Utilizing In-Situ Bone Flap for Skull Base Reconstruction in Endoscopic Surgery of Invasive Pituitary Adenoma: A Novel Approach

Utilizing In-Situ Bone Flap for Skull Base Reconstruction in Endoscopic Surgery of Invasive Pituitary Adenoma: A Novel Approach | 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 Utilizing In-Situ Bone Flap for Skull Base Reconstruction in Endoscopic Surgery of Invasive Pituitary Adenoma: A Novel Approach Jinlai Liu, Kaile Chen, Kuo Yu, Zhiyuan Liu, Kexiang Dai, Ke Xu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4334254/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 Objective: To evaluate the efficacy of in-situ bone flap (ISBF) repositioning technique in skull base reconstruction for invasive pituitary adenoma (IPA) via endoscopic endonasal approach (EEA). Method: In a retrospective study spanning the years 2018 to 2023, we investigated the efficacy of in-situ bone flap (ISBF) repositioning technique in patients with invasive pituitary adenoma (IPA) who underwent endoscopic endonasal surgery (EEA). Among the 115 patients included in the study, 65 were assigned to the group, while the remaining 55 were categorized into the non-ISBF group. Comprehensive data on patients’ basic characteristics, surgical situation, and clinical outcomes were meticulously collected and analyzed. Results: In our study, we observed postoperative cerebrospinal fluid (CSF) leakage in 1 out of 65 patients in the ISBF group, while 8 out of 50 patients in the non-ISBF group experienced this complication, indicating a significant difference (P<0.05). Conclusion: The ISBF repositioning technique emerges as an effective and feasible method for skull base reconstruction in patients who have underwent EEA surgery for IPA. Notably, this technique significantly reduces the incidence of postoperative CSF leakage. invasive aggressive skull base reconstruction pituitary adenoma endoscopic transsphenoidal CSF leakage in-situ bone flap rigid Figures Figure 1 Figure 2 Figure 3 Introduction Pituitary adenomas(PAs), ranking as the third most prevalent neurological tumors following gliomas and meningiomas, represent the predominant lesion within the sellar region.(1) Approximately 25% to 55% of pituitary adenomas manifest as invasive pituitary adenomas (IPAs; classified as Knosp III and IV). These IPAs are characterized by their invasion into adjacent tissues. Consequently, they are associated with a less favorable prognosis compared to their non-invasive counterparts.(2) The Endoscopic Endonasal Approach (EEA) has emerged as the preferred surgical method for pituitary adenoma due to its advantages such as enhanced visualization, minimization of brain injury and neurovascular retraction, and reduced postoperative hospitalization duration, etc.(3) For EEA surgery, the importance of effective skull base reconstruction and comprehensive lesion resection cannot be overstated.(4) Addressing the skull base defect after surgery has consistently posed significant challenges in EEA surgery for PAs. Given that IPAs are often larger in size and infiltrate adjacent tissues, they result in a more extensive skull base defect during endoscopic surgery. This can subsequently escalate the risk of postoperative complications, including CSF and meningitis.(5) There is a paucity of research specifically investigating efficacious methods for skull base reconstruction in EEA surgery of IPAs. Consequently, the exploration of an effective technique is of paramount importance. ISBF, characterized by the creation of a bone flap that can be subsequently repositioned and secured within its original location to repair a bony defect resulting from surgical procedures during EEA, has been proved effective in reducing the incidence of postoperative cerebrospinal fluid (CSF) leakage by several scholars.(6) However, the implication of this skull base reconstruction technique on patients with IPA remains ambiguous and necessitate additional exploration. Our research indicates that the technique of ISBF reconstruction of the skull base is a safe and effective strategy for patients with IPA who have undergone EEA surgery. Method Data collection and analysis: We retrospectively collected data on patients with intraoperative pathological diagnosis of pituitary adenomas who underwent EEA surgery from 2018 to 2023. Among them, patients with preoperative imaging grades Knosp III and IV were included in the study. There are 115 patients met the inclusion criteria. 65 of these patients were categorized in the ISBF group by applying the ISBF repositioning technique during the surgery, and the remaining 50 patients were categorized as the non-ISBF group. Patients’ characteristics, surgical situation and clinical outcomes were evaluated and reviewed. Surgical technique: Before proceeding with the surgery, the patient underwent a comprehensive series of tests to exclude any contraindications to endoscopic endonasal approach (EEA) surgery. Magnetic Resonance Imaging (MRI) was employed to quantify the tumor size and delineate the extent of tumor invasion into peripheral neurovascular structures, including the optic nerve (ON), internal carotid artery (ICA), and cavernous sinus (CS), third ventricle (TV), among others. This information is crucial for the strategic planning and execution of the surgical procedure. Additionally, Computed Tomography (CT) was utilized to assess bony structure of sellar region and sphenoidal sinus. Patients were intubated and positioned supine prior to the procedure. The surgical approach employed was the two-nostril/two-surgeon/four-hands technique, necessitating a posterior septectomy to enhance visualization. Throughout the surgery, the endoscope was secured to a pneumatic arm, providing a stable view and increased flexibility for the surgeon. Systematic preparation of the right thigh was undertaken for harvesting adipose tissue and fascia lata. To mitigate mucosal hemorrhage, the nasal cavity was packed with cottonoids soaked in adrenaline for 10 minutes. All patients received prophylactic antibiotics (cefuroxime sodium) 30 minutes before the incision. The anterior wall of sphenoidal sinus was carefully opened wide with microdrill with diamond burr to expose the sphenoidal sinus cavity and then sphenoid septation was removed with a Kerrison rongeur. During the process of accessing the pituitary fossa via the opening of the posterior wall of the sphenoidal sinus, an ISBF was harvested, in accordance with methods previously documented in the literature.(6) The coronal dimensions of the ISBF were typically confined between the bilateral ICA protuberances or between the bilateral optic protuberances. The sagittal dimensions of the bone flap were adjustable, contingent upon the location and size of the lesion. A high-speed micro drill was employed to perform an incision on the skull base bone along the dotted line demarcated in Fig1A, facilitating the extraction of the ISBF. After the incision, the bone flap was meticulously elevated from the dura mater (Fig1B). Throughout this procedure, it was imperative to preserve the integrity of the flap to mitigate the risk of inflicting damage to the adjacent tissues due to potential partial rupture and subsequent displacement of the flap following repositioning. Depending on the surgical requirements, the flap could either be folded to one side or temporarily excised via the nasal cavity. After the resection of the tumor, the skull base reconstruction was performed. Different reconstruction techniques were used for the ISBF group and non-ISBF group. In the non-ISBF group, a multilayer reconstruction was systematically employed. The first layer was constituted by adipose tissue, harvested from the patient’s thigh, which was then inserted into tumor cavity as an inlay graft. The subsequent layer was composed of the fascia lata, procured from an incision on the patient’s thigh, serving as an onlay graft. Finally, the synthetic dura was strategically positioned over the