Defining the Safe Zone; the Endoscopic Sublabial Transmaxillary Approach to the Middle Cranial Fossa

Defining the Safe Zone; the Endoscopic Sublabial Transmaxillary Approach to the Middle Cranial Fossa | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Defining the Safe Zone; the Endoscopic Sublabial Transmaxillary Approach to the Middle Cranial Fossa Ebubekir Akpınar, Aysu İyigün Kabakcı, Hasan Çağrı Postuk, Ercan Boşnak, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6795600/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Almost all approaches to middle cranial fossa pathologies are performed with transcranial approaches. Studies on the endoscopic approach to this region are gaining popularity over time. In this study, we aimed to demonstrate the anatomical framework of the endoscopic transmaxillary transpterygoidal approach to the middle cranial fossa (ETTAMCF). Method Six formalin fixed red and blue silicon injected human cadaveric heads were used for endoscopic dissections to define surgical landmarks and limits of the ETTAMCF. Photos were taken with 4K high-definition camera and video monitor endoscopy systems. Results To reach middle cranial fossa via ETTAMCF includes; A bucco-gingival sulcus insicion, mucosal dissection, drilling maxillary sinus anterior wall (limited superiorly with infraorbital foramen, inferiorly with buccogingival sulcus), removing mucosa of maxillary sinus while preserving infraorbital nerve, opening posterior wall of the maxillary sinus (limited medialy with infraorbital nerve), drilling pterygoid process, mobilize and retracting the upper head of lateral pterygoid muscle and temporal muscle, definition foramen rotundum and foramen ovale with following maxillary nerve and mandibular nerve, drilling sphenoid bone (limited medially with vertical line from foramen ovale inferiorly with horizontal line from foramen rotundum) and reaching temporal lobe anterior pole with opening dura mater. Conclusions Temporal lobe anterior pole is accessible safely via transmaxillary transpterygoideal approach by using endoscope while preserving neurovasculer structures. This approach provides safe access to the anterior temporal lobe without craniotomy and parenchyma retraction, as an alternative to transcranial approaches. We predict that surgery of anterior temporal lobe lesions, can be performed with this approach. endoscopic sublabial approach middle cranial fossa skull base transmaxillary approach Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The approaches for Middle cranial fossa region can be categorized as transcranial and endoscopic approaches. Endoscopic approaches can be further categorized as endonasal and sublabial approaches. These approaches can be combined and utilized with various modifications and each approach has limitation due to maneuverability of the endoscope. The use of endoscopes in skull base surgery has been expanding day by day with the advancements in surgical instruments and reconstructive techniques.[ 11 ] The development of modern endoscopic skull base surgery is result of technical progress and the application of fundamental principles of neurosurgery.[ 20 ] These advancements make endoscopic approaches a viable alternative to transcranial approaches.[ 7 ] The endoscopic sublabial transmaxillary approach has been used to reach middle cranial fossa lesions, but the complexity of anatomy requires a detailed anatomical knowledge to perform this approach. This study aims defining the key anatomical landmarks of this corridor, defining the boundaries of the craniectomy in an appliable and clear way, and a detailed anatomical framework of the sublabial endoscopic transmaxillary transpterygoidal approach to the middle cranial fossa (ETTAMCF). Results Endoscopic dissections were categorized into three stages; premaxillary sinusoidal, maxillary sinusoidal, and post maxillary sinusoidal stages respectively. 1. Premaxillary Sinusoidal Stage The head was positioned in a neutral supine position and secured to the Mayfield head clamp parallel to the horizontal plane as a simulation of the surgery. Upper lip was retracted macroscopically using suspensory sutures (Fig. 1 A). Then, incision line in dentogingival sulcus was aligned to correspond with the projection of the vestibulum oris between the left canine tooth and second molar tooth (Fig. 1 B). Due to fragility of mucosal tissue in cadaveric specimens, special care has been taken during retractor placement. The musoca was incised along the line using No. 10 scalpel. The mucosal layer and the periosteal layer were dissected until the infraorbital foramen, then the infraorbital nerve were seen by using the periosteal rugine (Fig. 1 C). The dissection was extended to get enough exposure of the anterior maxillary wall, then a self retaining retractor was placed (Fig. 1 C). Since the mucosal layer was very fragile, dissection and placing the retractor was carefully done. Sublabial anterior antrostomy made with Caldwell-Luc procedure. A maxillotomy approximately 2x3 cm in size was performed in the anterior maxillary wall by using the high-speed drill (Fig. 1 D). The infraorbital foramen made the superior border of the craniotomy to protect the neurovascular structures. After entering the maxillary sinus, the lateral and medial borders were extended to the transition points of the anterior maxillary sinus wall into the lateral and medial walls of the maxillary sinus. The base of the maxillary sinus was preserved as the inferior border to avoid damaging the anterior superior alveolar nerve (ASAN), middle superior alveolar nerve (MSON, and branches of the infraorbital nerve (ION) which receives sensory input from upper teeth. 2. Maxillary Sinusoidal Stage With the entrance to the maxillary sinüs, the endoscopic stage was initiated (Fig. 2 A). As a first step of the maxillary sinusoidal stage, the mucosal lining was removed to reveal the anatomical landmarks (Fig. 2 B). Medially, maxillary ostium which opens into the midlle meatus, as well as the infraorbital nerve and infraorbital artery extending from the posterior wall to the superior wall were identified. Laterally apex of the maxillary sinus was observed. The most critical part of this stage is preserving the inferior orbital wall while drilling the posterior maxillary wall. Superior boundary during the drilling process of the posterior maxillary wall is the finishing line of the orbital prominence. The anatomical landmarks of this stage are the infraorbital nerve (ION) and the infraorbital artery (IOA). Posterior maxillary wall, medial to the ION and inferior to the orbital prominence, was drilled. Then, a window was opened through the posterior maxillary wall while preserving the neurovascular and muscular structures. At this stage, it is possible to widen this opening by using the Kerrison roungeur to get appropriate exposure. 3. Postmaxillary Sinusoidal Stage Through the opening of the posterior maxillary wall, infratemporal fossa and pterygoid fossa were identified. Main anatomical landmark of this stage is the ION. Via following the ION, maxillary sinus and foramen rotundum were seen and this region was very rich in neurovascular and muscular structures (Fig. 3 A). Laterally, temporal and medial pterygoid muscle, medially, sphenopalatine artery, posteriorly, superior head of lateral pterygoid muscle which inserted to the infratemporal crest, inferiorly, superior head of lateral pterygoid muscle were seen. At this stage, lateral ptergygoid lamina can be drilled more, however the drilling of the medial pterygoid lamina is not within safe limits. (Fig. 3 B). Vidian canal and the vidian nerve were located posteriorly to the sphenopalatine artery and foramen. In this region, sphenopalatine artery lying medial to the pterygomaxillary fissure, goes into the nasal cavity and suppliess the nasal septum. Opening a window to the middle fossa necessitates sacrification of the superior head of the lateral pterygoid muscle originating from the infratemporal crest and inserting on the temporomandibular joint capsule and disc. Inferior head of the lateral pterygoid muscle, which originates from the lateral pterygoid lamina of the sphenoid bone and make insertion to the mandibular pterygoid fovea, was incised starting from the infratemporal crest to visualize the greater wing of the sphenoid bone. The bony window reaching the middle cranial fossa is through the greater wing of the sphenoid bone. External carotid artery gives rise to the superficial temporal artery and the maxillary artery branches just posterior to the mandible. The maxillary artery enters the infratemporal fossa supplying the structures within the infratemporal fossa, the pterygoid fossa, dura mater, teeth, pharynx and nasal septum. The most important step of this stage is to determine the boundaries of the rectangle opening to the middle cranial fossa, and definition of the foramen ovale and the foramen rotundum is crucial (Fig. 4 A). At this stage, the endoscope’s ability to provide a panoramic view offers an advantage in identifying these two foramina by enhancing spatial awareness and control. To define the foramen rotundum, proximal ION should be followed where maxillary nerve (V2) is visualized. Once defining the V2, endoscope is directed inferolaterally to reach the exit of the mandibular nerve (V3) which is the FO (Fig. 4 ). It is crucial to keep in mind during drilling that V2-V3 junction is located between the FO and FR. Firstly, the vertical imaginary line passing through the foramen rotundum and the horizontal imaginary line passing through the foramen ovale were drawn. The safest quadrant is the superolateral quadrant, since this region meets the greater wing of the sphenoid bone (Fig. 4 ). After drilling the superolateral quadrant of the greater wing of the sphenoid bone, the dura of the anterior temporal pole was visualized (Fig. 5 A). To get greater visualization angle, pivot of the endoscope was moved distally. From this point on, dural incision can be planned according the lesion. After dural incision, anterior temporal pole parenchyma was visualized, and medial to the anterior temporal pole, Meckel’s cave, petrous apex and the cavernous sinus can be exposed (Fig. 5 B). Methods & Materials This study was conducted at the laboratory between September and October 2021. Twelve formalin fixed cadaveric hemispheres in which the arteris were perfused with red and the veins with blue silicone were used for his study. Phases of macroscopic and microscopic dissections were photographed using the Canon EOS 550D with 18–55 mm and 100 mm macro lenses while endoscopic phases were captured vith 4K Storz and Richard-Wolf Logic 4K Endoscope system. Microscopic dissections were performed under the Carl Zeiss (AG, Oberkochen, Germany) and combined with the endoscope (4K Storz and Richard-Wolf Logic 4K Endoscope system). Between the dissections cadaveric specimens were preserved in %70 alcohol solution at room temperature. Specimens were supine positioned as in the surgical position. Dissections were performed in three stages; premaxillary sinusoidal, maxillary sinusoidal, and postmaxillary sinusoidal stages respectively. Results Endoscopic dissections were categorized into three stages; premaxillary sinusoidal, maxillary sinusoidal, and post maxillary sinusoidal stages respectively. 