Endoscopic endonasal resection of giant pituitary neuroendocrine tumors - case series from the referral pituitary center

Endoscopic endonasal resection of giant pituitary neuroendocrine tumors - case series from the referral pituitary center | 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 Endoscopic endonasal resection of giant pituitary neuroendocrine tumors - case series from the referral pituitary center Jacek Kunicki, Barbara Buchalska, Maria Maksymowicz, Szymon Baluszek, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7557934/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Nov, 2025 Read the published version in Pituitary → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose The giant pituitary adenomas (GPAs) are still a challenging surgical problem. They comprise 10–15% of operated pituitary adenomas. The advances of endoscopic techniques allow the resection of pituitary tumors previously operated by transcranial approaches. The aim of the study was to review the surgical results in a series of patients with GPAs (diameter ≥ 40 mm) operated with endoscopic endonasal approach. Methods The study is a retrospective analysis of a series of 176 patients (66 women and 110 men) treated from the 2007 to 2023 by the endoscopic transsphenoidal surgeries for GPAs (> 40mm). The mean age of the patients was 57.0 years (20–81 years), and the mean follow-up period was 7.5 years (0–16 years). Forty patients had 1a grade of the Lyon’s clinicopathologic classification, 7 patients – 1b, 111 patients – 2a, and 18 patients – 2b. Results The gross total resection was accomplished in 73 cases (41.5%). Extended endoscopic approaches were used in 11 patients (6.3%). The mortality rate was 2.3%. Postoperatively 60% of the patients showed varying improvement in visual field defects and visual acuity. The morbidity rate was 33.5%. During a mean 7.5 years follow-up there were 29 (15.9%) cases of recurrences. Conclusion Our results indicate that resection with endoscopic endonasal approach can be a safe and effective method for the treatment of patients with GPAs. It is the alternative for transcranial approaches. giant pituitary adenomas endoscopic endonasal approach Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Pituitary neuroendocrine tumors (PitNETs), previously known as pituitary adenomas, comprise 10–15% of all brain tumors, and are the most common neuroendocrine tumors of the central nervous system [ 1 ]. There are different definitions of giant pituitary adenomas (GPAs) using morphological tumor parameters e.g. linear diameters, volumetric assessment, and anatomical extent [ 2 – 6 ]. Practically, the most commonly used definition is one that describes a tumor with a maximum diameter of 40 mm or more [ 7 – 10 ]. GPAs account for approximately 10% of surgically treated pituitary tumors [ 11 ]. Due to their large volume and high rates of extrasellar invasion, surgical treatment remains challenging [ 12 ]. Complete resection of GPAs is often not achieved, and they tend to recur more frequently than other PitNETs [ 12 ]. Treatment of GPAs is more frequently associated with serious complications [ 12 ]. Traditionally, transcranial and transsphenoidal microscopic surgical approaches have played a central role in the management of GPAs [ 13 ]. However, in the past two decades, endoscopic endonasal transsphenoidal surgery (EETS) has been increasingly used [9; 13; 14]. The use of EETS for GPA treatment is associated with improved outcomes, including a greater extent of resection and lower morbidity [ 13 ]. This study aimed to review the surgical outcomes in a series of patients with GPAs operated using the endoscopic endonasal approach in the referral pituitary center. Materials and Methods Study population We retrospectively analyzed 176 patients with GPAs who underwent transsphenoidal endoscopic surgery at The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between 2007 and 2023. During this period 2323 patients with pituitary adenomas were treated surgically at our center, with GPAs comprising 7.6% of cases(n = 176/2323). GPAs also accounted for 14.0% of all macroadenomas operated at our center (n = 176/1261). All procedures were performed by the same dedicated neurosurgical team. Inclusion criteria included age ≥ 18 years, histologically confirmed diagnosis of PitNET, maximum tumor diameter ≥ 40 mm, and surgical treatment using the EETS technique. Data collection Clinical and demographic data were obtained from patient medical records, including age, sex, clinical presentation, hospital stay duration, and follow-up period. Tumor characteristics included maximum dimensions (in mm), consistency, invasive features, and pathological results. Classification was based on the 2022 WHO classification of pituitary tumors [ 15 ] and the Lyon’s clinicopathological classification [ 16 ]. Surgical data included the extent of tumor resection—gross total resection (GTR), near-total resection (NTR, ≥ 95%), subtotal resection (STR, ≥ 80%), and partial resection (PR, < 80%)—as well as the method of sellar reconstruction. Additional data were collected on postoperative complications, reoperations, and hospital readmissions. The permanent arginine vasopressin deficiency (diabetes insipidus, DI) was defined as DI persisting for ≥ 6 months. All patients underwent comprehensive pre- and postoperative evaluations, including visual field testing, neurological examination (with emphasis on cranial nerve assessment), and hormonal blood analysis. Preoperatively, each patient received a pituitary magnetic resonance imaging (MRI) scan to confirm tumor localization, visual field testing, a neurological examination, and assessment of anterior pituitary hormone levels, including growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Postoperative assessment included a head computed tomography (CT) scan within 24 hours of surgery to evaluate the extent of resection and exclude intracranial hemorrhagic complications, and a repeat hormonal analysis. Patients with postoperative complications underwent additional CT scans as needed. Follow-up imaging included a pituitary MRI within 2 to 3 months after surgery, repeated every year for 3 years, then repeated every 2 years, and additionally as clinically indicated to monitor for tumor progression. Tumor size and Knosp grade were assessed radiologically. Progression was defined as an increase in tumor volume of ≥ 20%. Follow-up data were obtained through outpatient clinic records and structured telephone interviews, with a response rate of 71.6% (126 of 176 patients). Patient vital status was verified via a government-maintained death registry. To evaluate the influence of accumulated experience, we divided the study period (2007–2023) into four consecutive intervals – the first spanning 5 years, followed by three subsequent 4-year intervals. This subdivision enabled longitudinal assessment of surgical outcomes and complication rates over time. Tumor samples collected intraoperatively were fixed in 10% buffered formalin, embedded in paraffin, and stained with hematoxylin and eosin (H&E). Immunohistochemistry (IHC) was performed using primary antibodies against anterior pituitary hormones: GH, PRL, ACTH, TSH, FSH, LH, and α-SU (alpha-subunit). In cases requiring more detailed analysis, IHC was performed for the pituitary transcription factors: PIT-1, TPIT, and SF-1. Antibodies were sourced from Thermo Scientific, Dako, NeoMarkers, Novocastraor BIO-RAD companies. Staining procedures were made on paraffin sections using the EnVision TM FlexVisualization System with DAB (3,3’ – diaminobenzidine) as chromogen (K8000, Dako/Agilent). Ki-67 proliferation index was evaluated using Dako antibodies. Electron microscopy (EM) was performed in 168 patients. Tissue samples were fixed in 2.5% glutaraldehyde and postfixed in 1% osmium tetroxide, dehydrated in ethanol and propylene oxide, then embedded in epoxy resin (Epon 812). Ultrathin sections were counterstained with uranyl acetate and lead citrate and analyzed using a Philips CM120 BioTWIN transmission electron microscope. Surgical Approach All surgeries were performed using the EETS technique by the same neurosurgeon experienced in pituitary surgery. A standard endoscopic approach was used in the majority of cases, either via a one-and-a-half