fascia lata graft, forming the third layer. Within the introduction of the ISBF repositioning technique, we adopted a distinct reconstruction strategy for the selected patients in the ISBF group. The first layer was constituted by adipose tissue obtained from thigh, which was filled into tumor cavity to eliminate the dead space (Fig2A). Subsequently, the harvested ISBF was repositioned to cover the bone defect, forming the second layer, which was different from the approach to skull base reconstruction in patients in the non-ISBF group (Fig2B). The third layer was composed of the fasica lata from thigh, covering the ISBF (Fig2C). Finally, the synthetic dura was applied to cover the fasica lata as the fourth layer (Fig2D). The surgeries were performed by an experienced surgeon (Prof. Peng Zhao) in the Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, thus minimizing the confounding factors brought by learning curve. (7) The prophylactic lumbar drainage was not routinely performed in the patients, because there is few evidence to support that adjunctive lumbar drainage significantly reduces the incidence of postoperative CSF leak. (8) Postoperative management: All patients underwent CT scan right after the surgery to determine if there was any postoperative intracranial hemorrhage. Following the surgical intervention, all patients underwent an enhanced MRI within a 48-hour period, aiming to ascertain the degree of tumor resection, evaluate the integrity of the skull base reconstruction, and assess potential damage inflicted upon the adjacent vascular and neural structures. All patients were subjected to a diagnostic ‘tilt test’ to identify the pressure of CSF rhinorrhea. During this test, patients were instructed to incline their head downward for 30 seconds. A persistent watery discharge from one or both nostrils typically signifies a failed repair resulting in CSF rhinorrhea. Conversely, a discharge resembling a thicker mucus-like substance does not indicate CSF rhinorrhea.(9) In addition, we conducted a series of chemical analyses, including the glucose oxidase assay and the β2-transferrin test, on the rhinorrhea samples collected from patients. These tests serve as valuable tools in the diagnostic process for CSF leakage.(10) Results Patient characteristics: The mean age of patients in the ISBF and non-ISBF groups was 52.13 and 51.90 years, respectively, with no significant difference observed (P = 0.264). The sex distribution across both groups was also statistically similar, with females constituting 47% (31/65) of the ISBF group and 58% (29/50) of the non-ISBF group (P = 0.273). In the non-ISBF group, two patients had a history of recurrent IPA and had previously been treated with EEA surgery. However, in the ISBF group, there were no cases of recurrent IPA. Statistical analysis revealed no significant difference between them (P = 0.364). The size of tumor, quantified as the maximum diameter derived from preoperative MRI, exhibited no significant disparity between the ISBF group (26.15 mm) and the non-ISBF group (29.67 mm) (P = 0.114). Furthermore, no significant differences were found between the ISBF and non-ISBF group in terms of medical history, including diabetes, hypertension, and coronary heart disease (CHD) (P = 0.686, 0.252, 1.00). The comparison of the Body Mass Index (BMI) between the two groups did not yield any statistically significant differences (P = 0.872). Lastly, the Knosp grade of each patient’s tumor was ascertained through preoperative enhanced MRI. Upon statistical analysis, the distribution of Knosp grades between the two groups did not demonstrate any significant disparity (P = 0.880). (Table1) Surgical situation Intraoperative CSF leakage was observed in 7 patients from the ISBF group and 8 patients from the non-ISBF group, yielding no statistically significant differences (P = 0.409). Notably, the mean operation time (OR time) for ISBF patients was 86 minutes, while the non-ISBF patients with a mean OR time of 98 minutes, with no significant disparity between the two groups (P = 0.144). (Table2) Clinical outcomes: Within the ISBF cohort, a singular instance of postoperative CSF leakage was observed (1/65, 1.53%), in contrast to the non-ISBF cohort where 8 instances were reported (8/50, 16%). This disparity in the incidence of CSF leakage between the two cohorts is statistically significant(P=0.012). The average length of postoperative hospitalization for patients within the ISBF group was 5.50 days, comparatively less than the 7.10 days noted in the non-ISBF group, despite this, the difference did not reach statistical significance (P=0.081). Postoperative polyuria was observed in 6 patients in the ISBF group (6 out of 65, 9.23%) and in 5 patients in the non-ISBF group (5 out of 50, 10%), with no significant differences noted. Two patients in the ISBF group developed postoperative meningitis (2 out of 65, 3.07%), compared to four patients in the non-ISBF group (4 out of 50, 8%). However, there was no statistical difference between the two groups (P=0.451). Lastly, none of the patients in either group experienced postoperative ON injury or ICA injury associated with ISBF harvesting and repositioning. (Table 3) Table1 patient characteristics : ISBF Non-ISBF P-value No of patients 65 50 Sex Male 34 21 0.273 Female 31 29 Age 52.13±14.199(years) 51.90±12.98(years) 0.246 Tumor size 26.15±9.40(mm) 29.67±11.90(mm) 0.114 BMI 24.92±4.69(kg/m 2 ) 25.77±3.68(kg/m 2 ) 0.872 Diabetes Yes No 5 58 6 44 0.686 Previous surgery Yes No 0 65 2 48 0.364 Radiotherapy history Yes No 0 65 0 50 — Hypertension Yes No 13 50 15 35 0.252 CHD Yes No 1 64 0 50 1.00 Knosp grade III IV 41 9 54 11 0.880 Table2 surgical situation: ISBF Non-ISBF P-value Intraoperative CSF leak Yes No 7 58 8 42 0.409 Operation time 86.35±33.79(min) 98.92±24.64(min) 0.144 Table3 clinical outcomes ISBF Non-ISBF P-value Postoperative CSF leakage Yes No 1 64 8 42 0.012 Postoperative epistaxis Yes No 1 64 0 50 1.00 Postoperative polyuria Yes No 6 59 5 45 1.00 Postoperative meningitis Yes No 2 63 4 46 0.451 Postoperative hospital stays 5.50±1.23(days) 7.10±1.84(days) 0.081 ICA injury — Yes No `0 65 0 50 ON injury Yes No 0 65 0 50 — Conclusion The repositioning of ISBF presents a dependable, expedient, and viable technique for skull base reconstruction in patients with IPA undergoing EEA surgery. Our preliminary study results indicate that the ISBF, when combined with a multilayer closure technique, significantly reduces the incidence of postoperative CSF leakage without increasing the occurrence of other complications. Discussion Pituitary adenomas, benign in nature, account for a significant proportion, specifically 10% to 15%, of intracranial neoplasms. Despite their benign classification, a subset of these adenomas exhibits aggressive clinical behaviors, including rapid proliferation, invasion of surrounding tissues and resistance to conventional treatment.(11) The treatment of IPAs presents significant challenges due to their propensity to invade adjacent structures, including the cavernous sinus, dura, ICAs, ONs, TV, etc. The Knosp grade system was proposed in 1993 to classify pituitary adenoma according to the tumor anatomical relationship between ICAs. Within this system, grades III, IV are designated as IPAs. (12) EEA surgery has become the first-line treatment for IPAs due to its advantages over microscopic surgery such as higher gross total resection (GTR) rate, more flexible maneuvering, better visualization, and better postoperative improvement of endocrine function, etc. (13, 14) Because IPAs invaded surrounding tissues, especially CS, the extended EEA approach was required to obtain better exposure and increase tumor resection rate. (15, 16) Previous studies noted that GTR of approximately 80% could be achieved utilizing extended EEA approach to remove IPAs, and high GTR rate tends to result in a better prognosis. (17, 18) The intraoperative assistance of Doppler ultrasound and magnetic neuronavigational system was essential to prevent damage to peripheral neurovascular structures during extended EEA surgery, especially the ICAs. (19, 20) Many scholars kept pushing the boundaries of indications for extended EEA approach. Certain distinct subtypes of pituitary adenomas such as dumbbell-shape tumors, pure suprasellar adenomas, fibrous adenomas, have historically proven refractory to conventional EEA surgery. However, these challenging cases can now be effectively addressed through the extended EEA approach. (21) The successful execution of EEA surgery for IPAs hinges on two critical factors: the comprehensive resection of the tumor and effective skull base reconstruction.