1. Premaxillary Sinusoidal Stage The head was positioned in a neutral supine position and secured to the Mayfield head clamp parallel to the horizontal plane as a simulation of the surgery. Upper lip was retracted macroscopically using suspensory sutures (Figure 1A). Then, incision line in dentogingival sulcus was aligned to correspond with the projection of the vestibulum oris between the left canine tooth and second molar tooth (Figure 1B). Due to fragility of mucosal tissue in cadaveric specimens, special care has been taken during retractor placement. The musoca was incised along the line using No. 10 scalpel. The mucosal layer and the periosteal layer were dissected until the infraorbital foramen, then the infraorbital nerve were seen by using the periosteal rugine (Figure 1C). The dissection was extended to get enough exposure of the anterior maxillary wall, then a self retaining retractor was placed (Figure 1C). Since the mucosal layer was very fragile, dissection and placing the retractor was carefully done. Sublabial anterior antrostomy made with Caldwell-Luc procedure. A maxillotomy approximately 2x3 cm in size was performed in the anterior maxillary wall by using the high-speed drill (Figure 1D). The infraorbital foramen made the superior border of the craniotomy to protect the neurovascular structures. After entering the maxillary sinus, the lateral and medial borders were extended to the transition points of the anterior maxillary sinus wall into the lateral and medial walls of the maxillary sinus. The base of the maxillary sinus was preserved as the inferior border to avoid damaging the anterior superior alveolar nerve (ASAN), middle superior alveolar nerve (MSON, and branches of the infraorbital nerve (ION) which receives sensory input from upper teeth. 2. Maxillary Sinusoidal Stage With the entrance to the maxillary sinüs, the endoscopic stage was initiated (Figure 2A). As a first step of the maxillary sinusoidal stage, the mucosal lining was removed to reveal the anatomical landmarks (Figure 2B). Medially, maxillary ostium which opens into the midlle meatus, as well as the infraorbital nerve and infraorbital artery extending from the posterior wall to the superior wall were identified. Laterally apex of the maxillary sinus was observed. The most critical part of this stage is preserving the inferior orbital wall while drilling the posterior maxillary wall. Superior boundary during the drilling process of the posterior maxillary wall is the finishing line of the orbital prominence. The anatomical landmarks of this stage are the infraorbital nerve (ION) and the infraorbital artery (IOA). Posterior maxillary wall, medial to the ION and inferior to the orbital prominence, was drilled. Then, a window was opened through the posterior maxillary wall while preserving the neurovascular and muscular structures. At this stage, it is possible to widen this opening by using the Kerrison roungeur to get appropriate exposure. 3. Postmaxillary Sinusoidal Stage Through the opening of the posterior maxillary wall, infratemporal fossa and pterygoid fossa were identified. Main anatomical landmark of this stage is the ION. Via following the ION, maxillary sinus and foramen rotundum were seen and this region was very rich in neurovascular and muscular structures (Figure 3A). Laterally, temporal and medial pterygoid muscle, medially, sphenopalatine artery, posteriorly, superior head of lateral pterygoid muscle which inserted to the infratemporal crest, inferiorly, superior head of lateral pterygoid muscle were seen. At this stage, lateral ptergygoid lamina can be drilled more, however the drilling of the medial pterygoid lamina is not within safe limits. (Figure 3B). Vidian canal and the vidian nerve were located posteriorly to the sphenopalatine artery and foramen. In this region, sphenopalatine artery lying medial to the pterygomaxillary fissure, goes into the nasal cavity and suppliess the nasal septum. Opening a window to the middle fossa necessitates sacrification of the superior head of the lateral pterygoid muscle originating from the infratemporal crest and inserting on the temporomandibular joint capsule and disc. Inferior head of the lateral pterygoid muscle, which originates from the lateral pterygoid lamina of the sphenoid bone and make insertion to the mandibular pterygoid fovea, was incised starting from the infratemporal crest to visualize the greater wing of the sphenoid bone. The bony window reaching the middle cranial fossa is through the greater wing of the sphenoid bone. External carotid artery gives rise to the superficial temporal artery and the maxillary artery branches just posterior to the mandible. The maxillary artery enters the infratemporal fossa supplying the structures within the infratemporal fossa, the pterygoid fossa, dura mater, teeth, pharynx and nasal septum. The most important step of this stage is to determine the boundaries of the rectangle opening to the middle cranial fossa, and definition of the foramen ovale and the foramen rotundum is crucial (Figure 4A). At this stage, the endoscope’s ability to provide a panoramic view offers an advantage in identifying these two foramina by enhancing spatial awareness and control. To define the foramen rotundum, proximal ION should be followed where maxillary nerve (V2) is visualized. Once defining the V2, endoscope is directed inferolaterally to reach the exit of the mandibular nerve (V3) which is the FO (Figure 4). It is crucial to keep in mind during drilling that V2-V3 junction is located between the FO and FR. Firstly, the vertical imaginary line passing through the foramen rotundum and the horizontal imaginary line passing through the foramen ovale were drawn. The safest quadrant is the superolateral quadrant, since this region meets the greater wing of the sphenoid bone (Figure 4). After drilling the superolateral quadrant of the greater wing of the sphenoid bone, the dura of the anterior temporal pole was visualized (Figure 5A). To get greater visualization angle, pivot of the endoscope was moved distally. From this point on, dural incision can be planned according the lesion. After dural incision, anterior temporal pole parenchyma was visualized, and medial to the anterior temporal pole, Meckel’s cave, petrous apex and the cavernous sinus can be exposed (Figure 5B). Discussion Middle cranial fossa lesions can be accessed through the transcranial approaches that have been used in neurosurgical practice for years. Moreover, with increasing use of endoscopy in skull base surgery, novel techniques have been defined. Rostral middle cranial fossa lesions can be reached by transcranial routes, such as subtemporal, pterional and orbitozygomatic approaches. However, especially with the subtemporal approach, reaching the rostral middle cranial fossa requires retraction of the anterior temporal lobe. Additionally, temporal muscle is incised and elevated to perform temporal craniotomy which may lead atrophy of the temporal muscle causing decline in the patient’s quality of life.[ 12 , 13 , 24 ] In addition to these, the paramedian supracerebellar-transtentorial approach, described by Türe et al. is also among the alternative methods to reach the anterior temporal pole. The approach we have defined and this approach align linearly in the same plane, complementing each other.[ 19 ] In addition to transcranial approaches many approaches have been defined to reach the sphenoidal rostrum and even the Meckel’s cave.[ 2 , 16 , 18 , 21 ] It is possible to reach the Meckel’s cave both endoscopically and microscopically. Among them, anterior (sublabial transmaxillary transpterygoid) and anteromedial (endoscopic endonasal transpterygoid transsphenoidal) approaches can be counted.[ 3 , 6 , 15 , 20 , 25 , 26 ] Furthermore, endoscopic endonasal, transoral sublabial, and transorbital methods have been used to access the infratemporal fossa.[ 27 ] The endoscopic endonasal transmaxillary transpterygoid approach has been used to reach middle cranial fossa lesions and offers a minimally invasive route to pterygopalatine fossa, infratemporal fossa, sphenoid sinus, cavernous sinus, petrous apex, and the Meckel’s cave.[ 8 ] With this approach sphenopalatine artery is cauterized and transected, the palatine bone is drilled, then the lateral recess of the sphenoid sinus and pterygopalatine fossa was exposed.[ 28 ] It is possible to reach the anterior fossa to the odontoid process in sagittal plane, and both foramen ovale in coronal plane via pure endoscopic endonasal approaches.[ 14 ] Transoral sublabial approach to maxillary sinuses was first described by George Caldwell of the U.S.A and Henri Luc of France in 19th century, during the pre-endoscopic era, to treat medically resistant maxillary sinusitis.[ 29 ] With time, it has been used to access pathologies in maxillary sinus, orbital floor, pterygopalatine fossa and infratemporal fossa pathologies.[ 29 , 30 ] Couldwell et al. extended sublabial transmaxillary approach to the anterior cavernous sinus by enlarging the superomedial border of the foramen rotundum.[ 3 ] Later, Gady Har-el defined a combined endoscopic transmaxillary and transnasal approach to the pterygoid region, lateral sphenoid sinus, and retrobulbar orbit.[ 31 ] Previous studies have demonstrated that the sublabial transmaxillary transpterygoid approach to Meckel’s cave and the middle cranial fossa allows better exposure in the sagittal plane compared to the endoscopic endonasal approaches.[ 5 , 22 ] Furthermore, while accessing the foramen ovale and rotundum, sublabial endoscopic approaches offers superiority over endoscopic endonasal approaches in terms of surgical field of view and surgical comfort. [ 5 , 22 ] Endonasal and sublabial endoscopic transmaxillary approaches can be combined to access the pterygopalatine fossa and orbital apex. Endonasal approach provides limited lateral exposure to the pterygopalatine fossa and infratemporal fossa, because it is limited by the nasal septum, nasolacrimal duct and pterygoid plates.[ 1 , 32 ] Better exposure with endonasal route requires ethmoidectomy and sphenoidotomy or an inferior turbinectomy which may lead to different complications.[ 1 ] Therefore, better exposure can be obtained with combining endonasal approach with the sublabial approach which is not limited by the nasal septum and nasolacrimal duct.[ 1 , 30 , 32 ] Kassam et al., described an expanded endonasal approach for the middle cranial fossa and infratemporal fossa.[ 25 ] This approach requires endoscopic middle turbinectomy with the use of 45–70 degree endoscope which increases technical difficulty and the risk of complications.