nostril approach (n = 54/176; 30.7%), or a binostril approach (n = 122/176; 69.3%). In 11 patients (6.3%), an extended transtubercular or transplanar approach was used to address selected suprasellar tumor extensions. Data analysis Descriptive statistics, including mean, median, standard deviation, minimum, and maximum values, were calculated. Fisher’s exact tests and survival analyses were performed using GraphPad software. R (v4.2.2) was utilized for univariate and multivariate analyses. Statistical inference was performed with generalized linear model (glm) and Cox proportional hazards model (coxph). In multivariate analysis L1 regularization with glmnet was implemented to control for the number of input features. A significance level of p < 0.05 was assumed for all analyses. Results General characteristics Most patients were men (n = 110; 62.5%), and the mean age of the patients was 57.0 +-13.2 years (Table 1 ). The mean follow-up duration was 7.5 years ranging from 0 to 16 years. The average postoperative hospital stay was 7.1 days (range: 2–30 days). The most common initial symptoms were were visual disturbances (n = 154; 87.5%), followed by the endocrine disorders (n = 104; 59.1%), neurological deficits (n = 44; 25.0%), headache (n = 19; 10.8%) and symptomatic pituitary apoplexy (n = 18; 10.2%). Endocrine disorders included symptomatic hypopituitarism (n = 86; 48.9%), hyperprolactinemia (n = 51; 29.0%), acromegaly (n = 5; 2.8%), and Cushing’s disease (n = 3; 1.7%). Three patients were asymptomatic, and their GPAs were discovered incidentally during workups for unrelated conditions. At the time of analysis 160 patients were alive (90.9%). Four patients died due to complications (2.3%). The remaining patients had died due to causes unrelated to GPA. Table 1 General characteristics of the patients Variables Value/number of patients Percentage of patients Age - - mean age [years] 57.0 - median age [years] 60 - range [years] 20–81 - Gender - - male 110 62.5% female 66 37.5% Follow-up time - - mean [years] 7.5 - median [years] 7 - range [years] 0–16 - Number of days spent at the hospital after the surgery - - mean 7.1 - median 6 - range 2–30 - Clinical presentation - - visual defects 154 87.5% endocrine defects, including: 104 59.1% hypopituitarism 86 48.9% hyperprolactinemia 51 29.0% acromegaly 5 2.8% Cushing’s disease 3 1.7% other neurological deficits 44 25.0% headache 19 10.8% pituitary apoplexy 18 10.2% non-significant 3 1.7% Knosp scale grade II 90 51.1% III 49 27.8% IV 37 21.0% Maximum tumor diameter - - mean [mm] 46.2 - median [mm] 43.5 - range [mm] 40–90 - Consistency of the tumor - - soft 155 88.1% fibrous 21 11.9% Functional status of the tumor - - functioning 21 11.9% non-functioning 155 88.1% Invasiveness of the tumor - - invasive 130 73.8% cavernous sinus invasion 80 45.5% sphenoid sinus invasion 45 25.6% sellar diaphragm invasion 38 21.6% sella turcica invasion 33 18.8% clivus invasion 22 12.5% invasion to the third ventricle 19 10.8% subarachnoidal space invasion 7 4.0% non-invasive 47 26.7% Tumor characteristics The mean maximal tumor diameter was 46.2 millimeters (range: 40–90 mm) (Table 2 ). Most tumors were non-functioning (n = 155; 88.1%), while 21 cases (11.9%) were hormonally active. Tumor consistency was described as soft in 155 patients (88.1%) and fibrous in 21 patients (11.9%). All tumors had suprasellar extension. Table 2 Surgical characteristics Variables Number of patients Percentage of patients Resection - - GTR and NTR 73 41.5% STR 77 43.7% PR 26 14.8% Surgical endoscopic approach - - Standard 165 93.8% Extended 11 6.3% Reconstruction of sella with a fat tissue graft 110 62.5% Intraoperative CSF leak 95 54.0% Biopsy 3 1.7% Recurrence of the tumor 28 15.9% Residual disease 103 58.5% Reoperation - - Patients without reoperations 141 80.1% Early reoperation due to complications 17 9.7% Due to tumor regrowth 18 10.2% Surgery performed in two parts 4 2.3% Number of patients readmitted to the hospital 29 16.5% Number of readmissions 45 - Mean number of readmissions 1.6 - Knosp grade distribution was as follows: grade II in 90 patients (51.1%), grade III in 49 patients (27.8%), and grade IV in 37 patients (21.0%). There was a statistically significant association between gender and Knosp grade (Fisher’s exact test, p = 0.018). More women had grade III or IV tumors (n = 41/66; 62.1%) compared to men (n = 45/110; 40.9%). Most GPAs were invasive (n = 130; 73.8%). The most common direction of invasion was into the cavernous sinus (n = 80; 45.5%), and the least common was into the subarachnoid space (n = 7; 4.0%) (Table 1 ). There was also a significant association between tumor invasiveness and Knosp grade (Fisher’s exact test, p = 0.0009). All grade IV tumors (n = 37/37) and 75.5% of grade III tumors (n = 37/49) assessed basing on MRI were classified as invasive after an intraoperative evaluation. The most common histopathological diagnosis was gonadotroph adenoma (n = 120; 68.2%), including oncocytic variants (n = 27/120; 22.5%). Nineteen patients initially diagnosed with null cell adenomas (10.8%) basing on standard immunohistochemical stainings were reclassified as gonadotroph adenomas based on ultrastructural and transcription factor analysis (Supplementary Table 1). According to Lyon’s clinicopathological classification, 40 patients (22.7%) had grade 1a tumors, 7 (4.0%) had grade 1b, 111 (63.1%) had grade 2a, and 18 (10.2%) had grade 2b tumors. The proportion of proliferative tumors was similar between invasive (14.9%) and non-invasive (14.0%) cases. Surgical results The extent of resection was subtotal (STR) in 77 patients (43.7%), gross total or near-total (GTR/NTR) in 73 (41.5%), and partial resection (PR) in 26 (14.8%). In 110 cases (62.5%), the sellar floor was reconstructed using fat grafts, either due to intraoperative cerebrospinal fluid (CSF) leaks (n = 90/110; 81.8%) or significant herniation of the diaphragm/suprasellar cisterns (n = 20/110; 18.2%). Five patients had intraoperative CSF leak managed without using sellar floor reconstruction with fat grafts. Knosp grade was significantly associated with extent of resection (Fisher’s exact test, p < 0.0001). GTR/NTR was most common in patients with grade II tumors (n = 49/73; 67.1%), followed by grade III (n = 23/73; 31.5%) and grade IV (n = 1/73; 1.4%) tumors (Supplementary Table 2). STR was predominant among patients with grade IV tumors (n = 27/37; 73.0%). Other factors influencing extent of resection include maximum tumor diameter (95%CI -4.22 - -1.38, p < 0.001), Lyon’s classification grade (95%CI -1.80 - -0.52, p < 0.001), positive IHC for GH (95%CI -0.997 - -0.15, p < 0.01), PRL (95%CI -0.70 - -0.11, p < 0.01), FSH (95%CI 0.16–0.57, p < 0.001), and LH (95%CI 0.21–0.62, p < 0.0001), (Fig. 1 ). Of 154 patients with preoperative visual impairment, 93 (60.4%) reported improvement postoperatively, and 40 (26.0%) reported no change. Data were unavailable for 14 patients. Complications Fifty-nine patients (33.5%) experienced at least one complication. The most common was transient DI, seen in 36 patients (20.5%), with 8 (4.5%) developing permanent DI. Among 126 patients with complete endocrine follow-up, 28 (22.2%) developed new anterior pituitary deficits postoperatively. Twelve patients (6.8%) developed postoperative hematomas with clinical presentation of mass effect or CSF circulation disturbances; 7 (4.0%) of them required reoperation. Additional complications are presented in Table 3 . Four patients died during the early postoperative period—one from sepsis and disseminated intravascular coagulation, the second due to intracerebral hemorrhage and hydrocephalus following tumor apoplexy, the third due to meningitis, and the fourth due to pulmonary embolism and pneumonia. Table 3 Complications of the surgery Variables Number of patients Percentage of patients Transient DI 36 20.5% Hematoma 12 6.8% Hyponatremia 8 4.5% Worsening of vision 7 4.0% Hydrocephalus 6 3.4% CSF leak 5 2.8% Meningitis 5 2.8% Cranial nerves paralysis 4 2.3% Epistaxis 4 2.3% Stroke 4 2.3% Death 4 2.3% SIADH 3 1.7% Anosmia 2 1.1% Table 4 A summary of studies with GPAs treated by EETS showing Knosp scale grades and resection rates Study Number of patients Knosp 0 or I, N (%) Knosp II, N (%) Knosp III, N (%) Knosp IV, N (%) GTR, N (%) NTR, N (%) STR, N (%) PR, N (%) Ceylan et al ., 2022 [ 9 ] 205 87 (42.4%) 118 (57.6%) 72 (35.1%) 81 (39.5%) 52 (25.4%) 0 (0%) Chibbaro et al ., 2021 [ 14 ] 96 54 (56.3%) 19 (19.8%) 9 (9.4%) 14 (14.6%) 34 (35.4%) 12 (12.5%) 50 (52.1%) 0 (0%) Micko et al ., 2022 [ 6 ] 64 17 (26.7%) 47 (73.4%) 18 (28.1%) 0 (0%) 34 (53.1%) 12 (18.8%) Elshazly et al ., 2018 [ 10 ] 55 2 (3.6%) 15 (27.3%) 21 (38.2%) 17 (30.9%) 24 (43.6%) 26 (47.2%) 5 (9.1%) 0 (0%) Koutourousiou et al ., 2013 [ 23 ] 54 (108 cavernous sinuses) 18 (16.7% cavernous sinuses 24 (22.2%) cavernous sinuses 35 (32.4% cavernous sinuses 31 (28.7%) cavernous sinuses 11 (20.4%) 36 (66.7%) 7 (13.0%) De Paiva Neto et al ., 2010 [ 30 ] 51 14 (27.5%) 2 (3.9%) 14 (27.5%) 17 (33.3%) 21 (41.2%) 10 (19.6%) 20 (39.2%) 0 (0%) Gondim et al ., 2014 [ 11 ] 50 20 (40.0%) 14 (28.0%) 8 (16.0%) 8 (16%) 19 (38.0%) 9 (18.0%) 0 (0%) 22 (44.0%) Rahimli et al ., 2021 [ 58 ] 44 28 (63.6%) 16 (36.4%) 28 (63.6%) 10 (22.7%) 6 (13.6%) Our study 176 90 (51.1%) 49 (27.8%) 37 (21.0%) 74 (42.0%) 76 (43.2%) 26 (14.8%) Postoperative hypopituitarism requiring hormone replacement therapy was present in 78 patients. Among these 78 patients in 28 a new postoperative hypopituitarism was diagnosed and the rest experienced persistent hypopituitarism which was not alleviated by the surgery. Seventeen patients (9.7%) required reoperation for surgical complications: 7 for hematoma (41.2%), 6 for hydrocephalus (35.3%), and 3 for CSF leak (17.7%). Twenty-eight patients (15.9%) experienced tumor recurrence. Factors associated with recurrences include positive IHC for PRL (95%CI -0.34 - -0.03, p < 0.05) and ACTH (95%CI 0.02–0.49, p < 0.05), and the occurrence of postoperative CSF leak (95%CI 0.13–0.78, p < 0.01), (Fig. 2 ). The median progression-free survival (PFS) was 63 months. Patients who underwent GTR or STR (64 and 65 months respectively) had longer PFS compared to patients who underwent PR (59 months) – Fig. 3 . Four underwent staged resections due to complex anatomy precluding complete resection in a single procedure. Twelve patients (6.8%) were readmitted within one month, mainly for CSF leak (n = 4) or hydrocephalus (n = 3). Eighteen patients (10.2%) underwent reoperation due to tumor regrowth, at a mean of 46.5 months postoperatively. There was no statistically significant association between Knosp grade and complication rate (Fisher’s exact test, p = 0.076) – Supplementary Table 3. Factors influencing the evidence of disease after treatment include maximum tumor diameter (95%CI 1.35–3.23, p < 0.00001), positive IHC for GH (95%CI 0.15–0.74, p < 0.01), PRL (95%CI 0.13–0.54, p < 0.01), FSH (95%CI -0.42 – -0.14, p < 0.001), and LH (95%CI -0.40 – -0.11, p < 0.001), and invasiveness (95%CI 0.05–0.65, p < 0.0001), (Fig. 4 ). Surgical learning curve across the observation period We divided our cohort into into four groups basing on dates of first surgeries – group 1 (2007–2011), group 2 (2012–2015), group 3 (2016–2019), and group 4 (2020–2023). The extent of resection improved over time, with GTR/NTR rates increasing from below 30% in 2007–2011 to over 50% in 2016–2019. Partial resections declined steadily, while subtotal resections remained the most frequent category. Complication profiles changed over time, with an increase in postoperative DI from 11% to nearly 30% in the most recent period, which is probably due to more aggressive resections and more significant postoperative displacement of hypothalamic and posterior pituitary structures. In contrast, other complications, such as CSF leaks, hematomas, and epistaxis, became less frequent over time; meningitis, however, occurred sporadically without a discernible temporal trend. Discussion GPAs represent a unique surgical challenge due to their substantial size and complex anatomical relationships [ 17 ]. In this study, we analyzed 176 patients with GPAs treated via EETS in a single center, assessing the clinical features, histopathological characteristics, surgical outcomes, and safety of this approach. Consistent with previous studies, most patients in our cohort were male [2; 11; 18]. The majority of GPAs were non-functioning (88.1%), aligning with prior reports indicating that 66–78% of GPAs are non-functioning PitNET [8; 17–19]. Given their size, GPAs typically present with mass effect symptoms, particularly visual disturbances from optic chiasm compression—reported in ~ 70% of patients [ 8 ]. In our cohort, the rate was even higher (87.5%), consistent with findings by other authors [17; 20]. Pituitary hormone deficiencies are common in GPAs, with preoperative rates between 70% and 80% [9; 21]. In our cohort, 61.9% had preoperative hypopituitarism. Gonadotroph adenomas were the predominant histopathological subtype, as expected for this tumor class [ 22 ]. EETS remains the preferred surgical route for most GPAs, offering better resection rates than transcranial approaches. Reported GTR rates for EETS range from 20.4–47.2% [21; 23]. Komotar et al. (2012) demonstrated significantly higher GTR rates for EETS (47.2%) compared to transcranial surgery (9.6%) [ 21 ]. Nonetheless, craniotomy may be necessary in cases of poor sphenoid sinus pneumatization, vascular anomalies, lateral or posterior tumor extension, or fibrous consistency [ 24 ]. Craniotomy can also offer benefits in selected Knosp grade IV cases. Guan et al . (2022) reported a 26.2% GTR rate in Knosp grade IV tumors treated via transcranial surgery [ 25 ]. Various factors affect the extent of resection (Table 5 ). One of the most important among them is Knosp scale grade [ 26 ]. In our series, GTR was achieved in twice as many patients with Knosp grade II tumors compared to grade III, and only 1% of grade IV tumors achieved GTR. These findings support previous reports indicating significantly higher GTR rates in Knosp grades 0–II than in III–IV [ 27 ]. Gondim et al. (2014) similarly observed that Knosp grades III and IV were more frequently associated with STR [ 11 ]. While we did not distinguish between grades IIIA and IIIB, prior studies show that GTR is more feasible in IIIA tumors [27; 28]. Grade IV tumors, due to cavernous sinus invasion, are particularly difficult to fully resect [ 29 ]. Table 5 A summary of studies with GPAs treated by EETS showing factors limiting extent of resection Study Factors limiting extent of resection Yang et al ., 2024 [ 37 ] 1. Tumor volume 2. Maximum diameter 3. Multilobulated shape 4. Cavernous sinus invasion 5. Extension of the tumor to posterior fossa 6. Extent of suprasellar lateral extension Chen et al ., 2022 [ 18 ] 1. Maximum diameter 2. Knosp grade Patel et al ., 2022 [ 59 ] 1. Preoperative tumor volume 2. Knosp grade Ceylan et al ., 2021 [ 9 ] 1. Suprasellar part of the tumor exceeding 2 cm in height 2. Cavernous sinus invasion 3. Extension of the tumor to anterior fossa, posterior fossa, and inferior wall of the lateral ventricle 4. Multilobulated shape 5. x/y ratio exceeding 1.5 Chibbaro et al ., 2021 [ 14 ] 1. Cavernous sinus invasion 2. Suprasellar part of the tumor exceeding 2.5 cm in height 3. Fibrous consistence 4. Maximum diameter Peto et al ., 2020 [ 33 ] 1. Extent of anteroposterior and retrosellar extension 2. High Zurich score Gondim et al ., 2013 [ 11 ] 1. Cavernous sinus invasion Koutourousiou et al ., 2013 [ 23 ] 1. Multilobulated shape 2. Extension of the tumor in the coronal plane 3. Knosp grade IV De Paiva Neto et al. , 2010 [ 30 ] 1. Cavernous sinus invasion Beyond Knosp grade, cavernous sinus invasion itself is a major limiting factor for resection [ 30 ]. De Paiva Neto et al. (2010) reported GTR rates of 90% in non-invasive tumors but only 9.6% in invasive ones [ 30 ]. Tumors with cavernous sinus invasion also tend to be larger [ 31 ]. Extended EETS, including posterior ethmoidectomy, may enhance exposure and facilitate resection in such cases [ 32 ]. Although cavernous sinus invasion often limits GTR, Koutourousiou et al. (2013) found that tumor shape and middle fossa extension — rather than size or invasion — were more predictive of incomplete resection [ 23 ]. Other anatomical predictors include suprasellar anteroposterior distance, retrosellar extension, and higher Zurich scores [ 33 ]. GPA resection is also complicated by tumor consistency and capsular anatomy. Most PAs are soft, but 5–13% can be fibrous [ 34 ]. Fibrous tumors