(4) Patients who have undergone EEA surgery are susceptible to postoperative complications associated with skull base defects, including CSF leak and meningitis, which may prolong hospitalization and lead to repeated surgery. (22)Patients with IPA are more susceptible to postoperative CSF leaks compared to patients with non-IPA. This increased risk is attributed to the larger tumor volume and the skull base defects that occur during surgery. (23, 24) Consequently, it is imperative to investigate more effective strategies for skull base reconstruction in EEA surgery for IPAs. The multilayer construction technique, which employs a combination of autologous and synthetic materials, is a prevalent practice in clinical settings. This method encompasses the use of free autografts, intranasal vascularized flaps, synthetic dural replacement grafts, and pedicled nasoseptal flaps. (4, 25) However, it is important to note that these materials are not fully capable of repairing bony defects of the skull base. It has previously been suggested that rigid reconstruction of the skull base was unnecessary by some literature. (26) However, in recent years, an increasing number of scholars now advocate for a more affirmative stance regarding rigid reconstruction. Their rationale centers on the potential effectiveness of these procedures in mitigating complications associated with skull base defects, including acute or chronic headaches and pseudo meningoceles. (6) Various rigid reconstruction material has been explored and proposed recently, including bioabsorbable plate, hydroxyapatite cement, titanium mesh, autologous cartilage, etc. (27-30) Compared to these materials, ISBF has better histocompatibility, conforms better to the complex anatomy of the skull base, and has lower risk of infection and damage to adjacent tissues due to graft displacement. (31) Previous studies have demonstrated the effectiveness of applying ISBF for skull base reconstruction in EEA surgery. (31, 32) However, there are no studies exploring the role of ISBF in skull base reconstruction in EEA surgery for IPAs. Our investigation revealed that the ISBF technique was also effective in reducing the incidence of postoperative CSF leak in IPA patients. Throughout the course of our investigation, we observed that patients within the ISBF group exhibited minimal sellar floor subsidence, as evidenced by postoperative MRI. We postulated that a reduced degree of sellar floor subsidence could potentially mitigate the extent of pituitary stalk traction, thereby diminishing the incidence of postoperative polyuria. This hypothesis appears to align with the lower incidence of postoperative polyuria observed in ISBF group patients (10.16%) compared to those in non-ISBF group (11.11%), despite the lack of statistical significance (P>0.05). However, it is imperative to note that this inference necessitates further validation through comprehensive and systematic studies. We found the mean OR time was slightly longer in the non-ISBF group than in the ISBF group, although there was no significant difference between the two groups (P>0,05), however, it was still different from what we expected. Our study results prompt consideration of several factors. Firstly, despite our concerted efforts to minimize it, the learning curve inevitably influenced our findings, which is also a common limitation of retrospective studies. Furthermore, this outcome may imply that the additional procedure of acquiring and relocating the bone flap during surgery for patients in the ISBF group does not substantially extend the duration of the operation as the surgeon's proficiency advances. Nonetheless, the ISBF repositioning technique is not without its constraints. Primarily, our clinical observations have indicated that this method is not universally applicable to all patients with IPA, and its implementation is contingent upon several criteria:1. The patient’s sphenoidal sinus must exhibit adequate pneumatization to ensure safe access to the bone flap.2. The bone flap must be devoid of adenoma invasion to circumvent the risk of tumor recurrence due to flap repositioning. These criteria have also been reported by previous scholars (6). In addition, this technique cannot be applied to patients with previous EEA surgery due to the absence of sellar floor bone. It is crucial to acknowledge that these limitations may introduce a potential bias, resulting in the ISBF group appearing to have less aggressive tumor invasiveness compared to the non-ISBF group. Upon reviewing the existing literature, it was determined that several risk factors contribute to CSF leakage following EEA surgery. These factors encompass BMI, tumor size, incidence of intraoperative CSF leakage, perioperative radiotherapy, and diabetes mellitus, etc. Notably, BMI emerged as the primary risk factor, with a higher BMI correlating with an increased likelihood of postoperative CSF leakage (33, 34). We conducted a comprehensive collection and analysis of patient data pertaining to risk factors. Our analysis revealed no significant disparity between the two groups in terms of these risk factors (P>0.05) (Table1), thereby mitigating any bias these factors could potentially introduce to the study’s result. Our study has all shortcomings associated with retrospective studies. Further multi-institutional prospective studies are needed to confirm the utility of ISBF repositioning in IPA patients undergoing EEA surgery. Abbreviations ISBF (In Situ Bone Flap) IPA (Invasive Pituitary Adenoma) EEA (Endoscopic Endonasal Approach) PA (Pituitary Adenoma) CSF (Cerebrospinal Fluid) ON (Optic Nerve) ICA (Internal Carotid Artery) CS (Cavernous Sinus) TV (Third Ventricle) CT (Computed Tomography) BMI (Body Mass Index) OR (Operation) MRI (Magnetic resonance imaging) GTR (gross total resection) CS (Cavernous sinus) Declarations Human Ethics and Consent to Participate declarations: All procedures conducted in our studies adhered to the ethical guidelines set forth by the Institutional Review Board of the First Affiliated Hospital of Nanjing Medical University, in compliance with the principles outlined in the 1964 Helsinki Declaration and its subsequent amendments. An informed consent form was signed by each participant. Consent for publication: not applicable Availability of data and materials: Data is provided within the manuscript or supplementary information files. Funding declaration: This research is financially supported by these following grants: Outstanding Young and Middle-aged Talents Support Program of the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital) Jiangsu Province Capability Improvement Project through Science, Technology and Education, ZDXK202225 Competing interests: The authors declare no conflicts of interest. Authors’ contributions: All authors made significant contributions to this retrospective study. PZ and DW conceptualized the study and designed its framework. PZ, DW, JL, and HC performed surgical procedures on the patients. KC, KY, and ZL were responsible for data collection, statistical analysis, and data interpretation. Additionally, they contributed to the preparation of figures and tables. KC, JL, KY, ZL, KD, and KX drafted the manuscript. HC, ZL, and KC corrected grammatical errors and refined the language of the manuscript. 