[ 1 , 25 ] Truong and Sun et al. described the sublabial transmaxillary transalisphenoidal approach to the middle cranial fossa and Meckel’s cave in their anatomic study with two cases. In this approach, after sublabial incision, the foramen rotundum, foramen ovale and the infraorbital nerve are defined endoscopically, then the greater wing of the sphenoid is drilled to expose the anterior dural wall of middle fossa and Meckel’s cave.[ 18 ] It has been stated that the least invasive approach to treat trigeminal nerve pathologies such as squamous cell carcinoma, basal cell carcinoma, melanomas and adenoid cystic carcinomas is the endoscopic transmaxillary approach.[ 2 , 16 , 18 , 21 ] DeMonte et al., described the microneurosurgical way of approach to the malignant maxillary nerve tumor with perineuroal extension, and they suggest the use of endoscope due to its advantages. [ 4 ] In the literature, the sublabial transatral approaches have been reported to have certain advantages over the endonasal endoscopic approaches; 1) the use of endoscopes with angles greater than 30 degrees is not required 2) nerves within the pterygopalatine fossa, including the maxillary nerve, vidian nerve, and pterygopalatine ganglion, are not manipulated 3) it allows for easier exposure of the compartments lateral to the pterygopalatine fossa (sphenoidal rostrum, infratemporal fossa). [ 13 , 31 ] Ong et al. listed the potential complications of the endoscopic sublabial transmaxillary transpterygoid approach to middle cranial fossa as; complications related to the sublabial incision and maxillotomies, damage to the retromaxillary neurovascular structures, some chewing problems due to manipulation of the lateral pterygoid muscles, and cerebrospinal fluid fistula.[ 13 ] As a result, facial anesthesia/dysesthesia, dental anesthesia, oroantral fistula can be seen.[ 23 ] Moreover, proper repair may be necessary not to have cerebrospinal fluid fistula.[ 23 ] Furthermore, fat graft fixation techiques can be applied as explained by Luzzi et al.[ 10 ] Yağmurlu et al., described the sublabial transmaxillary approach to Meckel’s cave in their cadaveric study.[ 23 ] It was stated that this approach provides extradural access to lateral portion of the Meckel’s cave with great visualization for selected cases.[ 23 ] The maxillary artery is sacrificed to make lateral pterygoid muscle free in this approach.[ 23 ] The boundaries of the craniectomy defined as; starts at foramen rotundum, proceeds in a 6 to 12 o’clock direction to the foramen ovale laterally.[ 23 ] Superior boundary is the upper head of the lateral pterygoid muscle and the inferior boundary is the imaginary line drawn between the lowermost edges of the foramen ovale and the foramen rotundum.[ 23 ] Foramen ovale is drilled superolateraly to protect the eustachian tube.[ 23 ] Theodosopoulos et al. reach the infratemporal fossa combining Caldwell-Luc and endonasal transmaxillary approaches.[ 17 ] Thus, they expanded the boundaries of both approaches, providing exposure to even middle meningeal artery and the upper cervical carotid artery.[ 17 ] While endonasal approaches are more appropriate for lesions in the medial nasal cavity and medial orbit, the sublabial approaches offer better exposure for lateral middle cranial fossa lesions. In some instances, two approaches can be combined. In our cadaveric study, we demonstrated that the transmaxillary middle fossa approach with sublabial incision resulted in minimal brain parenchyma retraction. Furthermore, since our approach is performed mainly via the sublabial incision, with no incison on the temporal muscle, the risk of temporal muscle atrophy and related cosmetic issues won’t be consideration. During the dissections, after the maxillotomy, lateral to the branches of the maxillary artery and the branches of the maxillary nerve was exposed like previous studies. During dissections, angled endoscopes were not used since straight endoscopes provides excellent exposure. With this approach beside having the excellent view of the lateral infratemporal fossa, possible maxillary artery injuries can be controlled over. In addition to those, the safe zone was identified according to the main anatomical landmarks. Since the anatomy of the middle cranial fossa and the endoscopic routes reaching there comprise a complex anatomy, we aimed to define the craniectomy borders in a more simple way by using two prominent structures; foramen ovale and foramen rotundum. In this way, we aimed a safe surgical corridor which allowing enough exposure. The volume of maxillary sinus forms a natural corridor leading to the retromaxillary space allowing for free movement of surgical instruments. [ 9 ] Furthermore, in the endonasal approach, the sphenopalatine artery, which needs to be transected for the middle fossa approach, has been freely exposed and preserved in this approach. In the middle cranial fossa approaches, the most suitable approach is determined based on the location of the lesion and the desired angle of attack. A deep understanding of the gross and endoscopic anatomy of the pterygopalatine and infratemporal fossa is crucial for this approach like other approaches to the skull base. With detailed description of the anatomical landmarks and the boundaries of the maxillotomy in this study, the middle cranial fossa can be accessed safely using the sublabial transmaxillary approach, which provides the necessary exposure. Abbreviations ETTAMCF endoscopic transmaxillary transpterygoidal approach to the middle cranial fossa ASAN anterior superior alveolar nerve MSON middle superior alveolar nerve ION infraorbital nerve IOA the infraorbital artery V2 maxillary nerve V3 mandibular nerve Declarations Compliance with Ethical Standards Ethics approval: This study was performed inaccordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. . This study was conducted with the approval of the Başakşehir Çam and Sakura City Hospital Clinical Research Ethics Committee, dated September 8, 2021, with protocol number 2021-201, confirming its ethical and regulatory compliance. Conflict of interest: The authors declare that they have no conflict of interest. The manuscript does not contain clinical studies or patient data. Funding’ and/or ‘Competing interests Competing interests and Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Employment: The authors have no recent, current, or anticipated employment with any organization that may gain or lose financially through the publication of this manuscript. Financial Interests: The authors declare they have no financial interests. No funding was received to assist with the preparation of this manuscript. No funding was received for conducting this study. No funds, grants, or other support was received. Non-Financial Interests : The authors declare no non-financial interests that could influence the interpretation or presentation of the data, such as advisory roles, editorial positions, mentoring relations, or personal beliefs. Additional information: This study was conducted at Prof. Rhoton Applied Anatomy and Surgical Training Center, Bahçeşehir University School of Medicine. We certify that the content of this manuscript, in part or in full, has not been submitted to any other journal in any form, and its publication has been approved by all co-authors. The authors have no relevant financial or non-financial interests to disclose. Authors’ contributions: All authors contributed to the study conception and design. Conceptualization: Ebubekir Akpınar,Hasan Çağrı Postuk ; Methodology: Aysu İyigün Kabakcı, Ebubekir Akpınar ; Formal analysis and investigation: Ercan Boşnak, Hasan Çağrı Postuk ; Writing - original draft preparation: Aysu İyigün Kabakcı, Ebubekir Akpınar ; Writing - review and editing: Abuzer Güngör, Akın Akakın , Ercan Boşnak ; Supervision: Abuzer Güngör, Bekir Tuğcu, Türker Kılıç, All authors read and approved the final manuscript References Alimohamadi M, Hajiabadi M, Gerganov V, Fahlbusch R, Samii M (2015) Combined endonasal and sublabial endoscopic transmaxillary approach to the pterygopalatine fossa and orbital apex. Acta Neurochir (Wien) 157(6):919–929 Amit M, Eran A, Billan S, Fridman E, Na’ara S, Charas T, Gil Z (2016) Perineural Spread in Noncutaneous Head and Neck Cancer: New Insights into an Old Problem. 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European Archives of Oto-Rhino-Laryngology 271(4):787–794 Singh FM, Mak SY, Bonington SC (2015) Patterns of spread of head and neck adenoid cystic carcinoma. Clin Radiol 70(6):644–653 Theodosopoulos P V., Guthikonda B, Brescia A, Keller JT, Zimmer LA (2010) Endoscopic approach to the infratemporal fossa: Anatomic study. Neurosurgery 66(1):196–202 Truong HQ, Sun X, Celtikci E, Borghei-Razavi H, Wang EW, Snyderman CH, Gardner PA, Fernandez-Miranda JC (2019) Endoscopic anterior transmaxillary “transalisphenoid” approach to Meckel’s cave and the middle cranial fossa: An anatomical study and clinical application. J Neurosurg 130(1):227–237 Türe U, Harput MV, Kaya AH, Baimedi P, Firat Z, Türe H, Bingöl CA (2012) The paramedian supracerebellar-transtentorial approach to the entire length of the mediobasal temporal region: An anatomical and clinical study - Laboratory investigation. J Neurosurg 116(4):773–791 Wang X, Zhang X, Hu F, Yu Y, Gu Y, Xie T, Ge J (2016) Image-guided endoscopic endonasal transmaxillary transpterygoid approach to Meckel’s cave. Turk Neurosurg 26(2):309–314 Warren TA, Nagle CM, Bowman J, Panizza BJ (2016) The Natural History and Treatment Outcomes of Perineural Spread of Malignancy within the Head and Neck. J Neurol Surg B Skull Base 77(2):107–112 Wilson DA, Williamson RW, Preul MC, Little AS (2014) Comparative analysis of surgical freedom and angle of attack of two minimal-access endoscopic transmaxillary approaches to the anterolateral skull base. World Neurosurg 82(3):E487–E493 Yağmurlu K, Mooney MA, Almefty KK, Bozkurt B, Tanrıöver N, Little AS, Preul MC (2018) An Alternative Endoscopic Anterolateral Route to Meckel’s Cave: An Anatomic Feasibility Study Using a Sublabial Transmaxillary Approach. World Neurosurg 114:134–141 Andrade, F. C. d., FILHO, C. M. D. A., & FILHO, J. C. (1998). Dysfunction of the temporalis muscle after pterional craniotomy for intracranial aneurysms: comparative, prospective and randomized study of one flap versus two flaps dieresis. Arquivos De Neuro-Psiquiatria, 56(2), 200-205. https://doi.org/10.1590/s0004-282x1998000200006. Kassam, A. B., Gardner, P., Snyderman, C., Mintz, A., & Carrau, R. (2005). Expanded endonasal approach: fully endoscopic, completely transnasal approach to the middle third of the clivus, petrous bone, middle cranial fossa, and infratemporal fossa. Neurosurgical focus, 19(1), E6. Cavallo, L. M., Messina, A., Gardner, P., Esposito, F., Kassam, A. B., Cappabianca, P., de Divitiis, E., & Tschabitscher, M. (2005). Extended endoscopic endonasal approach to the pterygopalatine