and the incremental volume and number of maxillary subsites exposed was assessed in type D1 to D5 EMMs. Conclusion: ASAN function impairment is probably compensated by LABs and MABs. If this hypothesis will be validated in a prospective study on patients, preoperative CBCT evaluation could predict neurological morbidity after type D EMM, and allow tailoring the procedure to minimize impairment of the ASAN-NAN.

Background The nomenclature adopted for endoscopic medial maxillectomies (EMMs) is exceedingly heterogeneous. The aim of this study was to objectively measure surgical exposure in a preclinical anatomic setting to validate a classification for modular EMMs. Materials and Methods Computed tomography was used to scan 6 cadaver heads, and images were uploaded on dedicated software. A neuronavigation system was used to measure areas and volumes of surgical corridors during dissection. Differences of >10% of area exposed and >3 cm3 of volume were considered to define incremental types of EMM. Specific anatomic targets were assessed on the axial and sagittal planes. Influence of anatomic variants on surgical exposure was evaluated. Results There were 4 types of EMMs (A–D), with a transseptal variant for each, identified. In the axial plane, type A exposed the vidian canal and foramen rotundum, type B exposed the foramen ovale and foramen spinosum, and transseptal type C or type D exposed the coronoid process. In the sagittal plane, type A exposed the vidian canal, and type B exposed the foramen ovale and styloid process. Transseptal type C exposed the pterygomaxillary fissure, and type D exposed the inferior border of the lateral pterygoid plate. The nasal floor limits the downward angle in transseptal approaches. The width of the piriform aperture independently influenced surgical volume of types B and C. Conclusions This modular classification of EMMs, based on quantitative analysis in a preclinical setting, should allow for better personalized preoperative surgical planning and provides standardization of nomenclature.

The ophthalmic artery has an anomalous origin in 2–3 % of cases and rarely arises from the anterior cerebral artery. Herein, we provide the first anatomical, radiological, and histological description of such an anomalous origin, together with a literature review. During the anatomical dissection of an 81-year-old Caucasian male, the absence of the right ophthalmic artery in its usual location was evident from an endonasal transsphenoidal perspective. The specimen was then studied in detail, through multiple dissections, corrosion casting, high-resolution CT, and histological analysis. The English literature on anomalous origins of the ophthalmic artery was reviewed, together with reported associated pathologies. Anatomo-radiological analysis documented that the right ophthalmic artery arose from the inferior surface of A1 tract of the anterior cerebral artery (A1) and passed over the optic nerve in its subarachnoid tract. A meningo-ophthalmic artery was evident on the same side and reached the orbit through the superior orbital fissure. Histological examination of both internal carotid artery (ICA) walls documented a significantly decreased thickness of the tunica media and adventitia on the side of the anomalous ophthalmic artery, with a significantly different content of collagen types I and III. The literature review documented an association of aneurysms and anomalous ophthalmic arteries. To the best of our knowledge, this is the first anatomical report that includes a radiological and arterial wall analysis of a persistent ventral ophthalmic artery. The latter provides histological data that support the clinical evidence of a higher association of aneurysms with anomalous origins of the ophthalmic artery.

Background: In recent years, transorbital endoscopic approaches are increasing in popularity as they provide several corridors to reach lateral areas of the ventral skull base through the orbit. The aim of this study is to investigate the feasibility of the inferolateral transorbital endoscopic approach (ILTEA) by detailing the step-by-step dissection, anatomic landmarks, and target anatomic areas. Methods: Seven cadaveric specimens (14 sides) were dissected in the Laboratory of Endoscopic Anatomy of the University of Brescia. Step-by-step dissection of ILTEA was performed to identify the main anatomic landmarks and corridors. Skin incision, dural incision, and boundaries of craniectomy were measured. Neuronavigation was used to check landmarks, track boundaries of surgical volumes, and measure orbital dislocation. Results: The study on the 14 ILTEAs defined 1 anatomic area ("waterline door") that leads to 4 corridors: Meckel's cave corridor, carotid foramen corridor, petrous corridor, and transdural middle fossa corridor. Crucial anatomic landmarks were identified and analyzed. Orbital dislocation was <10 mm. Conclusions: ILTEA provides the surgeon with a direct route to the region of the "waterline door," lateral areas of the ventral skull base, and middle cranial fossa. In addition, it allows an optimal view of the intracranial and extracranial portions of the maxillary and mandibular nerves. Further anatomic and clinical studies are needed to validate ILTEA in surgical practice.

Background Several endoscopic landmarks for the internal carotid artery (ICA) have been identified, but they have always been proposed in a “static” perspective. The aim of this study was to investigate how the surgical corridor and optical distortion can influence the perception of carotid landmarks in transnasal endoscopic surgery. Methods Computed tomography images of skulls in 20 subjects were analyzed. The petrous carotid angle (PCA) was calculated as the angle between the petrous carotid axis and the coronal plane connecting stylomastoid foramina. The angle of incidence (AI) on the anterior carotid genu of 3 different surgical corridors (contralateral nostril, ipsilateral nostril, and transmaxillary ipsilateral route) was evaluated. PCA, AI, and their differences were studied by Spearman's correlation test. Two cadaver heads were dissected, simulating the studied surgical corridors. The fish-eye effect was empirically quantified. Results Mean PCA was 31° (range, 21–41°). PCA and AI are linked by an inverse proportion relationship. A transmaxillary approach always ensures the highest value of AI on the target. The cadaveric dissection qualitatively confirmed the radiologic data. The fish-eye effect can cause a compression of distance perception as high as 37%. Conclusions The surgical corridor and endoscope optic distortion can influence ICA visualization and the perception of its anatomic landmarks. In a 2-nostril, 4-handed approach, it is advisable to place the endoscope and instrument for dissection in the nostril that is ipsilateral to the lesion. Awareness of the different perspectives and related optical distortions is essential when working in proximity to the ICA.