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BMC surgery. 2021;21(1):103. Zhou Y, Hei Y, Soto JM, Jin T, Jiang X, Feng D, et al. Clinical Efficacy of the Multilayered Skull Base Reconstruction Using In Situ Bone Flap in Endoscopic Endonasal Approach for Craniopharyngioma. Journal of neurological surgery Part B, Skull base. 2022;83(Suppl 2):e291-e7. Gruss CL, Al Komser M, Aghi MK, Pletcher SD, Goldberg AN, McDermott M, et al. Risk factors for cerebrospinal leak after endoscopic skull base reconstruction with nasoseptal flap. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2014;151(3):516-21. Kim JS, Hong SD. Risk factors for postoperative CSF leakage after endonasal endoscopic skull base surgery: a meta-analysis and systematic review. Rhinology. 2021;59(1):10-20. Additional Declarations No competing interests reported. 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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-4334254","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":300513722,"identity":"44774dac-52cf-4cbb-ae62-e3b12bd1ce2a","order_by":0,"name":"Jinlai Liu","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jinlai","middleName":"","lastName":"Liu","suffix":""},{"id":300513723,"identity":"57f79c39-516d-4ba6-98e7-d4a8a450144a","order_by":1,"name":"Kaile Chen","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kaile","middleName":"","lastName":"Chen","suffix":""},{"id":300513725,"identity":"73cfae5d-4682-4465-9464-84d786edc2ce","order_by":2,"name":"Kuo Yu","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kuo","middleName":"","lastName":"Yu","suffix":""},{"id":300513727,"identity":"d5221a6b-cef2-4656-aa7c-7dda8a44f644","order_by":3,"name":"Zhiyuan Liu","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhiyuan","middleName":"","lastName":"Liu","suffix":""},{"id":300513729,"identity":"d46eac57-a736-4f4c-94ec-af6fc33a3d04","order_by":4,"name":"Kexiang Dai","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kexiang","middleName":"","lastName":"Dai","suffix":""},{"id":300513730,"identity":"ec5b371c-44c8-4e8d-aec5-f2e16e19353c","order_by":5,"name":"Ke Xu","email":"","orcid":"","institution":"Department of Neurosurgery, Emergency General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ke","middleName":"","lastName":"Xu","suffix":""},{"id":300513731,"identity":"a1d8b14b-ac06-489a-a07e-ca48e5b94f8b","order_by":6,"name":"Honglu Chao","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Honglu","middleName":"","lastName":"Chao","suffix":""},{"id":300513732,"identity":"3695c137-8e17-4904-9cfd-df7d42eb015c","order_by":7,"name":"Ailin Lu","email":"","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ailin","middleName":"","lastName":"Lu","suffix":""},{"id":300513733,"identity":"c97144da-2e1d-4dd1-824b-b27a29bae5df","order_by":8,"name":"Duqian Wang","email":"","orcid":"","institution":"Department of Neurosurgery, People’s Hosptial of Yangzhong City","correspondingAuthor":false,"prefix":"","firstName":"Duqian","middleName":"","lastName":"Wang","suffix":""},{"id":300513734,"identity":"f3763656-4802-4e5d-809f-edcbbdefd13d","order_by":9,"name":"Peng Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYDACCSjNz8CQAKIZG4jWItlAshaDAxCasBb52c0PHxdU3LHbfLvh6WYeBhvZDQeYnz3Ap4VxzjFj4xlnniVvu3Mg7TYPQ5rxhgNs5gb4tDBLJJhJ87YdTja7kQDScjhxwwEeNgl8Wtgk0r9J8/47nGw8A6zlP2EtPBI5QFsaDtsZSIC1HCCsRUIip9h4xrHDCRJAh92cY5BsPPMwmxleLfIz0jc+Lqg5bM8/IyftxpsKO9m+483P8GoBAWYgTmxg4EkAxg6US4wWewYG9gNEqB0Fo2AUjIKRCADfVUrCtq1jMwAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Peng","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2024-04-27 13:29:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4334254/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4334254/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56543269,"identity":"e306ad65-cd74-46b5-bf61-ab350609b3c8","added_by":"auto","created_at":"2024-05-15 14:36:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":905850,"visible":true,"origin":"","legend":"\u003cp\u003eA: the ISBF was meticulously harvested from the posterior wall of sphenoidal sinus using a high-speed microdrill, following the trajectory indicated by the dotted line in the figure. B: The ISBF was temporarily removed via the nasal cavity, poised for its crucial role in skull base reconstruction. C: The dura was exposed after the removal of ISBF. Fig1D: The dura was incised to reveal the pituitary adenoma, after which resection of the tumor was performed.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4334254/v1/7f7ccc8b434a7edce1bf7276.jpg"},{"id":56543272,"identity":"3db43e99-5f82-48ee-aa03-0da2f3073661","added_by":"auto","created_at":"2024-05-15 14:36:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25592350,"visible":true,"origin":"","legend":"\u003cp\u003eA: The first layer consisted of adipose tissue harvested from the patient’s thigh, which was then filled into the tumor cavity as an inlay graft to eliminate dead space and protect ICAs. B: The second layer involved repositioning the ISBF as an onlay graft, with the use of bioglue to enhance its structural integrity. C: The third layer comprised fascia lata, which covered the ISBF as an additional onlay graft. D: Finally, a synthetic dura was employed to cover the fascia lata, serving as the outermost layer.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4334254/v1/010b82a10fcdc3be6a97f005.jpg"},{"id":56543271,"identity":"24b61b62-c8e7-407b-92d5-82f56d57b2e7","added_by":"auto","created_at":"2024-05-15 14:36:19","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1887662,"visible":true,"origin":"","legend":"\u003cp\u003eA\u0026amp;B: The preoperative MRI pictures of a patient with IPA were presented. 3C\u0026amp;D: The postoperative MRI pictures of the same patient were presented. In both figures, the patient’s skull base formed a rigid reconstructed structure of equal density to the skull bone. Besides, there was no significant sellar floor subsidence and meningoceles shown in the figure.\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4334254/v1/c8f03d98373b5487ae0066ef.jpg"},{"id":74673665,"identity":"1ca91a86-5f9f-4b6f-9c67-8b04c7292b35","added_by":"auto","created_at":"2025-01-24 14:32:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":29188687,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4334254/v1/73275795-2a88-4429-8ffa-32193dd2070f.pdf"},{"id":56543270,"identity":"da0094b0-3b95-4544-b418-f382c8eb450e","added_by":"auto","created_at":"2024-05-15 14:36:19","extension":"xlsx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":18942,"visible":true,"origin":"","legend":"","description":"","filename":"rawdatatg.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4334254/v1/82acf436349689955256652f.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Utilizing In-Situ Bone Flap for Skull Base Reconstruction in Endoscopic Surgery of Invasive Pituitary Adenoma: A Novel Approach","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePituitary adenomas(PAs), ranking as the third most prevalent neurological tumors following gliomas and meningiomas, represent the predominant lesion within the sellar region.(1)\u0026nbsp;Approximately 25% to 55% of pituitary adenomas manifest as invasive pituitary adenomas (IPAs; classified as Knosp III and IV). These IPAs are characterized by their invasion into adjacent tissues. Consequently, they are associated with a less favorable prognosis compared to their non-invasive counterparts.(2)\u003c/p\u003e\n\u003cp\u003eThe Endoscopic Endonasal Approach (EEA) has emerged as the preferred surgical method for pituitary adenoma due to its advantages such as enhanced visualization, minimization of brain injury and neurovascular retraction, and reduced postoperative hospitalization duration, etc.(3) For EEA surgery, the importance of effective skull base reconstruction and comprehensive lesion resection cannot be overstated.