fossa: anatomical study and clinical considerations. Neurosurgical focus, 19(1), E5. Tabari, A., Nasirmohtaram, S., Mohammadi, H. R., Zeinalizadeh, M., & Sadrehosseini, S. M. (2024). Anterior endoscopic sublabial transmaxillary access to middle cranial base lesions. Head & neck, 46(5), 1028–1042. https://doi.org/10.1002/hed.27725 Schwartz, T. H., Fraser, J. F., Brown, S., Tabaee, A., Kacker, A., & Anand, V. K. (2008). Endoscopic cranial base surgery: classification of operative approaches. Neurosurgery, 62(5), 991–1005. https://doi.org/10.1227/01.neu.0000325861.06832.06 Macbeth R. (1971). Caldwell, Luc, and their operation. The Laryngoscope, 81(10), 1652–1657. https://doi.org/10.1288/00005537-197110000-00011 Matheny, K. E., & Duncavage, J. A. (2003). Contemporary indications for the Caldwell-Luc procedure. Current opinion in otolaryngology & head and neck surgery, 11(1), 23–26. https://doi.org/10.1097/00020840-200302000-00005 Har-El G. (2005). Combined endoscopic transmaxillary-transnasal approach to the pterygoid region, lateral sphenoid sinus, and retrobulbar orbit. The Annals of otology, rhinology, and laryngology, 114(6), 439–442. https://doi.org/10.1177/000348940511400605 Har-El G. (2005). Combined endoscopic transmaxillary-transnasal approach to the pterygoid region, lateral sphenoid sinus, and retrobulbar orbit. The Annals of otology, rhinology, and laryngology, 114(6), 439–442. https://doi.org/10.1177/000348940511400605 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6795600","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":465726480,"identity":"8a9a9fc8-c6f6-4cf3-956d-b07e42913bd7","order_by":0,"name":"Ebubekir Akpınar","email":"","orcid":"","institution":"Republic of Türkiye Ministry of Health Başakşehir Çam ve Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ebubekir","middleName":"","lastName":"Akpınar","suffix":""},{"id":465726483,"identity":"03d48ad0-3906-43f0-8c84-3702ceb299b3","order_by":1,"name":"Aysu İyigün Kabakcı","email":"","orcid":"","institution":"Republic of Türkiye Ministry of Health Ankara Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aysu","middleName":"İyigün","lastName":"Kabakcı","suffix":""},{"id":465726484,"identity":"a12f3faf-ac8a-4475-ac56-13b2ca012c6c","order_by":2,"name":"Hasan Çağrı Postuk","email":"","orcid":"","institution":"Trabzon Kanuni Research and Education Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hasan","middleName":"Çağrı","lastName":"Postuk","suffix":""},{"id":465726487,"identity":"6a252e4d-cadb-4a27-9de3-39cf58f9fafa","order_by":3,"name":"Ercan Boşnak","email":"","orcid":"","institution":"Medicalpark Gebze Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ercan","middleName":"","lastName":"Boşnak","suffix":""},{"id":465726488,"identity":"6a85ee82-9517-42aa-868d-49ced9177d0e","order_by":4,"name":"Akın Akakın","email":"","orcid":"","institution":"Bahcesehir University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Akın","middleName":"","lastName":"Akakın","suffix":""},{"id":465726490,"identity":"69f04a83-0ea2-4874-82eb-8f03a68d0212","order_by":5,"name":"Abuzer Güngör","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYDACCWTOByBmYydFC+MMkBZmUrQw84BJAjr4Z/cYf/i4pzZxO//iY59tfm2T52NmYPzwMQePJXfOGBjOeHY8ceeMZ8mzc/tuG7YxMzBLztyGx5obOQbJPAeOJW64ccaYObfnNiNQCxszLx4t8kAth//AtFj23LYnqMXgRo5hM8OBmsQN53uMmRl+3E4kqMXwzrFixp4DB4w33GBLZuxtuJ3cxszYjNcvcrebN3/4caBOdsP5w4cZfvy5bTu/vfngh4/4vA8Bh4FhlwCMyzYQh7GBoHogqAPG0AEg/YcYxaNgFIyCUTDSAAAg31itLTPuswAAAABJRU5ErkJggg==","orcid":"","institution":"İstinye University Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Abuzer","middleName":"","lastName":"Güngör","suffix":""},{"id":465726491,"identity":"9359125f-d4d7-4e1a-8404-7ed1ba4a6d90","order_by":6,"name":"Türker Kılıç","email":"","orcid":"","institution":"İstinye University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Türker","middleName":"","lastName":"Kılıç","suffix":""},{"id":465726492,"identity":"0eb0d764-efcd-4d3d-a360-79009c4ce4f2","order_by":7,"name":"Bekir Tuğcu","email":"","orcid":"","institution":"Republic of Türkiye Ministry of Health Başakşehir Çam ve Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bekir","middleName":"","lastName":"Tuğcu","suffix":""}],"badges":[],"createdAt":"2025-06-01 12:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6795600/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6795600/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84202648,"identity":"5dfe7e09-df32-44cb-8d1f-b2bdf5521741","added_by":"auto","created_at":"2025-06-09 08:39:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":66982,"visible":true,"origin":"","legend":"\u003cp\u003ePremaxillary Sinusoidal Stage a. Opening the vestibular oris located between the teeth and the upper lip after aplying ecartation on the lips b. Mucosal incision was planned as outlined in the dentogingival sulcus c. After dissection of the mucosal layer and elevating the periosteal layer, the infraorbital foramen, the infraorbital nerve, and anterior maxillary wall were reached d. Drilling of the anterior maxillary sinus wall is shown. Due to thin structure in anterior maxillary wall, drilling must be started at the safe point. An imaginary vertical line drawn from the IOF to the dentogingival sulcus should be considered, and the first drill point should be targeted at the exact midpoint of this line.\u003c/p\u003e\n\u003cp\u003e*: superior labial phrenulum ion: infraorbital nerve\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6795600/v1/13903be9c8744fcd7ee31c22.jpg"},{"id":84202641,"identity":"b19a52bf-e4a0-4bd6-865d-5be0c58a573b","added_by":"auto","created_at":"2025-06-09 08:39:05","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":39127,"visible":true,"origin":"","legend":"\u003cp\u003eMaxillary sinusoidal stage a. Endoscopic view of left maxillary sinus with musocal lining b. Endoscopic view after elevation of the mucosa allows surgeon to reveal the anatomic landmarks such as maxillary ostium, apex, posterior maxillar wall, infraorbital foramen and nerve, and orbital floor.\u003c/p\u003e\n\u003cp\u003e*: maxillary ostium iof: infraorbital foramen ion: infraorbital nerve m: medial l: lateral\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6795600/v1/05c41f6f5ed54020528dceb5.jpg"},{"id":84202690,"identity":"1276aa72-97bf-43aa-b269-5925e6bf9a25","added_by":"auto","created_at":"2025-06-09 08:39:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":38464,"visible":true,"origin":"","legend":"\u003cp\u003ePostmaxillary sinusoidal stage-1; a. Endoscopic view after drilling the posterior maxillary wall. The two prominent anatomical structures are the maxillary artery and maxillary branch of the trigeminal nerve. V2 exits cranium passing through the foramen rotundum, gives anterior, middle and posterior superior alveolar nerve branches then reaches the infraorbital foramen. Two branches of the maxillary artery, sphenopalatine artery and infraorbital artery, are visualized. b. Endoscopic view showing the infratemporal structures after drilling the lateral pterygoid lamina and the bony region medial to the infraorbital nerve in addition to posterior maxillary wall allowing visualization of the pterygopalatine fossa.\u003c/p\u003e\n\u003cp\u003easan: anterior superior alveolar nerve l: lateral m: medial ma: maxillary artery msan: middle superior alveolar nerve inf. head: inferior head of the lateral pterygoid muscle ioa: infraorbital artery ion: infraorbital nerve psan: posterior superior alveolar nerve spa: sphenopalatine artery sup. head: superior head of the lateral pterygoid muscle.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6795600/v1/026d3095fc4cc68e468bf4d8.jpg"},{"id":84202640,"identity":"1de65572-328c-4e23-908d-cc7d20b6a8d1","added_by":"auto","created_at":"2025-06-09 08:39:05","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":81351,"visible":true,"origin":"","legend":"\u003cp\u003eEndoscopic view of the greater wing of the sphenoid bone. The superior head of the lateral pterygoid muscle is incised starting at the infratemporal crest. The inferior head of the lateral pterygoid and the medial pterygoid muscle are retracted. Thus, the greater wing of the sphenoid bone and related structures are visualized. Maxillary branch of the trigeminal nerve serves as a guide to locate the foramen rotundum while mandibular branch locating the foramen ovale. Foramen rotundum is delineated by black dots and foramen ovale is delineated by white dots. To define the boundaries of the rectangle opening into the middle cranial fossa quadrant technique is used not to damage any structures. Firstly, the vertical imaginary yellow line passing through the foramen rotundum and the horizontal imaginary yellow line passing through the foramen ovale were drawn. The safest quadrant is the superolateral quadrant since this region meets the greater wing of the sphenoid bone. Medially, the sphenopalatine artery going to the nasal septum and the descending palatine going to the hard and soft palate.\u003c/p\u003e\n\u003cp\u003edpa: descending palatine artery FO: foramen ovale FR: forament rotundum ioa: infraorbital artery ion: infraorbital nerve M: medial L: lateral spa: sphenopalatine artery V2: maxillary branch of the trigmeinal nerve V3: mandibular branch of the trigeminal nerve\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6795600/v1/4a243c13cb25386cce84ec5c.jpg"},{"id":84202599,"identity":"4ec9e013-e74f-4b80-826f-0fedde2c3414","added_by":"auto","created_at":"2025-06-09 08:39:01","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":41573,"visible":true,"origin":"","legend":"\u003cp\u003eEndoscopic view of the middle temporal fossa after drilling the greater wing of the sphenoid bone. a. An opening through the greater wing of the sphenoid bone firstly the dura mater of the anterior temporal bone is encountered. During the operation this opening can be expanded laterally b. After dural opening parenchyma of the anterior temporal pole is seen.\u003c/p\u003e\n\u003cp\u003em: medial l: lateral\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6795600/v1/d39dfcfde6c9456e3743db34.jpg"},{"id":84316035,"identity":"027f06d6-6e1b-47cf-8958-2be34e9c22ed","added_by":"auto","created_at":"2025-06-10 13:24:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":966268,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6795600/v1/d593aca5-5864-4047-b5f8-417a4c1bcdd4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eDefining the Safe Zone; the Endoscopic Sublabial Transmaxillary Approach to the Middle Cranial Fossa\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe approaches for Middle cranial fossa region can be categorized as transcranial and endoscopic approaches. Endoscopic approaches can be further categorized as endonasal and sublabial approaches. These approaches can be combined and utilized with various modifications and each approach has limitation due to maneuverability of the endoscope. The use of endoscopes in skull base surgery has been expanding day by day with the advancements in surgical instruments and reconstructive techniques.