are linked to higher rates of STR and increased surgical risk [27; 34]. In our cohort, 11.9% of tumors were fibrous —comparable to prior reports — but we did not observe a correlation between consistency and extent of resection. This may be due to our routine use of extracapsular dissection and extended approaches. The capsule is composed of peritumoral cells, microvascular structures and reticulin [ 9 ]. Capsule enclosing GPAs is often thicker than capsule enclosing smaller tumors, due to greater compression exerted by the tumor [9; 35]. However, capsule removal may be avoided to prevent cerebrospinal fluid (CSF) leakage [9; 35]. Another structure delineating the tumor from healthy tissues called pseudocapsule is composed of compressed reticulin and located between the tumor and pituitary gland [ 36 ]. Pseudocapsule can guide safe dissection, but its disruption may hinder complete resection [ 36 ]. Various studies confirmed multilobulated shapes of GPAs negatively impact the extent of resection [9; 23; 37]. Such growth pattern becomes more evident with increasing vertical suprasellar expansion and may prevent descending of the suprasellar part [ 38 ]. Multilobulated shape might also suggest perforation of sellar diaphragm or subarachnoid invasion [ 38 ]. The extent of resection is also affected by the neurosurgeon’s level of experience, which typically improves with progression along the learning curve [ 39 ]. Our data suggest that surgical experience improves resection rates over time, with GTR/NTR achieved in more than half of cases after 2016, compared to less than one-third in the earliest time period. This is consistent with prior reports [ 42 ] highlighting the influence of the learning curve in endoscopic pituitary surgery. The rising incidence of postoperative DI in later years likely reflects a more aggressive approach affecting the hypothalamo-hypophyseal tract. However, the rate of permanent DI is still low (4.5%). We found that CSF leak and hemorrhagic complication rates declined over time, suggesting that the development of surgical skills was associated with improvements in both the extent of resection and overall safety. Surgical management of GPAs is associated with a higher complication rate compared to non-giant pituitary adenomas [ 17 ]. EETS for GPAs carries a complication rate between 11.1% and 20.6% (Table 6 ) [17; 40], similar to that observed in smaller PitNETs (12.1–19.3%) [41; 42]. Hypopituitarism is the most frequent complication, with incidence ranging from 13.7–76.0% (Table 6 ) [11; 30]. In our cohort 22.2% of patients experienced new postoperative hypopituitarism. Recovery of pituitary function postoperatively is more common than new onset hypopituitarism [ 43 ]. The risk is influenced by tumor size, consistency, resection extent, and number of surgeries [ 44 ]. Table 6 A summary of studies with GPAs treated by EETS showing complications Study Number of patients New post-operative hypo pituita rism N, (%) CSF leak N, (%) Perma nent DI N, (%) Meningitis N, (%) ICA injury N, (%) Hematoma N, (%) Stroke N, (%) Worsening of vision N, (%) Death N, (%) Ceylan et al ., 2022 [ 9 ] 205 46 (22.4%) 8 (3.9%) 16 (7.8%) 7 (3.4%) 0 (0%) 8 (3.9%) 0 (0%) 4 (2.4%) 3 (1.5%) Chibbaro et al ., 2021 [ 14 ] 96 0 (0%) 7 (7.3%) 0 (0%) 7 (7.3%) 0 (0%) 2 (2.1%) 0 (0%) 1 (1.0%) 0 (0%) Micko et al ., 2022 [ 6 ] 64 11 (17.2%) 9 (14.1%) 4 (6.3%) 4 (6.3%) 0 (0%) 0 (0%) 4 (6.3%) 2 (3.1%) 0 (0%) Elshazly et al ., 2018 [ 10 ] 55 8 (14.5%) 1 (1.8%) 4 (7.3%) 0 (0%) 0 (0%) 0 (0%) 1 (1.8%) 1 (1.8%) 0 (0%) Koutourousiou et al ., 2013 [ 23 ] 54 (108 cavernous sinuses) 9 (16.7%) 9 (16.7%) 5 (9.3%) 3 (5.6%) 0 (0%) 0 (0%) 1 (1.8%) 2 (3.7%) 0 (0%) De Paiva Neto et al ., 2010 [ 30 ] 51 7 (13.7%) 1 (2.0%) 5 (9.8%) 0 (0%) 0 (0%) 2 (3.9%) 0 (0%) 0 (0%) 0 (0%) Gondim et al ., 2014 [ 11 ] 50 18 (36.0%) 4 (8.0%) 5 (10.0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.0%) 2 (4.0%) Rahimli et al ., 2021 [ 58 ] 44 0 (0%) 5 (11.4%) 4 (9.1%) 1 (2.3%) 2 (4.5%) 0 (0%) 0 (0%) 0 (0%) 2 (4.5%) Our study 176 28/126 22.2% 5 (2.8%) 8 (4.5%) 5 (2.8%) 0 (0%) 12 (6.8%) 4 (2.3%) 7 (4.0%) 4 (2.3%) DI, often transient, is another notable complication, with permanent DI reported in up to 10% of cases [11; 14]. DI following EETS is neurogenic and results from hypothalamic or infundibular injury and impaired vasopressin transport [ 45 ]. In our cohort 20.5% of the patients had transient DI which became permanent in 4.5%. Transient DI was the most common complication in our patients. Another important complication of GPAs includes postoperative CSF leaks. Postoperative CSF leaks occur in 1.8–16.7% of patients operated for GPAs [10; 23], with risk factors including lobular tumor shape, thin arachnoid-only diaphragmatic roof, high BMI, prior surgeries, and intraoperative CSF leak [ 46 – 48 ] Capsule preservation may reduce CSF leak risk [ 35 ]. Postoperative sellar hematoma is a rare complication of EETS for pituitary adenomas occurring in 1.5% of patients [ 49 ]. Significant risk factors include tumor diameter ≥ 30mm, suprasellar extension, tumor volume, cavernous sinus invasion, gonadotroph type of the tumor, use of antiplatelet drugs, and elevated body mass index [ 49 ]. In tumors with transdiaphragmatic extensions the risk of a postoperative hematoma is also increased [ 17 ]. Such tumors may not be well encapsulated with small perforating arteries running along the pseudocapsule [ 17 ]. We observed a relatively high rate of postoperative hematomas requiring treatment in our cohort (6.8%), surgical evacuation was necessary in 7 patients (4.0%). The rate of hematomas decreased after we started to perform extended EETS approaches routinely. Rhinologic complications are rare after EETS, but hyposmia can occur, especially with excessive coagulation of the superior and middle turbinates [41; 50]. We observed two such cases in our series. PitNETs morphology and anatomical relationships are described using various grading systems proposed by Hardy et al. [ 38 ], Wilson et al . [ 51 ], Knosp et al. (Knosp scales) [ 52 ], Goel et al. (Giant tumors grading) [ 53 ], Edal et al. (SIPAP classification) [ 54 ], among others. In 2013 Trouillas et al. proposed another grading scale - a five-tiered prognostic clinicopathological classification of PitNETs (Lyon’s clinicopathologic classification), which predicts the probability of tumor progression and the likelihood of achieving complete remission [ 16 ]. This classification offers improved prognostication over the WHO system by incorporating proliferation indices and invasiveness [16; 55]. In our series, patients with grade 2b tumors had worse outcomes, consistent with original findings, though the overall recurrence risk was lower compared to other studies. The most recent classification of PitNETs was proposed in 2024 by Ho et al. , and assesses the disease severity, prognosis, and effects of therapy [56; 57]. There are several limitations to this study. First, it is a retrospective analysis with some patients lost to follow-up. Second, the definition of GPAs is arbitrary and depends on the tumor’s maximum diameter, which may be prone to measurement error and introduce selection bias. Finally, the patients were treated over an extended time period, during which the surgeon’s growing experience and learning curve may have influenced the outcomes. Conclusions Overall, our findings confirm that EETS is a safe and effective treatment for GPAs, achieving satisfactory resection rates in most patients. Despite anatomical challenges and a moderate risk of complications, EETS enables durable control of tumor growth with acceptable morbidity. Declarations The authors declare no conflicts of interests. No funding was received for conducting this study. All patients gave informed consent for using their data in this study. The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Maria Sklodowska-Curie Institute—Oncology Center in Warsaw, Poland (approval decision 86/2022). Author Contribution Concept & Design: JK, BB; Literature Search: JK, BB; Data Extraction: BB, JK, MM; Statistical Analysis: BB, SB; Interpretation of Data: JK, BB, MM, SB; Drafting of Manuscript: BB, JK; Critical Revision: JK, MM, TM; Supervision: JK; Project Administration: TM Data Availability Data is provided within the manuscript or supplementary information files, raw data in excel files can be uploaded on request. References Sivakumar, W., Chamoun, R., Nguyen, V., & Couldwell, W. T. (2011). Incidental pituitary adenomas. Neurosurg Focus , 31 (6), E18. https://doi.org/10.3171/2011.9.Focus11217 Gaia, F., Gonzalez-Reyes, L., Belfort, M. A., Medeiros, R. G. B., Bendinid, J. D., & Barbosa, G. F. (2022). 