(4)\u0026nbsp;Addressing the skull base defect after surgery has consistently posed significant challenges in EEA surgery for PAs. Given that IPAs are often larger in size and infiltrate adjacent tissues, they result in a more extensive skull base defect during endoscopic surgery. This can subsequently escalate the risk of postoperative complications, including CSF and meningitis.(5) There is a paucity of research specifically investigating efficacious methods for skull base reconstruction in EEA surgery of IPAs. Consequently, the exploration of an effective technique is of paramount importance.\u003c/p\u003e\n\u003cp\u003eISBF, characterized by the creation of a bone flap that can be subsequently repositioned and secured within its original location to repair a bony defect resulting from surgical procedures during EEA, has been proved effective in reducing the incidence of postoperative cerebrospinal fluid (CSF) leakage by several scholars.(6)\u0026nbsp;However, the implication of this skull base reconstruction technique on patients with IPA remains ambiguous and necessitate additional exploration.\u003c/p\u003e\n\u003cp\u003eOur research indicates that the technique of ISBF reconstruction of the skull base is a safe and effective strategy for patients with IPA who have undergone EEA surgery.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e\u003cstrong\u003eData collection and analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively collected data on patients with intraoperative pathological diagnosis of pituitary adenomas who underwent EEA surgery from 2018 to 2023. Among them, patients with preoperative imaging grades Knosp III and IV were included in the study. There are 115 patients met the inclusion criteria. 65 of these patients were categorized in the ISBF group by applying the ISBF repositioning technique during the surgery, and the remaining 50 patients were categorized as the non-ISBF group. Patients\u0026rsquo; characteristics, surgical situation and clinical outcomes were evaluated and reviewed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical technique:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore proceeding with the surgery, the patient underwent a comprehensive series of tests to exclude any contraindications to endoscopic endonasal approach (EEA) surgery. Magnetic Resonance Imaging (MRI) was employed to quantify the tumor size and delineate the extent of tumor invasion into peripheral neurovascular structures, including the optic nerve (ON), internal carotid artery (ICA), and cavernous sinus (CS), third ventricle (TV), among others. This information is crucial for the strategic planning and execution of the surgical procedure. Additionally, Computed Tomography (CT) was utilized to assess bony structure of sellar region and sphenoidal sinus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients were intubated and positioned supine prior to the procedure. The surgical approach employed was the two-nostril/two-surgeon/four-hands technique, necessitating a posterior septectomy to enhance visualization. Throughout the surgery, the endoscope was secured to a pneumatic arm, providing a stable view and increased flexibility for the surgeon. Systematic preparation of the right thigh was undertaken for harvesting adipose tissue and fascia lata. To mitigate mucosal hemorrhage, the nasal cavity was packed with cottonoids soaked in adrenaline for 10 minutes. All patients received prophylactic antibiotics (cefuroxime sodium) 30 minutes before the incision. The anterior wall of sphenoidal sinus was carefully opened wide with microdrill with diamond burr to expose the sphenoidal sinus cavity and then sphenoid septation was removed with a Kerrison rongeur. During the process of accessing the pituitary fossa via the opening of the posterior wall of the sphenoidal sinus, an ISBF was harvested, in accordance with methods previously documented in the literature.(6)\u0026nbsp;The coronal dimensions of the ISBF were typically confined between the bilateral ICA protuberances or between the bilateral optic protuberances. The sagittal dimensions of the bone flap were adjustable, contingent upon the location and size of the lesion. A high-speed micro drill was employed to perform an incision on the skull base bone along the dotted line demarcated in Fig1A, facilitating the extraction of the ISBF. After the incision, the bone flap was meticulously elevated from the dura mater (Fig1B). Throughout this procedure, it was imperative to preserve the integrity of the flap to mitigate the risk of inflicting damage to the adjacent tissues due to potential partial rupture and subsequent displacement of the flap following repositioning. Depending on the surgical requirements, the flap could either be folded to one side or temporarily excised via the nasal cavity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter the resection of the tumor, the skull base reconstruction was performed. Different reconstruction techniques were used for the ISBF group and non-ISBF group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the non-ISBF group, a multilayer reconstruction was systematically employed. The first layer was constituted by adipose tissue, harvested from the patient\u0026rsquo;s thigh, which was then inserted into tumor cavity as an inlay graft. The subsequent layer was composed of the fascia lata, procured from an incision on the patient\u0026rsquo;s thigh, serving as an onlay graft. Finally, the synthetic dura was strategically positioned over the fascia lata graft, forming the third layer.\u003c/p\u003e\n\u003cp\u003eWithin the introduction of the ISBF repositioning technique, we adopted a distinct reconstruction strategy for the selected patients in the ISBF group. The first layer was constituted by adipose tissue obtained from thigh, which was filled into tumor cavity to eliminate the dead space (Fig2A). Subsequently, the harvested ISBF was repositioned to cover the bone defect, forming the second layer, which was different from the approach to skull base reconstruction in patients in the non-ISBF group (Fig2B). The third layer was composed of the fasica lata from thigh, covering the ISBF (Fig2C). Finally, the synthetic dura was applied to cover the fasica lata as the fourth layer (Fig2D).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe surgeries were performed by an experienced surgeon (Prof. Peng Zhao) in the Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, thus minimizing the confounding factors brought by learning curve.\u0026nbsp;(7)\u0026nbsp;The prophylactic lumbar drainage was not routinely performed in the patients, because there is few evidence to support that adjunctive lumbar drainage significantly reduces the incidence of postoperative CSF leak.\u0026nbsp;(8)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePostoperative management:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients underwent CT scan right after the surgery to determine if there was any postoperative intracranial hemorrhage. Following the surgical intervention, all patients underwent an enhanced MRI within a 48-hour period, aiming to ascertain the degree of tumor resection, evaluate the integrity of the skull base reconstruction, and assess potential damage inflicted upon the adjacent vascular and neural structures. All patients were subjected to a diagnostic \u0026lsquo;tilt test\u0026rsquo; to identify the pressure of CSF rhinorrhea. During this test, patients were instructed to incline their head downward for 30 seconds. A persistent watery discharge from one or both nostrils typically signifies a failed repair resulting in CSF rhinorrhea. Conversely, a discharge resembling a thicker mucus-like substance does not indicate CSF rhinorrhea.(9) In addition, we conducted a series of chemical analyses, including the glucose oxidase assay and the \u0026beta;2-transferrin test, on the rhinorrhea samples collected from patients. These tests serve as valuable tools in the diagnostic process for CSF leakage.