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The development of modern endoscopic skull base surgery is result of technical progress and the application of fundamental principles of neurosurgery.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] These advancements make endoscopic approaches a viable alternative to transcranial approaches.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe endoscopic sublabial transmaxillary approach has been used to reach middle cranial fossa lesions, but the complexity of anatomy requires a detailed anatomical knowledge to perform this approach. This study aims defining the key anatomical landmarks of this corridor, defining the boundaries of the craniectomy in an appliable and clear way, and a detailed anatomical framework of the sublabial endoscopic transmaxillary transpterygoidal approach to the middle cranial fossa (ETTAMCF).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eEndoscopic dissections were categorized into three stages; premaxillary sinusoidal, maxillary sinusoidal, and post maxillary sinusoidal stages respectively.\u003c/p\u003e \u003cp\u003e \u003cb\u003e1. Premaxillary Sinusoidal Stage\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe head was positioned in a neutral supine position and secured to the Mayfield head clamp parallel to the horizontal plane as a simulation of the surgery. Upper lip was retracted macroscopically using suspensory sutures (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Then, incision line in dentogingival sulcus was aligned to correspond with the projection of the vestibulum oris between the left canine tooth and second molar tooth (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Due to fragility of mucosal tissue in cadaveric specimens, special care has been taken during retractor placement. The musoca was incised along the line using No. 10 scalpel.\u003c/p\u003e \u003cp\u003eThe mucosal layer and the periosteal layer were dissected until the infraorbital foramen, then the infraorbital nerve were seen by using the periosteal rugine (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). The dissection was extended to get enough exposure of the anterior maxillary wall, then a self retaining retractor was placed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Since the mucosal layer was very fragile, dissection and placing the retractor was carefully done.\u003c/p\u003e \u003cp\u003eSublabial anterior antrostomy made with Caldwell-Luc procedure. A maxillotomy approximately 2x3 cm in size was performed in the anterior maxillary wall by using the high-speed drill (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). The infraorbital foramen made the superior border of the craniotomy to protect the neurovascular structures. After entering the maxillary sinus, the lateral and medial borders were extended to the transition points of the anterior maxillary sinus wall into the lateral and medial walls of the maxillary sinus. The base of the maxillary sinus was preserved as the inferior border to avoid damaging the anterior superior alveolar nerve (ASAN), middle superior alveolar nerve (MSON, and branches of the infraorbital nerve (ION) which receives sensory input from upper teeth.\u003c/p\u003e \u003cp\u003e \u003cb\u003e2. Maxillary Sinusoidal Stage\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWith the entrance to the maxillary sin\u0026uuml;s, the endoscopic stage was initiated (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). As a first step of the maxillary sinusoidal stage, the mucosal lining was removed to reveal the anatomical landmarks (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Medially, maxillary ostium which opens into the midlle meatus, as well as the infraorbital nerve and infraorbital artery extending from the posterior wall to the superior wall were identified. Laterally apex of the maxillary sinus was observed. The most critical part of this stage is preserving the inferior orbital wall while drilling the posterior maxillary wall.\u003c/p\u003e \u003cp\u003eSuperior boundary during the drilling process of the posterior maxillary wall is the finishing line of the orbital prominence. The anatomical landmarks of this stage are the infraorbital nerve (ION) and the infraorbital artery (IOA).\u003c/p\u003e \u003cp\u003ePosterior maxillary wall, medial to the ION and inferior to the orbital prominence, was drilled. Then, a window was opened through the posterior maxillary wall while preserving the neurovascular and muscular structures. At this stage, it is possible to widen this opening by using the Kerrison roungeur to get appropriate exposure.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3. Postmaxillary Sinusoidal Stage\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThrough the opening of the posterior maxillary wall, infratemporal fossa and pterygoid fossa were identified. Main anatomical landmark of this stage is the ION. Via following the ION, maxillary sinus and foramen rotundum were seen and this region was very rich in neurovascular and muscular structures (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Laterally, temporal and medial pterygoid muscle, medially, sphenopalatine artery, posteriorly, superior head of lateral pterygoid muscle which inserted to the infratemporal crest, inferiorly, superior head of lateral pterygoid muscle were seen. At this stage, lateral ptergygoid lamina can be drilled more, however the drilling of the medial pterygoid lamina is not within safe limits. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eVidian canal and the vidian nerve were located posteriorly to the sphenopalatine artery and foramen. In this region, sphenopalatine artery lying medial to the pterygomaxillary fissure, goes into the nasal cavity and suppliess the nasal septum.\u003c/p\u003e \u003cp\u003eOpening a window to the middle fossa necessitates sacrification of the superior head of the lateral pterygoid muscle originating from the infratemporal crest and inserting on the temporomandibular joint capsule and disc. Inferior head of the lateral pterygoid muscle, which originates from the lateral pterygoid lamina of the sphenoid bone and make insertion to the mandibular pterygoid fovea, was incised starting from the infratemporal crest to visualize the greater wing of the sphenoid bone. The bony window reaching the middle cranial fossa is through the greater wing of the sphenoid bone.\u003c/p\u003e \u003cp\u003eExternal carotid artery gives rise to the superficial temporal artery and the maxillary artery branches just posterior to the mandible. The maxillary artery enters the infratemporal fossa supplying the structures within the infratemporal fossa, the pterygoid fossa, dura mater, teeth, pharynx and nasal septum.\u003c/p\u003e \u003cp\u003eThe most important step of this stage is to determine the boundaries of the rectangle opening to the middle cranial fossa, and definition of the foramen ovale and the foramen rotundum is crucial (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). At this stage, the endoscope\u0026rsquo;s ability to provide a panoramic view offers an advantage in identifying these two foramina by enhancing spatial awareness and control. To define the foramen rotundum, proximal ION should be followed where maxillary nerve (V2) is visualized. Once defining the V2, endoscope is directed inferolaterally to reach the exit of the mandibular nerve (V3) which is the FO (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). It is crucial to keep in mind during drilling that V2-V3 junction is located between the FO and FR. Firstly, the vertical imaginary line passing through the foramen rotundum and the horizontal imaginary line passing through the foramen ovale were drawn. The safest quadrant is the superolateral quadrant, since this region meets the greater wing of the sphenoid bone (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAfter drilling the superolateral quadrant of the greater wing of the sphenoid bone, the dura of the anterior temporal pole was visualized (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). To get greater visualization angle, pivot of the endoscope was moved distally. From this point on, dural incision can be planned according the lesion.\u003c/p\u003e \u003cp\u003eAfter dural incision, anterior temporal pole parenchyma was visualized, and medial to the anterior temporal pole, Meckel\u0026rsquo;s cave, petrous apex and the cavernous sinus can be exposed (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB).\u003c/p\u003e"},{"header":"Methods \u0026 Materials","content":"\u003cp\u003eThis study was conducted at the laboratory between September and October 2021. Twelve formalin fixed cadaveric hemispheres in which the arteris were perfused with red and the veins with blue silicone were used for his study. Phases of macroscopic and microscopic dissections were photographed using the Canon EOS 550D with 18–55 mm and 100 mm macro lenses while endoscopic phases were captured vith 4K Storz and Richard-Wolf Logic 4K Endoscope system. Microscopic dissections were performed under the Carl Zeiss (AG, Oberkochen, Germany) and combined with the endoscope (4K Storz and Richard-Wolf Logic 4K Endoscope system). Between the dissections cadaveric specimens were preserved in %70 alcohol solution at room temperature.\u003c/p\u003e\u003cp\u003eSpecimens were supine positioned as in the surgical position. Dissections were performed in three stages; premaxillary sinusoidal, maxillary sinusoidal, and postmaxillary sinusoidal stages respectively.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eEndoscopic dissections were categorized into three stages; premaxillary sinusoidal, maxillary sinusoidal, and post maxillary sinusoidal stages respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e1. Premaxillary Sinusoidal Stage\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe head was positioned in a neutral supine position and secured to the Mayfield head clamp parallel to the horizontal plane as a simulation of the surgery. Upper lip was retracted macroscopically using suspensory sutures (Figure 1A). Then, incision line in dentogingival sulcus was aligned to correspond with the projection of the vestibulum oris between the left canine tooth and second molar tooth (Figure 1B). Due to fragility of mucosal tissue in cadaveric specimens, special care has been taken during retractor placement. The musoca was incised along the line using No. 10 scalpel.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mucosal layer and the periosteal layer were dissected until the infraorbital foramen, then the infraorbital nerve were seen by using the periosteal rugine (Figure 1C). The dissection was extended to get enough exposure of the anterior maxillary wall, then a self retaining retractor was placed (Figure 1C). Since the mucosal layer was very fragile, dissection and placing the retractor was carefully done.