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Buchalska","email":"data:image/png;base64,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","orcid":"","institution":"The Maria Sklodowska-Curie National Research Institute of Oncology","correspondingAuthor":true,"prefix":"","firstName":"Barbara","middleName":"","lastName":"Buchalska","suffix":""},{"id":514822643,"identity":"eb9e68c4-9c94-458d-b642-ebe3b3264c03","order_by":2,"name":"Maria Maksymowicz","email":"","orcid":"","institution":"The Maria Sklodowska-Curie National Research Institute of Oncology","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Maksymowicz","suffix":""},{"id":514822646,"identity":"6f75613f-49c6-4c94-8ccf-787c391a39bd","order_by":3,"name":"Szymon Baluszek","email":"","orcid":"","institution":"The Maria Sklodowska-Curie National Research Institute of Oncology","correspondingAuthor":false,"prefix":"","firstName":"Szymon","middleName":"","lastName":"Baluszek","suffix":""},{"id":514822647,"identity":"7307c3a4-fe20-4155-b469-e30c77bdeec0","order_by":4,"name":"Tomasz Mandat","email":"","orcid":"","institution":"The Maria Sklodowska-Curie National Research Institute of Oncology","correspondingAuthor":false,"prefix":"","firstName":"Tomasz","middleName":"","lastName":"Mandat","suffix":""}],"badges":[],"createdAt":"2025-09-07 17:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7557934/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7557934/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11102-025-01596-z","type":"published","date":"2025-11-02T15:57:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":91507728,"identity":"baadf346-9491-46cc-98b9-197fb9d5b300","added_by":"auto","created_at":"2025-09-17 08:35:41","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":268366,"visible":true,"origin":"","legend":"\u003cp\u003eUnivariate and multivariate analyses of the factors associated with the extent of resection.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7557934/v1/0036b968e9681afa9022f6aa.jpeg"},{"id":91507729,"identity":"0e7d796b-7154-4f41-8ea1-a7e890c12e08","added_by":"auto","created_at":"2025-09-17 08:35:41","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":217939,"visible":true,"origin":"","legend":"\u003cp\u003eUnivariate and multivariate analyses of the factors associated with recurrences.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7557934/v1/fe90381089222808111a668a.jpeg"},{"id":91510260,"identity":"340cf46f-9689-4bb2-9599-304244523bf1","added_by":"auto","created_at":"2025-09-17 08:43:41","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":179909,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival (PFS) in patients with gross total (GTR), subtotal (STR), and partial resection (PR).\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7557934/v1/896f8cfe9c9e1a006526e305.jpeg"},{"id":91507727,"identity":"ff40c4f0-1f17-489b-97ae-8b141f016aa4","added_by":"auto","created_at":"2025-09-17 08:35:41","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":134763,"visible":true,"origin":"","legend":"\u003cp\u003eUnivariate and multivariate analyses of the factors associated with the evidence of disease.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7557934/v1/4b726ef7deda04a1cccfff5e.png"},{"id":95040645,"identity":"a805651b-66d8-4535-b522-2690f532d321","added_by":"auto","created_at":"2025-11-03 16:10:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2336872,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7557934/v1/c0dccde6-67ac-461e-ba46-d2e1b4ad2ff6.pdf"},{"id":91507720,"identity":"8558eb95-a54c-4d07-8144-fb717faa5934","added_by":"auto","created_at":"2025-09-17 08:35:40","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":18932,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-7557934/v1/0d8a13ebbacb3fd45f8a7b89.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Endoscopic endonasal resection of giant pituitary neuroendocrine tumors - case series from the referral pituitary center","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePituitary neuroendocrine tumors (PitNETs), previously known as pituitary adenomas, comprise 10\u0026ndash;15% of all brain tumors, and are the most common neuroendocrine tumors of the central nervous system [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There are different definitions of giant pituitary adenomas (GPAs) using morphological tumor parameters e.g. linear diameters, volumetric assessment, and anatomical extent [\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Practically, the most commonly used definition is one that describes a tumor with a maximum diameter of 40 mm or more [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. GPAs account for approximately 10% of surgically treated pituitary tumors [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Due to their large volume and high rates of extrasellar invasion, surgical treatment remains challenging [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Complete resection of GPAs is often not achieved, and they tend to recur more frequently than other PitNETs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Treatment of GPAs is more frequently associated with serious complications [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Traditionally, transcranial and transsphenoidal microscopic surgical approaches have played a central role in the management of GPAs [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, in the past two decades, endoscopic endonasal transsphenoidal surgery (EETS) has been increasingly used [9; 13; 14]. The use of EETS for GPA treatment is associated with improved outcomes, including a greater extent of resection and lower morbidity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This study aimed to review the surgical outcomes in a series of patients with GPAs operated using the endoscopic endonasal approach in the referral pituitary center.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eWe retrospectively analyzed 176 patients with GPAs who underwent transsphenoidal endoscopic surgery at The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between 2007 and 2023. During this period 2323 patients with pituitary adenomas were treated surgically at our center, with GPAs comprising 7.6% of cases(n\u0026thinsp;=\u0026thinsp;176/2323). GPAs also accounted for 14.0% of all macroadenomas operated at our center (n\u0026thinsp;=\u0026thinsp;176/1261). All procedures were performed by the same dedicated neurosurgical team.\u003c/p\u003e\u003cp\u003eInclusion criteria included age\u0026thinsp;\u0026ge;\u0026thinsp;18 years, histologically confirmed diagnosis of PitNET, maximum tumor diameter\u0026thinsp;\u0026ge;\u0026thinsp;40 mm, and surgical treatment using the EETS technique.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eClinical and demographic data were obtained from patient medical records, including age, sex, clinical presentation, hospital stay duration, and follow-up period. Tumor characteristics included maximum dimensions (in mm), consistency, invasive features, and pathological results. Classification was based on the 2022 WHO classification of pituitary tumors [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and the Lyon\u0026rsquo;s clinicopathological classification [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSurgical data included the extent of tumor resection\u0026mdash;gross total resection (GTR), near-total resection (NTR, \u0026ge;\u0026thinsp;95%), subtotal resection (STR, \u0026ge;\u0026thinsp;80%), and partial resection (PR, \u0026lt;\u0026thinsp;80%)\u0026mdash;as well as the method of sellar reconstruction. Additional data were collected on postoperative complications, reoperations, and hospital readmissions. The permanent arginine vasopressin deficiency (diabetes insipidus, DI) was defined as DI persisting for \u0026ge;\u0026thinsp;6 months. All patients underwent comprehensive pre- and postoperative evaluations, including visual field testing, neurological examination (with emphasis on cranial nerve assessment), and hormonal blood analysis.