(10)\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean age of patients in the ISBF and non-ISBF groups was 52.13 and 51.90 years, respectively, with no significant difference observed (P = 0.264). The sex distribution across both groups was also statistically similar, with females constituting 47% (31/65) of the ISBF group and 58% (29/50) of the non-ISBF group (P = 0.273). In the non-ISBF group, two patients had a history of recurrent IPA and had previously been treated with EEA surgery. However, in the ISBF group, there were no cases of recurrent IPA. Statistical analysis revealed no significant difference between them (P = 0.364). The size of tumor, quantified as the maximum diameter derived from preoperative MRI, exhibited no significant disparity between the ISBF group (26.15 mm) and the non-ISBF group (29.67 mm) (P = 0.114). Furthermore, no significant differences were found between the ISBF and non-ISBF group in terms of medical history, including diabetes, hypertension, and coronary heart disease (CHD) (P = 0.686, 0.252, 1.00). The comparison of the Body Mass Index (BMI) between the two groups did not yield any statistically significant differences (P = 0.872). Lastly, the Knosp grade of each patient\u0026rsquo;s tumor was ascertained through preoperative enhanced MRI. Upon statistical analysis, the distribution of Knosp grades between the two groups did not demonstrate any significant disparity (P = 0.880). (Table1)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical situation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntraoperative CSF leakage was observed in 7 patients from the ISBF group and 8 patients from the non-ISBF group, yielding no statistically significant differences (P = 0.409). Notably, the mean operation time (OR time) for ISBF patients was 86 minutes, while the non-ISBF patients with a mean OR time of 98 minutes, with no significant disparity between the two groups (P = 0.144). (Table2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical outcomes:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWithin the ISBF cohort, a singular instance of postoperative CSF leakage was observed (1/65, 1.53%), in contrast to the non-ISBF cohort where 8 instances were reported (8/50, 16%). This disparity in the incidence of CSF leakage between the two cohorts is statistically significant(P=0.012). The average length of postoperative hospitalization for patients within the ISBF group was 5.50 days, comparatively less than the 7.10 days noted in the non-ISBF group, despite this, the difference did not reach statistical significance (P=0.081). Postoperative polyuria was observed in 6 patients in the ISBF group (6 out of 65, 9.23%) and in 5 patients in the non-ISBF group (5 out of 50, 10%), with no significant differences noted. Two patients in the ISBF group developed postoperative meningitis (2 out of 65, 3.07%), compared to four patients in the non-ISBF group (4 out of 50, 8%). However, there was no statistical difference between the two groups (P=0.451). Lastly, none of the patients in either group experienced postoperative ON injury or ICA injury associated with ISBF harvesting and repositioning. (Table 3)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable1 patient characteristics\u003c/strong\u003e:\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"583\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eISBF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-ISBF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo of patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.273\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e52.13\u0026plusmn;14.199(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e51.90\u0026plusmn;12.98(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.246\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor size\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e26.15\u0026plusmn;9.40(mm)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e29.67\u0026plusmn;11.90(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e24.92\u0026plusmn;4.69(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e25.77\u0026plusmn;3.68(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.686\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrevious surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadiotherapy history\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eKnosp grade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.880\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable2 surgical situation:\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"583\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.101200686106345%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.214408233276156%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eISBF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-ISBF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.101200686106345%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraoperative CSF leak\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.214408233276156%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e0.409\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.101200686106345%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.214408233276156%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.101200686106345%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOperation time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.214408233276156%\" valign=\"top\"\u003e\n \u003cp\u003e86.35\u0026plusmn;33.79(min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e98.92\u0026plusmn;24.64(min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.842195540308747%\" valign=\"top\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable3 clinical outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"579\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eISBF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-ISBF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative CSF leakage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative epistaxis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative polyuria\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative meningitis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative hospital stays\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.50\u0026plusmn;1.23(days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7.10\u0026plusmn;1.84(days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eICA injury\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e`0\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.689655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eON injury\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.310344827586206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe repositioning of ISBF presents a dependable, expedient, and viable technique for skull base reconstruction in patients with IPA undergoing EEA surgery. Our preliminary study results indicate that the ISBF, when combined with a multilayer closure technique, significantly reduces the incidence of postoperative CSF leakage without increasing the occurrence of other complications.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePituitary adenomas, benign in nature, account for a significant proportion, specifically 10% to 15%, of intracranial neoplasms. Despite their benign classification, a subset of these adenomas exhibits aggressive clinical behaviors, including rapid proliferation, invasion of surrounding tissues and resistance to conventional treatment.(11)\u0026nbsp;The treatment of IPAs presents significant challenges due to their propensity to invade adjacent structures, including the cavernous sinus, dura, ICAs, ONs, TV, etc. The Knosp grade system was proposed in 1993 to classify pituitary adenoma according to the tumor anatomical relationship between ICAs. Within this system, grades III, IV are designated as IPAs.