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSublabial anterior antrostomy made with Caldwell-Luc procedure. A maxillotomy approximately 2x3 cm in size was performed in the anterior maxillary wall by using the high-speed drill (Figure 1D). The infraorbital foramen made the superior border of the craniotomy to protect the neurovascular structures. After entering the maxillary sinus, the lateral and medial borders were extended to the transition points of the anterior maxillary sinus wall into the lateral and medial walls of the maxillary sinus. The base of the maxillary sinus was preserved as the inferior border to avoid damaging the anterior superior alveolar nerve (ASAN), middle superior alveolar nerve (MSON, and branches of the infraorbital nerve (ION) which receives sensory input from upper teeth.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2. Maxillary Sinusoidal Stage\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWith the entrance to the maxillary sin\u0026uuml;s, the endoscopic stage was initiated (Figure 2A). As a first step of the maxillary sinusoidal stage, the mucosal lining was removed to reveal the anatomical landmarks (Figure 2B). Medially, maxillary ostium which opens into the midlle meatus, as well as the infraorbital nerve and infraorbital artery extending from the posterior wall to the superior wall were identified. Laterally apex of the maxillary sinus was observed. The most critical part of this stage is preserving the inferior orbital wall while drilling the posterior maxillary wall.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSuperior boundary during the drilling process of the posterior maxillary wall is the finishing line of the orbital prominence. \u0026nbsp;The anatomical landmarks of this stage are the infraorbital nerve (ION) and the infraorbital artery (IOA).\u003c/p\u003e\n\u003cp\u003ePosterior maxillary wall, medial to the ION and inferior to the orbital prominence, was drilled. Then, a window was opened through the posterior maxillary wall while preserving the neurovascular and muscular structures. At this stage, it is possible to widen this opening by using the Kerrison roungeur to get appropriate exposure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3. Postmaxillary Sinusoidal Stage\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThrough the opening of the posterior maxillary wall, infratemporal fossa and pterygoid fossa were identified. Main anatomical landmark of this stage is the ION. Via following the ION, maxillary sinus and foramen rotundum were seen and this region was very rich in neurovascular and muscular structures (Figure 3A). Laterally, temporal and medial pterygoid muscle, medially, sphenopalatine artery, posteriorly, superior head of lateral pterygoid muscle which inserted to the infratemporal crest, inferiorly, superior head of lateral pterygoid muscle were seen. At this stage, lateral ptergygoid lamina can be drilled more, however the drilling of the medial pterygoid lamina is not within safe limits. (Figure 3B).\u003c/p\u003e\n\u003cp\u003eVidian canal and the vidian nerve were located posteriorly to the sphenopalatine artery and foramen. In this region, sphenopalatine artery lying medial to the pterygomaxillary fissure, goes into the nasal cavity and suppliess the nasal septum.\u003c/p\u003e\n\u003cp\u003eOpening a window to the middle fossa necessitates sacrification of the superior head of the lateral pterygoid muscle originating from the infratemporal crest and inserting on the temporomandibular joint capsule and disc. Inferior head of the lateral pterygoid muscle, which originates from the lateral pterygoid lamina of the sphenoid bone and make insertion to the mandibular pterygoid fovea, was incised starting from the infratemporal crest to visualize the greater wing of the sphenoid bone. The bony window reaching the middle cranial fossa is through the greater wing of the sphenoid bone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExternal carotid artery gives rise to the superficial temporal artery and the maxillary artery branches just posterior to the mandible. The maxillary artery enters the infratemporal fossa supplying the structures within the infratemporal fossa, the pterygoid fossa, dura mater, teeth, pharynx and nasal septum.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most important step of this stage is to determine the boundaries of the rectangle opening to the middle cranial fossa, and definition of the foramen ovale and the foramen rotundum is crucial (Figure 4A). At this stage, the endoscope\u0026rsquo;s ability to provide a\u0026nbsp;panoramic view\u0026nbsp;offers an advantage in identifying these two foramina by enhancing spatial awareness and control. To define the foramen rotundum, proximal ION should be followed where maxillary nerve (V2) is visualized. Once defining the V2, endoscope is directed inferolaterally to reach the exit of the mandibular nerve (V3) which is the FO (Figure 4). It is crucial to keep in mind during drilling that V2-V3 junction is located between the FO and FR. Firstly, the vertical imaginary line passing through the foramen rotundum and the horizontal imaginary line passing through the foramen ovale were drawn. The safest quadrant is the superolateral quadrant, since this region meets the greater wing of the sphenoid bone (Figure 4).\u003c/p\u003e\n\u003cp\u003eAfter drilling the superolateral quadrant of the greater wing of the sphenoid bone, the dura of the anterior temporal pole was visualized (Figure 5A). To get greater visualization angle, pivot of the endoscope was moved distally. From this point on, dural incision can be planned according the lesion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter dural incision, anterior temporal pole parenchyma was visualized, and medial to the anterior temporal pole, Meckel\u0026rsquo;s cave, petrous apex and the cavernous sinus can be exposed (Figure 5B).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMiddle cranial fossa lesions can be accessed through the transcranial approaches that have been used in neurosurgical practice for years. Moreover, with increasing use of endoscopy in skull base surgery, novel techniques have been defined.\u003c/p\u003e \u003cp\u003eRostral middle cranial fossa lesions can be reached by transcranial routes, such as subtemporal, pterional and orbitozygomatic approaches. However, especially with the subtemporal approach, reaching the rostral middle cranial fossa requires retraction of the anterior temporal lobe. Additionally, temporal muscle is incised and elevated to perform temporal craniotomy which may lead atrophy of the temporal muscle causing decline in the patient\u0026rsquo;s quality of life.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn addition to these, the paramedian supracerebellar-transtentorial approach, described by T\u0026uuml;re et al. is also among the alternative methods to reach the anterior temporal pole. The approach we have defined and this approach align linearly in the same plane, complementing each other.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn addition to transcranial approaches many approaches have been defined to reach the sphenoidal rostrum and even the Meckel\u0026rsquo;s cave.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] It is possible to reach the Meckel\u0026rsquo;s cave both endoscopically and microscopically. Among them, anterior (sublabial transmaxillary transpterygoid) and anteromedial (endoscopic endonasal transpterygoid transsphenoidal) approaches can be counted.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Furthermore, endoscopic endonasal, transoral sublabial, and transorbital methods have been used to access the infratemporal fossa.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe endoscopic endonasal transmaxillary transpterygoid approach has been used to reach middle cranial fossa lesions and offers a minimally invasive route to pterygopalatine fossa, infratemporal fossa, sphenoid sinus, cavernous sinus, petrous apex, and the Meckel\u0026rsquo;s cave.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] With this approach sphenopalatine artery is cauterized and transected, the palatine bone is drilled, then the lateral recess of the sphenoid sinus and pterygopalatine fossa was exposed.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] It is possible to reach the anterior fossa to the odontoid process in sagittal plane, and both foramen ovale in coronal plane via pure endoscopic endonasal approaches.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTransoral sublabial approach to maxillary sinuses was first described by George Caldwell of the U.S.A and Henri Luc of France in 19th century, during the pre-endoscopic era, to treat medically resistant maxillary sinusitis.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] With time, it has been used to access pathologies in maxillary sinus, orbital floor, pterygopalatine fossa and infratemporal fossa pathologies.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] Couldwell et al. extended sublabial transmaxillary approach to the anterior cavernous sinus by enlarging the superomedial border of the foramen rotundum.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Later, Gady Har-el defined a combined endoscopic transmaxillary and transnasal approach to the pterygoid region, lateral sphenoid sinus, and retrobulbar orbit.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePrevious studies have demonstrated that the sublabial transmaxillary transpterygoid approach to Meckel\u0026rsquo;s cave and the middle cranial fossa allows better exposure in the sagittal plane compared to the endoscopic endonasal approaches.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Furthermore, while accessing the foramen ovale and rotundum, sublabial endoscopic approaches offers superiority over endoscopic endonasal approaches in terms of surgical field of view and surgical comfort. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eEndonasal and sublabial endoscopic transmaxillary approaches can be combined to access the pterygopalatine fossa and orbital apex. Endonasal approach provides limited lateral exposure to the pterygopalatine fossa and infratemporal fossa, because it is limited by the nasal septum, nasolacrimal duct and pterygoid plates.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] Better exposure with endonasal route requires ethmoidectomy and sphenoidotomy or an inferior turbinectomy which may lead to different complications.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Therefore, better exposure can be obtained with combining endonasal approach with the sublabial approach which is not limited by the nasal septum and nasolacrimal duct.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eKassam et al., described an expanded endonasal approach for the middle cranial fossa and infratemporal fossa.