\u003c/p\u003e\u003cp\u003ePreoperatively, each patient received a pituitary magnetic resonance imaging (MRI) scan to confirm tumor localization, visual field testing, a neurological examination, and assessment of anterior pituitary hormone levels, including growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).\u003c/p\u003e\u003cp\u003ePostoperative assessment included a head computed tomography (CT) scan within 24 hours of surgery to evaluate the extent of resection and exclude intracranial hemorrhagic complications, and a repeat hormonal analysis. Patients with postoperative complications underwent additional CT scans as needed. Follow-up imaging included a pituitary MRI within 2 to 3 months after surgery, repeated every year for 3 years, then repeated every 2 years, and additionally as clinically indicated to monitor for tumor progression. Tumor size and Knosp grade were assessed radiologically. Progression was defined as an increase in tumor volume of \u0026ge;\u0026thinsp;20%.\u003c/p\u003e\u003cp\u003eFollow-up data were obtained through outpatient clinic records and structured telephone interviews, with a response rate of 71.6% (126 of 176 patients). Patient vital status was verified via a government-maintained death registry.\u003c/p\u003e\u003cp\u003eTo evaluate the influence of accumulated experience, we divided the study period (2007\u0026ndash;2023) into four consecutive intervals \u0026ndash; the first spanning 5 years, followed by three subsequent 4-year intervals. This subdivision enabled longitudinal assessment of surgical outcomes and complication rates over time.\u003c/p\u003e\u003cp\u003eTumor samples collected intraoperatively were fixed in 10% buffered formalin, embedded in paraffin, and stained with hematoxylin and eosin (H\u0026amp;E). Immunohistochemistry (IHC) was performed using primary antibodies against anterior pituitary hormones: GH, PRL, ACTH, TSH, FSH, LH, and α-SU (alpha-subunit). In cases requiring more detailed analysis, IHC was performed for the pituitary transcription factors: PIT-1, TPIT, and SF-1. Antibodies were sourced from Thermo Scientific, Dako, NeoMarkers, Novocastraor BIO-RAD companies. Staining procedures were made on paraffin sections using the EnVision\u003csup\u003eTM\u003c/sup\u003eFlexVisualization System with DAB (3,3\u0026rsquo; \u0026ndash; diaminobenzidine) as chromogen (K8000, Dako/Agilent). Ki-67 proliferation index was evaluated using Dako antibodies.\u003c/p\u003e\u003cp\u003eElectron microscopy (EM) was performed in 168 patients. Tissue samples were fixed in 2.5% glutaraldehyde and postfixed in 1% osmium tetroxide, dehydrated in ethanol and propylene oxide, then embedded in epoxy resin (Epon 812). Ultrathin sections were counterstained with uranyl acetate and lead citrate and analyzed using a Philips CM120 BioTWIN transmission electron microscope.\u003c/p\u003e\n\u003ch3\u003eSurgical Approach\u003c/h3\u003e\n\u003cp\u003eAll surgeries were performed using the EETS technique by the same neurosurgeon experienced in pituitary surgery. A standard endoscopic approach was used in the majority of cases, either via a one-and-a-half nostril approach (n\u0026thinsp;=\u0026thinsp;54/176; 30.7%), or a binostril approach (n\u0026thinsp;=\u0026thinsp;122/176; 69.3%). In 11 patients (6.3%), an extended transtubercular or transplanar approach was used to address selected suprasellar tumor extensions.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eData analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics, including mean, median, standard deviation, minimum, and maximum values, were calculated. Fisher\u0026rsquo;s exact tests and survival analyses were performed using GraphPad software. R (v4.2.2) was utilized for univariate and multivariate analyses. Statistical inference was performed with generalized linear model (glm) and Cox proportional hazards model (coxph). In multivariate analysis L1 regularization with glmnet was implemented to control for the number of input features. A significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was assumed for all analyses.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eGeneral characteristics\u003c/h2\u003e\u003cp\u003eMost patients were men (n\u0026thinsp;=\u0026thinsp;110; 62.5%), and the mean age of the patients was 57.0 +-13.2 years (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean follow-up duration was 7.5 years ranging from 0 to 16 years. The average postoperative hospital stay was 7.1 days (range: 2\u0026ndash;30 days). The most common initial symptoms were were visual disturbances (n\u0026thinsp;=\u0026thinsp;154; 87.5%), followed by the endocrine disorders (n\u0026thinsp;=\u0026thinsp;104; 59.1%), neurological deficits (n\u0026thinsp;=\u0026thinsp;44; 25.0%), headache (n\u0026thinsp;=\u0026thinsp;19; 10.8%) and symptomatic pituitary apoplexy (n\u0026thinsp;=\u0026thinsp;18; 10.2%). Endocrine disorders included symptomatic hypopituitarism (n\u0026thinsp;=\u0026thinsp;86; 48.9%), hyperprolactinemia (n\u0026thinsp;=\u0026thinsp;51; 29.0%), acromegaly (n\u0026thinsp;=\u0026thinsp;5; 2.8%), and Cushing\u0026rsquo;s disease (n\u0026thinsp;=\u0026thinsp;3; 1.7%). Three patients were asymptomatic, and their GPAs were discovered incidentally during workups for unrelated conditions. At the time of analysis 160 patients were alive (90.9%). Four patients died due to complications (2.3%). The remaining patients had died due to causes unrelated to GPA.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGeneral characteristics of the patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue/number of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercentage of patients\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emean age [years]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emedian age [years]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erange [years]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u0026ndash;81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFollow-up time\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emean [years]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emedian [years]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erange [years]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u0026ndash;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of days spent at the hospital after the surgery\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emean\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erange\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u0026ndash;30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical presentation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003evisual defects\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e154\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e87.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eendocrine defects, including:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e104\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehypopituitarism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehyperprolactinemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eacromegaly\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCushing\u0026rsquo;s disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eother neurological deficits\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eheadache\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epituitary apoplexy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003enon-significant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eKnosp scale grade\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaximum tumor diameter\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emean [mm]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emedian [mm]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erange [mm]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40\u0026ndash;90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConsistency of the tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esoft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efibrous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFunctional status of the tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efunctioning\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003enon-functioning\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInvasiveness of the tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003einvasive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecavernous sinus invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esphenoid sinus invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esellar diaphragm invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esella turcica invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eclivus invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003einvasion to the third ventricle\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esubarachnoidal space invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003enon-invasive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTumor characteristics\u003c/h3\u003e\n\u003cp\u003eThe mean maximal tumor diameter was 46.2 millimeters (range: 40\u0026ndash;90 mm) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Most tumors were non-functioning (n\u0026thinsp;=\u0026thinsp;155; 88.1%), while 21 cases (11.9%) were hormonally active. Tumor consistency was described as soft in 155 patients (88.1%) and fibrous in 21 patients (11.9%). All tumors had suprasellar extension.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSurgical characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercentage of patients\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eResection\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGTR and NTR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSTR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgical endoscopic approach\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStandard\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtended\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eReconstruction of sella with a fat tissue graft\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntraoperative CSF leak\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBiopsy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRecurrence of the tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eResidual disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eReoperation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients without reoperations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEarly reoperation due to complications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDue to tumor regrowth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgery performed in two parts\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of patients readmitted to the hospital\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of readmissions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean number of readmissions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eKnosp grade distribution was as follows: grade II in 90 patients (51.1%), grade III in 49 patients (27.8%), and grade IV in 37 patients (21.0%). There was a statistically significant association between gender and Knosp grade (Fisher\u0026rsquo;s exact test, p\u0026thinsp;=\u0026thinsp;0.018). More women had grade III or IV tumors (n\u0026thinsp;=\u0026thinsp;41/66; 62.1%) compared to men (n\u0026thinsp;=\u0026thinsp;45/110; 40.9%).\u003c/p\u003e\u003cp\u003eMost GPAs were invasive (n\u0026thinsp;=\u0026thinsp;130; 73.8%). The most common direction of invasion was into the cavernous sinus (n\u0026thinsp;=\u0026thinsp;80; 45.5%), and the least common was into the subarachnoid space (n\u0026thinsp;=\u0026thinsp;7; 4.0%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There was also a significant association between tumor invasiveness and Knosp grade (Fisher\u0026rsquo;s exact test, p\u0026thinsp;=\u0026thinsp;0.0009). All grade IV tumors (n\u0026thinsp;=\u0026thinsp;37/37) and 75.5% of grade III tumors (n\u0026thinsp;=\u0026thinsp;37/49) assessed basing on MRI were classified as invasive after an intraoperative evaluation.\u003c/p\u003e\u003cp\u003eThe most common histopathological diagnosis was gonadotroph adenoma (n\u0026thinsp;=\u0026thinsp;120; 68.2%), including oncocytic variants (n\u0026thinsp;=\u0026thinsp;27/120; 22.5%). Nineteen patients initially diagnosed with null cell adenomas (10.8%) basing on standard immunohistochemical stainings were reclassified as gonadotroph adenomas based on ultrastructural and transcription factor analysis (Supplementary Table\u0026nbsp;1). According to Lyon\u0026rsquo;s clinicopathological classification, 40 patients (22.7%) had grade 1a tumors, 7 (4.0%) had grade 1b, 111 (63.1%) had grade 2a, and 18 (10.2%) had grade 2b tumors. The proportion of proliferative tumors was similar between invasive (14.9%) and non-invasive (14.0%) cases.\u003c/p\u003e\n\u003ch3\u003eSurgical results\u003c/h3\u003e\n\u003cp\u003eThe extent of resection was subtotal (STR) in 77 patients (43.7%), gross total or near-total (GTR/NTR) in 73 (41.5%), and partial resection (PR) in 26 (14.8%). In 110 cases (62.5%), the sellar floor was reconstructed using fat grafts, either due to intraoperative cerebrospinal fluid (CSF) leaks (n\u0026thinsp;=\u0026thinsp;90/110; 81.8%) or significant herniation of the diaphragm/suprasellar cisterns (n\u0026thinsp;=\u0026thinsp;20/110; 18.2%). Five patients had intraoperative CSF leak managed without using sellar floor reconstruction with fat grafts.\u003c/p\u003e\u003cp\u003eKnosp grade was significantly associated with extent of resection (Fisher\u0026rsquo;s exact test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). GTR/NTR was most common in patients with grade II tumors (n\u0026thinsp;=\u0026thinsp;49/73; 67.1%), followed by grade III (n\u0026thinsp;=\u0026thinsp;23/73; 31.5%) and grade IV (n\u0026thinsp;=\u0026thinsp;1/73; 1.4%) tumors (Supplementary Table\u0026nbsp;2). STR was predominant among patients with grade IV tumors (n\u0026thinsp;=\u0026thinsp;27/37; 73.0%).\u003c/p\u003e\u003cp\u003eOther factors influencing extent of resection include maximum tumor diameter (95%CI -4.22 - -1.38, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), Lyon\u0026rsquo;s classification grade (95%CI -1.80 - -0.52, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), positive IHC for GH (95%CI -0.997 - -0.15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), PRL (95%CI -0.70 - -0.11, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), FSH (95%CI 0.16\u0026ndash;0.57, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and LH (95%CI 0.21\u0026ndash;0.62, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of 154 patients with preoperative visual impairment, 93 (60.4%) reported improvement postoperatively, and 40 (26.0%) reported no change. Data were unavailable for 14 patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eComplications\u003c/h2\u003e\u003cp\u003eFifty-nine patients (33.5%) experienced at least one complication. The most common was transient DI, seen in 36 patients (20.5%), with 8 (4.5%) developing permanent DI. Among 126 patients with complete endocrine follow-up, 28 (22.2%) developed new anterior pituitary deficits postoperatively. Twelve patients (6.8%) developed postoperative hematomas with clinical presentation of mass effect or CSF circulation disturbances; 7 (4.0%) of them required reoperation. Additional complications are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Four patients died during the early postoperative period\u0026mdash;one from sepsis and disseminated intravascular coagulation, the second due to intracerebral hemorrhage and hydrocephalus following tumor apoplexy, the third due to meningitis, and the fourth due to pulmonary embolism and pneumonia.