\u0026nbsp;(12)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEEA surgery has become the first-line treatment for IPAs due to its advantages over microscopic surgery such as higher gross total resection (GTR) rate, more flexible maneuvering, better visualization, and better postoperative improvement of endocrine function, etc.\u0026nbsp;(13, 14)\u0026nbsp;Because IPAs invaded surrounding tissues, especially CS, the extended EEA approach was required to obtain better exposure and increase tumor resection rate.\u0026nbsp;(15, 16)\u0026nbsp;Previous studies noted that GTR of approximately 80% could be achieved utilizing extended EEA approach to remove IPAs, and high GTR rate tends to result in a better prognosis.\u0026nbsp;(17, 18)\u0026nbsp;The intraoperative assistance of Doppler ultrasound and magnetic neuronavigational system was essential to prevent damage to peripheral neurovascular structures during extended EEA surgery, especially the ICAs.\u0026nbsp;(19, 20)\u0026nbsp;Many scholars kept pushing the boundaries of indications for extended EEA approach. Certain distinct subtypes of pituitary adenomas such as dumbbell-shape tumors, pure suprasellar adenomas, fibrous adenomas, have historically proven refractory to conventional EEA surgery. However, these challenging cases can now be effectively addressed through the extended EEA approach.\u0026nbsp;(21)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe successful execution of EEA surgery for IPAs hinges on two critical factors: the comprehensive resection of the tumor and effective skull base reconstruction.(4)\u0026nbsp;Patients who have undergone EEA surgery are susceptible to postoperative complications associated with skull base defects, including CSF leak and meningitis, which may prolong hospitalization and lead to repeated surgery.\u0026nbsp;(22)Patients with IPA are more susceptible to postoperative CSF leaks compared to patients with non-IPA. This increased risk is attributed to the larger tumor volume and the skull base defects that occur during surgery.\u0026nbsp;(23, 24)\u0026nbsp;Consequently, it is imperative to investigate more effective strategies for skull base reconstruction in EEA surgery for IPAs. The multilayer construction technique, which employs a combination of autologous and synthetic materials, is a prevalent practice in clinical settings. This method encompasses the use of free autografts, intranasal vascularized flaps, synthetic dural replacement grafts, and pedicled nasoseptal flaps.\u0026nbsp;(4, 25)\u0026nbsp;However, it is important to note that these materials are not fully capable of repairing bony defects of the skull base.\u003c/p\u003e\n\u003cp\u003eIt has previously been suggested that rigid reconstruction of the skull base was unnecessary by some literature.\u0026nbsp;(26)\u0026nbsp;However, in recent years, an increasing number of scholars now advocate for a more affirmative stance regarding rigid reconstruction. Their rationale centers on the potential effectiveness of these procedures in mitigating complications associated with skull base defects, including acute or chronic headaches and pseudo meningoceles.\u0026nbsp;(6)\u0026nbsp;Various rigid reconstruction material has been explored and proposed recently, including bioabsorbable plate, hydroxyapatite cement, titanium mesh, autologous cartilage, etc.\u0026nbsp;(27-30)\u0026nbsp;Compared to these materials, ISBF has better histocompatibility, conforms better to the complex anatomy of the skull base, and has lower risk of infection and damage to adjacent tissues due to graft displacement.\u0026nbsp;(31)\u0026nbsp;Previous studies have demonstrated the effectiveness of applying ISBF for skull base reconstruction in EEA surgery.\u0026nbsp;(31, 32)\u0026nbsp;However, there are no studies exploring the role of ISBF in skull base reconstruction in EEA surgery for IPAs.\u0026nbsp;Our investigation revealed\u0026nbsp;that the ISBF technique was also effective in reducing the incidence of postoperative CSF leak in IPA patients.\u003c/p\u003e\n\u003cp\u003eThroughout the course of our investigation, we observed that patients within the ISBF group exhibited minimal sellar floor subsidence, as evidenced by postoperative MRI. We postulated that a reduced degree of sellar floor subsidence could potentially mitigate the extent of pituitary stalk traction, thereby diminishing the incidence of postoperative polyuria. This hypothesis appears to align with the lower incidence of postoperative polyuria observed in ISBF group patients (10.16%) compared to those in non-ISBF group (11.11%), despite the lack of statistical significance (P\u0026gt;0.05). However, it is imperative to note that this inference necessitates further validation through comprehensive and systematic studies.\u003c/p\u003e\n\u003cp\u003eWe found the mean OR time was slightly longer in the non-ISBF group than in the ISBF group, although there was no significant difference between the two groups (P\u0026gt;0,05), however, it was still different from what we expected. Our study results prompt consideration of several factors. Firstly, despite our concerted efforts to minimize it, the learning curve inevitably influenced our findings, which is also a common limitation of retrospective studies. Furthermore, this outcome may imply that the additional procedure of acquiring and relocating the bone flap during surgery for patients in the ISBF group does not substantially extend the duration of the operation as the surgeon\u0026apos;s proficiency advances.\u003c/p\u003e\n\u003cp\u003eNonetheless, the ISBF repositioning technique is not without its constraints. Primarily, our clinical observations have indicated that this method is not universally applicable to all patients with IPA, and its implementation is contingent upon several criteria:1. The patient\u0026rsquo;s sphenoidal sinus must exhibit adequate pneumatization to ensure safe access to the bone flap.2. The bone flap must be devoid of adenoma invasion to circumvent the risk of tumor recurrence due to flap repositioning. These criteria have also been reported by previous scholars (6). In addition, this technique cannot be applied to patients with previous EEA surgery due to the absence of sellar floor bone. It is crucial to acknowledge that these limitations may introduce a potential bias, resulting in the ISBF group appearing to have less aggressive tumor invasiveness compared to the non-ISBF group.\u003c/p\u003e\n\u003cp\u003eUpon reviewing the existing literature, it was determined that several risk factors contribute to CSF leakage following EEA surgery. These factors encompass BMI, tumor size, incidence of intraoperative CSF leakage, perioperative radiotherapy, and diabetes mellitus, etc. Notably, BMI emerged as the primary risk factor, with a higher BMI correlating with an increased likelihood of postoperative CSF leakage\u0026nbsp;(33, 34). We conducted a comprehensive collection and analysis of patient data pertaining to risk factors. Our analysis revealed no significant disparity between the two groups in terms of these risk factors (P\u0026gt;0.05) (Table1), thereby mitigating any bias these factors could potentially introduce to the study\u0026rsquo;s result.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study has all shortcomings associated with retrospective studies. Further multi-institutional prospective studies are needed to confirm the utility of ISBF repositioning in IPA patients undergoing EEA surgery.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eISBF (In Situ Bone Flap)\u003c/p\u003e\n\u003cp\u003eIPA (Invasive Pituitary Adenoma)\u003c/p\u003e\n\u003cp\u003eEEA (Endoscopic Endonasal Approach)\u003c/p\u003e\n\u003cp\u003ePA (Pituitary Adenoma)\u003c/p\u003e\n\u003cp\u003eCSF (Cerebrospinal Fluid)\u003c/p\u003e\n\u003cp\u003eON (Optic Nerve)\u003c/p\u003e\n\u003cp\u003eICA (Internal Carotid Artery)\u003c/p\u003e\n\u003cp\u003eCS (Cavernous Sinus)\u003c/p\u003e\n\u003cp\u003eTV (Third Ventricle)\u003c/p\u003e\n\u003cp\u003eCT (Computed Tomography)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI (Body Mass Index)\u003c/p\u003e\n\u003cp\u003eOR (Operation)\u003c/p\u003e\n\u003cp\u003eMRI (Magnetic resonance imaging)\u003c/p\u003e\n\u003cp\u003eGTR (gross total resection)\u003c/p\u003e\n\u003cp\u003eCS (Cavernous sinus)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures conducted in our studies adhered to the ethical guidelines set forth by the Institutional Review Board of the First Affiliated Hospital of Nanjing Medical University, in compliance with the principles outlined in the 1964 Helsinki Declaration and its subsequent amendments.