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] This approach requires endoscopic middle turbinectomy with the use of 45\u0026ndash;70 degree endoscope which increases technical difficulty and the risk of complications.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTruong and Sun et al. described the sublabial transmaxillary transalisphenoidal approach to the middle cranial fossa and Meckel\u0026rsquo;s cave in their anatomic study with two cases. In this approach, after sublabial incision, the foramen rotundum, foramen ovale and the infraorbital nerve are defined endoscopically, then the greater wing of the sphenoid is drilled to expose the anterior dural wall of middle fossa and Meckel\u0026rsquo;s cave.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIt has been stated that the least invasive approach to treat trigeminal nerve pathologies such as squamous cell carcinoma, basal cell carcinoma, melanomas and adenoid cystic carcinomas is the endoscopic transmaxillary approach.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] DeMonte et al., described the microneurosurgical way of approach to the malignant maxillary nerve tumor with perineuroal extension, and they suggest the use of endoscope due to its advantages. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the literature, the sublabial transatral approaches have been reported to have certain advantages over the endonasal endoscopic approaches; 1) the use of endoscopes with angles greater than 30 degrees is not required 2) nerves within the pterygopalatine fossa, including the maxillary nerve, vidian nerve, and pterygopalatine ganglion, are not manipulated 3) it allows for easier exposure of the compartments lateral to the pterygopalatine fossa (sphenoidal rostrum, infratemporal fossa). [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOng et al. listed the potential complications of the endoscopic sublabial transmaxillary transpterygoid approach to middle cranial fossa as; complications related to the sublabial incision and maxillotomies, damage to the retromaxillary neurovascular structures, some chewing problems due to manipulation of the lateral pterygoid muscles, and cerebrospinal fluid fistula.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] As a result, facial anesthesia/dysesthesia, dental anesthesia, oroantral fistula can be seen.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Moreover, proper repair may be necessary not to have cerebrospinal fluid fistula.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Furthermore, fat graft fixation techiques can be applied as explained by Luzzi et al.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eYağmurlu et al., described the sublabial transmaxillary approach to Meckel\u0026rsquo;s cave in their cadaveric study.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] It was stated that this approach provides extradural access to lateral portion of the Meckel\u0026rsquo;s cave with great visualization for selected cases.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] The maxillary artery is sacrificed to make lateral pterygoid muscle free in this approach.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] The boundaries of the craniectomy defined as; starts at foramen rotundum, proceeds in a 6 to 12 o\u0026rsquo;clock direction to the foramen ovale laterally.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Superior boundary is the upper head of the lateral pterygoid muscle and the inferior boundary is the imaginary line drawn between the lowermost edges of the foramen ovale and the foramen rotundum.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Foramen ovale is drilled superolateraly to protect the eustachian tube.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTheodosopoulos et al. reach the infratemporal fossa combining Caldwell-Luc and endonasal transmaxillary approaches.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Thus, they expanded the boundaries of both approaches, providing exposure to even middle meningeal artery and the upper cervical carotid artery.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWhile endonasal approaches are more appropriate for lesions in the medial nasal cavity and medial orbit, the sublabial approaches offer better exposure for lateral middle cranial fossa lesions. In some instances, two approaches can be combined.\u003c/p\u003e \u003cp\u003eIn our cadaveric study, we demonstrated that the transmaxillary middle fossa approach with sublabial incision resulted in minimal brain parenchyma retraction. Furthermore, since our approach is performed mainly via the sublabial incision, with no incison on the temporal muscle, the risk of temporal muscle atrophy and related cosmetic issues won\u0026rsquo;t be consideration. During the dissections, after the maxillotomy, lateral to the branches of the maxillary artery and the branches of the maxillary nerve was exposed like previous studies. During dissections, angled endoscopes were not used since straight endoscopes provides excellent exposure. With this approach beside having the excellent view of the lateral infratemporal fossa, possible maxillary artery injuries can be controlled over.\u003c/p\u003e \u003cp\u003eIn addition to those, the safe zone was identified according to the main anatomical landmarks. Since the anatomy of the middle cranial fossa and the endoscopic routes reaching there comprise a complex anatomy, we aimed to define the craniectomy borders in a more simple way by using two prominent structures; foramen ovale and foramen rotundum. In this way, we aimed a safe surgical corridor which allowing enough exposure. The volume of maxillary sinus forms a natural corridor leading to the retromaxillary space allowing for free movement of surgical instruments. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Furthermore, in the endonasal approach, the sphenopalatine artery, which needs to be transected for the middle fossa approach, has been freely exposed and preserved in this approach.\u003c/p\u003e \u003cp\u003eIn the middle cranial fossa approaches, the most suitable approach is determined based on the location of the lesion and the desired angle of attack. A deep understanding of the gross and endoscopic anatomy of the pterygopalatine and infratemporal fossa is crucial for this approach like other approaches to the skull base. With detailed description of the anatomical landmarks and the boundaries of the maxillotomy in this study, the middle cranial fossa can be accessed safely using the sublabial transmaxillary approach, which provides the necessary exposure.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eETTAMCF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eendoscopic transmaxillary transpterygoidal approach to the middle cranial fossa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eASAN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eanterior superior alveolar nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMSON\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emiddle superior alveolar nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eION\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einfraorbital nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIOA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe infraorbital artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eV2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emaxillary nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eV3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emandibular nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eThis study was performed inaccordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted with the approval of the Başakşehir \u0026Ccedil;am and Sakura City Hospital Clinical Research Ethics Committee, dated September 8, 2021, with protocol number 2021-201, confirming its ethical and regulatory compliance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe manuscript does not contain clinical studies or patient data.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026rsquo; and/or \u0026lsquo;Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests and Funding:\u0026nbsp;\u003c/strong\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEmployment:\u0026nbsp;\u003c/strong\u003eThe authors have no recent, current, or anticipated employment with any organization that may gain or lose financially through the publication of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Interests:\u0026nbsp;\u003c/strong\u003eThe authors declare they have no financial interests. No funding was received to assist with the preparation of this manuscript. No funding was received for conducting this study. No funds, grants, or other support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNon-Financial Interests\u003c/strong\u003e: The authors declare no non-financial interests that could influence the interpretation or presentation of the data, such as advisory roles, editorial positions, mentoring relations, or personal beliefs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information:\u0026nbsp;\u003c/strong\u003eThis study was conducted at Prof. Rhoton Applied Anatomy and Surgical Training Center, Bah\u0026ccedil;eşehir University School of Medicine. We certify that the content of this manuscript, in part or in full, has not been submitted to any other journal in any form, and its publication has been approved by all co-authors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e All authors contributed to the study conception and design. \u003cstrong\u003eConceptualization:\u0026nbsp;\u003c/strong\u003eEbubekir Akpınar,Hasan \u0026Ccedil;ağrı Postuk\u003cstrong\u003e; Methodology:\u0026nbsp;\u003c/strong\u003eAysu İyig\u0026uuml;n Kabakcı, Ebubekir Akpınar\u003cstrong\u003e; Formal analysis and investigation:\u0026nbsp;\u003c/strong\u003eErcan Boşnak, Hasan \u0026Ccedil;ağrı Postuk\u003cstrong\u003e; Writing - original draft preparation:\u0026nbsp;\u003c/strong\u003eAysu İyig\u0026uuml;n Kabakcı, Ebubekir Akpınar\u003cstrong\u003e; Writing - review and editing:\u0026nbsp;\u003c/strong\u003eAbuzer G\u0026uuml;ng\u0026ouml;r, Akın Akakın\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003eErcan Boşnak\u003cstrong\u003e; Supervision:\u0026nbsp;\u003c/strong\u003eAbuzer G\u0026uuml;ng\u0026ouml;r, Bekir Tuğcu, T\u0026uuml;rker Kılı\u0026ccedil;,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlimohamadi M, Hajiabadi M, Gerganov V, Fahlbusch R, Samii M (2015) Combined endonasal and sublabial endoscopic transmaxillary approach to the pterygopalatine fossa and orbital apex. Acta Neurochir (Wien) 157(6):919\u0026ndash;929\u003c/li\u003e\n\u003cli\u003eAmit M, Eran A, Billan S, Fridman E, Na\u0026rsquo;ara S, Charas T, Gil Z (2016) Perineural Spread in Noncutaneous Head and Neck Cancer: New Insights into an Old Problem. J Neurol Surg B Skull Base 77(2):86\u0026ndash;95\u003c/li\u003e\n\u003cli\u003eCouldwell WT, Sabit I, Weiss MH, Giannotta SL, Rice D (1997) Transmaxillary approach to the anterior cavernous sinus: a microanatomic study. Neurosurgery 40(6):1307\u0026ndash;1311\u003c/li\u003e\n\u003cli\u003eDeMonte F, Hanna E (2007) Transmaxillary exploration of the intracranial portion of the maxillary nerve in malignant perineural disease: Technical note. J Neurosurg 107(3):672\u0026ndash;677\u003c/li\u003e\n\u003cli\u003eElhadi AM, Almefty KK, Mendes GAC, Kalani MYS, Nakaji P, Dru A, Preul MC, Little AS (2014) Comparison of Surgical Freedom and Area of Exposure in Three Endoscopic Transmaxillary Approaches to the Anterolateral Cranial Base. J Neurol Surg B Skull Base 75(5):346\u0026ndash;353\u003c/li\u003e\n\u003cli\u003eElhadi AM, Zaidi HA, Yagmurlu K, Ahmed S, Rhoton AL, Nakaji P, Preul MC, Little AS (2016) Infraorbital nerve: A surgically relevant landmark for the pterygopalatine fossa, cavernous sinus, and anterolateral skull base in endoscopic transmaxillary approaches. J Neurosurg 125(6):1460\u0026ndash;1468\u003c/li\u003e\n\u003cli\u003eHadad G, Bassagasteguy L, Carrau RL, Mataza JC, Kassam A, Snyderman CH, Mintz A (2006) A novel reconstructive technique after endoscopic expanded endonasal approaches: Vascular pedicle nasoseptal flap. Laryngoscope 116(10):1882\u0026ndash;1886\u003c/li\u003e\n\u003cli\u003eHofstetter CP, Singh A, Anand VK, Kacker A, Schwartz TH (2010) The endoscopic, endonasal, transmaxillary transpterygoid approach to the pterygopalatine fossa, infratemporal fossa, petrous apex, and the Meckel cave. J Neurosurg 113(5):967\u0026ndash;974\u003c/li\u003e\n\u003cli\u003eLin BJ, Ju DT, Hsu TH, et al (2019) Endoscopic transorbital approach to anterolateral skull base through inferior orbital fissure: a cadaveric study. Acta Neurochir (Wien) 161(9):1919\u0026ndash;1929\u003c/li\u003e\n\u003cli\u003eLuzzi S, Doğruel Y, G\u0026uuml;ng\u0026ouml;r A, Gurses ME, Rahmanov S, T\u0026uuml;re H, T\u0026uuml;re U (2025) Clival dural reconstruction via transnasal approaches: fat graft fixation technique. Neurosurg Focus 58(2):E4\u003c/li\u003e\n\u003cli\u003eMart\u0026iacute;nez-P\u0026eacute;rez R, Zachariah M, Li R, Silveira-Bertazzo G, Carrau RL, Prevedello DM (2020) Expanded endoscopic endonasal transpterygoid transmaxillary approach for a giant trigeminal schwannoma. Neurosurgical Focus: Video. doi: 10.3171/2020.4.FocusVid.19904\u003c/li\u003e\n\u003cli\u003eNitzan DW, Constantini S (1992) Severe limitation in mouth opening following transtemporal neurosurgical procedures: diagnosis, treatment, and prevention.\u003c/li\u003e\n\u003cli\u003eOng BC, Gore PA, Donnellan MB, Kertesz T, Teo C (2008) Surgical Approach. OPERATIVE NEUROSURGERY. doi: 10.1227/01.NEU.0000297050.89658.61\u003c/li\u003e\n\u003cli\u003ePrevedello DM, Doglietto F, Jane JA, Jagannathan J, Han J, Laws ER (2007) History of endoscopic skull base surgery: Its evolution and current reality. J Neurosurg 107(1):206\u0026ndash;213\u003c/li\u003e\n\u003cli\u003eVan Rompaey J, Suruliraj A, Carrau R, Panizza B, Solares CA (2014) Meckel\u0026rsquo;s cave access: Anatomic study comparing the endoscopic transantral and endonasal approaches. European Archives of Oto-Rhino-Laryngology 271(4):787\u0026ndash;794\u003c/li\u003e\n\u003cli\u003eSingh FM, Mak SY, Bonington SC (2015) Patterns of spread of head and neck adenoid cystic carcinoma. Clin Radiol 70(6):644\u0026ndash;653\u003c/li\u003e\n\u003cli\u003eTheodosopoulos P V., Guthikonda B, Brescia A, Keller JT, Zimmer LA (2010) Endoscopic approach to the infratemporal fossa: Anatomic study. Neurosurgery 66(1):196\u0026ndash;202\u003c/li\u003e\n\u003cli\u003eTruong HQ, Sun X, Celtikci E, Borghei-Razavi H, Wang EW, Snyderman CH, Gardner PA, Fernandez-Miranda JC (2019) Endoscopic anterior transmaxillary \u0026ldquo;transalisphenoid\u0026rdquo; approach to Meckel\u0026rsquo;s cave and the middle cranial fossa: An anatomical study and clinical application. J Neurosurg 130(1):227\u0026ndash;237\u003c/li\u003e\n\u003cli\u003eT\u0026uuml;re U, Harput MV, Kaya AH, Baimedi P, Firat Z, T\u0026uuml;re H, Bing\u0026ouml;l CA (2012) The paramedian supracerebellar-transtentorial approach to the entire length of the mediobasal temporal region: An anatomical and clinical study - Laboratory investigation. J Neurosurg 116(4):773\u0026ndash;791\u003c/li\u003e\n\u003cli\u003eWang X, Zhang X, Hu F, Yu Y, Gu Y, Xie T, Ge J (2016) Image-guided endoscopic endonasal transmaxillary transpterygoid approach to Meckel\u0026rsquo;s cave. Turk Neurosurg 26(2):309\u0026ndash;314\u003c/li\u003e\n\u003cli\u003eWarren TA, Nagle CM, Bowman J, Panizza BJ (2016) The Natural History and Treatment Outcomes of Perineural Spread of Malignancy within the Head and Neck. J Neurol Surg B Skull Base 77(2):107\u0026ndash;112\u003c/li\u003e\n\u003cli\u003eWilson DA, Williamson RW, Preul MC, Little AS (2014) Comparative analysis of surgical freedom and angle of attack of two minimal-access endoscopic transmaxillary approaches to the anterolateral skull base. World Neurosurg 82(3):E487\u0026ndash;E493\u003c/li\u003e\n\u003cli\u003eYağmurlu K, Mooney MA, Almefty KK, Bozkurt B, Tanrı\u0026ouml;ver N, Little AS, Preul MC (2018) An Alternative Endoscopic Anterolateral Route to Meckel\u0026rsquo;s Cave: An Anatomic Feasibility Study Using a Sublabial Transmaxillary Approach. World Neurosurg 114:134\u0026ndash;141\u003c/li\u003e\n\u003cli\u003eAndrade, F. C. d., FILHO, C. M. D. A., \u0026amp; FILHO, J. C. (1998). Dysfunction of the temporalis muscle after pterional craniotomy for intracranial aneurysms: comparative, prospective and randomized study of one flap versus two flaps dieresis. Arquivos De Neuro-Psiquiatria, 56(2), 200-205. https://doi.org/10.1590/s0004-282x1998000200006.\u003c/li\u003e\n\u003cli\u003eKassam, A. B., Gardner, P., Snyderman, C., Mintz, A., \u0026amp; Carrau, R. (2005). Expanded endonasal approach: fully endoscopic, completely transnasal approach to the middle third of the clivus, petrous bone, middle cranial fossa, and infratemporal fossa. Neurosurgical focus, 19(1), E6.\u003c/li\u003e\n\u003cli\u003eCavallo, L. M., Messina, A., Gardner, P., Esposito, F., Kassam, A. B., Cappabianca, P., de Divitiis, E., \u0026amp; Tschabitscher, M. (2005). Extended endoscopic endonasal approach to the pterygopalatine fossa: anatomical study and clinical considerations. Neurosurgical focus, 19(1), E5.\u003c/li\u003e\n\u003cli\u003eTabari, A., Nasirmohtaram, S., Mohammadi, H. R., Zeinalizadeh, M., \u0026amp; Sadrehosseini, S. M. (2024). Anterior endoscopic sublabial transmaxillary access to middle cranial base lesions. Head \u0026amp; neck, 46(5), 1028\u0026ndash;1042. https://doi.org/10.1002/hed.27725\u003c/li\u003e\n\u003cli\u003eSchwartz, T. H., Fraser, J. F., Brown, S., Tabaee, A., Kacker, A., \u0026amp; Anand, V. K. (2008). Endoscopic cranial base surgery: classification of operative approaches. Neurosurgery, 62(5), 991\u0026ndash;1005. https://doi.org/10.1227/01.neu.0000325861.06832.06\u003c/li\u003e\n\u003cli\u003eMacbeth R. (1971). Caldwell, Luc, and their operation. The Laryngoscope, 81(10), 1652\u0026ndash;1657. https://doi.org/10.1288/00005537-197110000-00011\u003c/li\u003e\n\u003cli\u003eMatheny, K. E., \u0026amp; Duncavage, J. A. (2003). Contemporary indications for the Caldwell-Luc procedure. Current opinion in otolaryngology \u0026amp; head and neck surgery, 11(1), 23\u0026ndash;26. https://doi.org/10.1097/00020840-200302000-00005\u003c/li\u003e\n\u003cli\u003eHar-El G. (2005). Combined endoscopic transmaxillary-transnasal approach to the pterygoid region, lateral sphenoid sinus, and retrobulbar orbit. The Annals of otology, rhinology, and laryngology, 114(6), 439\u0026ndash;442. https://doi.org/10.1177/000348940511400605\u003c/li\u003e\n\u003cli\u003eHar-El G. (2005). Combined endoscopic transmaxillary-transnasal approach to the pterygoid region, lateral sphenoid sinus, and retrobulbar orbit. The Annals of otology, rhinology, and laryngology, 114(6), 439\u0026ndash;442. https://doi.org/10.1177/000348940511400605\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"endoscopic sublabial approach, middle cranial fossa, skull base, transmaxillary approach","lastPublishedDoi":"10.21203/rs.3.rs-6795600/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6795600/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAlmost all approaches to middle cranial fossa pathologies are performed with transcranial approaches. Studies on the endoscopic approach to this region are gaining popularity over time. In this study, we aimed to demonstrate the anatomical framework of the endoscopic transmaxillary transpterygoidal approach to the middle cranial fossa (ETTAMCF).\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eSix formalin fixed red and blue silicon injected human cadaveric heads were used for endoscopic dissections to define surgical landmarks and limits of the ETTAMCF. Photos were taken with 4K high-definition camera and video monitor endoscopy systems.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTo reach middle cranial fossa via ETTAMCF includes; A bucco-gingival sulcus insicion, mucosal dissection, drilling maxillary sinus anterior wall (limited superiorly with infraorbital foramen, inferiorly with buccogingival sulcus), removing mucosa of maxillary sinus while preserving infraorbital nerve, opening posterior wall of the maxillary sinus (limited medialy with infraorbital nerve), drilling pterygoid process, mobilize and retracting the upper head of lateral pterygoid muscle and temporal muscle, definition foramen rotundum and foramen ovale with following maxillary nerve and mandibular nerve, drilling sphenoid bone (limited medially with vertical line from foramen ovale inferiorly with horizontal line from foramen rotundum) and reaching temporal lobe anterior pole with opening dura mater.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTemporal lobe anterior pole is accessible safely via transmaxillary transpterygoideal approach by using endoscope while preserving neurovasculer structures. This approach provides safe access to the anterior temporal lobe without craniotomy and parenchyma retraction, as an alternative to transcranial approaches. We predict that surgery of anterior temporal lobe lesions, can be performed with this approach.\u003c/p\u003e","manuscriptTitle":"Defining the Safe Zone; the Endoscopic Sublabial Transmaxillary Approach to the Middle Cranial Fossa","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-09 08:38:24","doi":"10.21203/rs.3.rs-6795600/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6ad313aa-942e-4228-a13b-d5482f886092","owner":[],"postedDate":"June 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-10T13:23:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-09 08:38:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6795600","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6795600","identity":"rs-6795600","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}