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn informed consent form was signed by each participant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is provided within the manuscript or supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research is financially supported by these following grants:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eOutstanding Young and Middle-aged Talents Support Program of the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital)\u003c/li\u003e\n \u003cli\u003eJiangsu Province Capability Improvement Project through Science, Technology and Education, ZDXK202225\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors made significant contributions to this retrospective study. PZ and DW conceptualized the study and designed its framework. PZ, DW, JL, and HC performed surgical procedures on the patients. KC, KY, and ZL were responsible for data collection, statistical analysis, and data interpretation. Additionally, they contributed to the preparation of figures and tables. KC, JL, KY, ZL, KD, and KX drafted the manuscript. HC, ZL, and KC corrected grammatical errors and refined the language of the manuscript. PZ, DW, and AL critically reviewed the initial draft and contributed to its finalization. Finally, all authors participated in reviewing the final version of the manuscript and consented to its submission for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAldahmani KM, Sreedharan J, Ismail MM, Philip J, Nair SC, Alfelasi M, et al. 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Extended endoscopic endonasal approach for selected pituitary adenomas: early experience. Journal of neurosurgery. 2011;114(2):345-53.\u003c/li\u003e\n\u003cli\u003eWerner MT, Yeoh D, Fastenberg JH, Chaskes MB, Pollack AZ, Boockvar JA, et al. Reconstruction of the Anterior Skull Base Using the Nasoseptal Flap: A Review. Cancers. 2023;16(1).\u003c/li\u003e\n\u003cli\u003eMunich SA, Fenstermaker RA, Fabiano AJ, Rigual NR. Cranial base repair with combined vascularized nasal septal flap and autologous tissue graft following expanded endonasal endoscopic neurosurgery. Journal of neurological surgery Part A, Central European neurosurgery. 2013;74(2):101-8.\u003c/li\u003e\n\u003cli\u003eCavallo LM, Messina A, Esposito F, de Divitiis O, Dal Fabbro M, de Divitiis E, et al. Skull base reconstruction in the extended endoscopic transsphenoidal approach for suprasellar lesions. Journal of neurosurgery. 2007;107(4):713-20.\u003c/li\u003e\n\u003cli\u003eXing M, Lv W, Liu P, Wang J, Gao W, Xu Y, et al. Multi-layer reconstruction of skull base after endoscopic transnasal surgery for invasive pituitary adenomas. Neurologia i neurochirurgia polska. 2023;57(2):160-8.\u003c/li\u003e\n\u003cli\u003eEloy JA, Shukla PA, Choudhry OJ, Singh R, Liu JK. Assessment of frontal lobe sagging after endoscopic endonasal transcribriform resection of anterior skull base tumors: is rigid structural reconstruction of the cranial base defect necessary? The Laryngoscope. 2012;122(12):2652-7.\u003c/li\u003e\n\u003cli\u003eLee SH, Ha CM, Hong SD, Choi JW, Seol HJ, Nam DH, et al. Clinical Impact of Hydroxyapatite on the Outcome of Skull Base Reconstruction for Intraoperative High-Flow CSF Leak: A Propensity Score Matching Analysis. Frontiers in oncology. 2022;12:906162.\u003c/li\u003e\n\u003cli\u003eFermi M, Serafini E, Rosti A, Olive M, Alicandri-Ciufelli M, Sciarretta V, et al. Multilayer Anterior Skull Base Reconstruction with Cortical Rib Bone Graft: Preliminary Experience. World Neurosurg. 2023;179:e110-e8.\u003c/li\u003e\n\u003cli\u003eAl-Asousi F, Okpaleke C, Dadgostar A, Javer A. The use of polydioxanone plates for endoscopic skull base repair. American journal of rhinology \u0026amp; allergy. 2017;31(2):122-6.\u003c/li\u003e\n\u003cli\u003eSeaman SC, Moline MJ, Graham SM, Greenlee JDW. Endoscopic extrasellar skull base reconstruction using bioabsorbable plates. American journal of otolaryngology. 2021;42(1):102750.\u003c/li\u003e\n\u003cli\u003eZhou ZY, Wang XS, Gong Y, La Ali Musyafar O, Yu JJ, Huo G, et al. Treatment with endoscopic transnasal resection of hypothalamic pilocytic astrocytomas: a single-center experience. BMC surgery. 2021;21(1):103.\u003c/li\u003e\n\u003cli\u003eZhou Y, Hei Y, Soto JM, Jin T, Jiang X, Feng D, et al. Clinical Efficacy of the Multilayered Skull Base Reconstruction Using In Situ Bone Flap in Endoscopic Endonasal Approach for Craniopharyngioma. Journal of neurological surgery Part B, Skull base. 2022;83(Suppl 2):e291-e7.\u003c/li\u003e\n\u003cli\u003eGruss CL, Al Komser M, Aghi MK, Pletcher SD, Goldberg AN, McDermott M, et al. Risk factors for cerebrospinal leak after endoscopic skull base reconstruction with nasoseptal flap. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2014;151(3):516-21.\u003c/li\u003e\n\u003cli\u003eKim JS, Hong SD. Risk factors for postoperative CSF leakage after endonasal endoscopic skull base surgery: a meta-analysis and systematic review. Rhinology. 2021;59(1):10-20.\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":"invasive, aggressive, skull base reconstruction, pituitary adenoma, endoscopic, transsphenoidal, CSF leakage, in-situ bone flap, rigid ","lastPublishedDoi":"10.21203/rs.3.rs-4334254/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4334254/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To\u003cstrong\u003e \u003c/strong\u003eevaluate the efficacy of in-situ bone flap (ISBF) repositioning technique in skull base reconstruction for invasive pituitary adenoma (IPA) via endoscopic endonasal approach (EEA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e In a retrospective study spanning the years 2018 to 2023, we investigated the efficacy of in-situ bone flap (ISBF) repositioning technique in patients with invasive pituitary adenoma (IPA) who underwent endoscopic endonasal surgery (EEA). Among the 115 patients included in the study, 65 were assigned to the group, while the remaining 55 were categorized into the non-ISBF group. Comprehensive data on patients’ basic characteristics, surgical situation, and clinical outcomes were meticulously collected and analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In our study, we observed postoperative cerebrospinal fluid (CSF) leakage in 1 out of 65 patients in the ISBF group, while 8 out of 50 patients in the non-ISBF group experienced this complication, indicating a significant difference (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe ISBF repositioning technique emerges as an effective and feasible method for skull base reconstruction in patients who have underwent EEA surgery for IPA. Notably, this technique significantly reduces the incidence of postoperative CSF leakage.\u003c/p\u003e","manuscriptTitle":"Utilizing In-Situ Bone Flap for Skull Base Reconstruction in Endoscopic Surgery of Invasive Pituitary Adenoma: A Novel Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-15 14:36:14","doi":"10.21203/rs.3.rs-4334254/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":"bc7ffd76-4391-4095-b6e0-bd712cc5ae1b","owner":[],"postedDate":"May 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-24T14:24:03+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-15 14:36:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4334254","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4334254","identity":"rs-4334254","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}