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComplications of the surgery\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercentage of patients\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTransient DI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHematoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHyponatremia\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWorsening of vision\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHydrocephalus\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.4%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCSF leak\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMeningitis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCranial nerves paralysis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEpistaxis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStroke\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDeath\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSIADH\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAnosmia\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eA summary of studies with GPAs treated by EETS showing Knosp scale grades and resection rates\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eKnosp 0 or I, N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eKnosp II, N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eKnosp III, N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eKnosp IV, N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eGTR,\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNTR, N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSTR, N (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003ePR, N (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCeylan\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2022\u003c/b\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e205\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e87 (42.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e118 (57.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e72 (35.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e81 (39.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e52 (25.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChibbaro\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2021\u003c/b\u003e [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (56.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (19.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9 (9.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14 (14.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34 (35.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e50 (52.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMicko\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2022\u003c/b\u003e [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e17 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e47 (73.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 (28.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e34 (53.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e12 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eElshazly\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2018\u003c/b\u003e [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (3.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (27.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21 (38.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17 (30.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24 (43.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26 (47.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eKoutourousiou\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2013\u003c/b\u003e [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (108 cavernous sinuses)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (16.7% cavernous sinuses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (22.2%) cavernous sinuses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35 (32.4% cavernous sinuses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e31 (28.7%)\u003c/p\u003e\u003cp\u003ecavernous sinuses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11 (20.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e36 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e7 (13.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDe Paiva Neto\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2010\u003c/b\u003e [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (27.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14 (27.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e21 (41.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e10 (19.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e20 (39.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGondim\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2014\u003c/b\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (28.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (16.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8 (16%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19 (38.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9 (18.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e22 (44.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRahimli\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e.,\u003c/p\u003e\u003cp\u003e\u003cb\u003e2021\u003c/b\u003e [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003e28 (63.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16 (36.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e28 (63.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 (22.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e6 (13.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOur study\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e90 (51.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e49 (27.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37 (21.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e74 (42.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e76 (43.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e26 (14.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePostoperative hypopituitarism requiring hormone replacement therapy was present in 78 patients. Among these 78 patients in 28 a new postoperative hypopituitarism was diagnosed and the rest experienced persistent hypopituitarism which was not alleviated by the surgery. Seventeen patients (9.7%) required reoperation for surgical complications: 7 for hematoma (41.2%), 6 for hydrocephalus (35.3%), and 3 for CSF leak (17.7%).\u003c/p\u003e\u003cp\u003eTwenty-eight patients (15.9%) experienced tumor recurrence. Factors associated with recurrences include positive IHC for PRL (95%CI -0.34 - -0.03, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and ACTH (95%CI 0.02\u0026ndash;0.49, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the occurrence of postoperative CSF leak (95%CI 0.13\u0026ndash;0.78, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median progression-free survival (PFS) was 63 months. Patients who underwent GTR or STR (64 and 65 months respectively) had longer PFS compared to patients who underwent PR (59 months) \u0026ndash; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Four underwent staged resections due to complex anatomy precluding complete resection in a single procedure. Twelve patients (6.8%) were readmitted within one month, mainly for CSF leak (n\u0026thinsp;=\u0026thinsp;4) or hydrocephalus (n\u0026thinsp;=\u0026thinsp;3).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eEighteen patients (10.2%) underwent reoperation due to tumor regrowth, at a mean of 46.5 months postoperatively. There was no statistically significant association between Knosp grade and complication rate (Fisher\u0026rsquo;s exact test, p\u0026thinsp;=\u0026thinsp;0.076) \u0026ndash; Supplementary Table\u0026nbsp;3. Factors influencing the evidence of disease after treatment include maximum tumor diameter (95%CI 1.35\u0026ndash;3.23, p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001), positive IHC for GH (95%CI 0.15\u0026ndash;0.74, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), PRL (95%CI 0.13\u0026ndash;0.54, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), FSH (95%CI -0.42 \u0026ndash; -0.14, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and LH (95%CI -0.40 \u0026ndash; -0.11, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and invasiveness (95%CI 0.05\u0026ndash;0.65, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eSurgical learning curve across the observation period\u003c/h2\u003e\u003cp\u003eWe divided our cohort into into four groups basing on dates of first surgeries \u0026ndash; group 1 (2007\u0026ndash;2011), group 2 (2012\u0026ndash;2015), group 3 (2016\u0026ndash;2019), and group 4 (2020\u0026ndash;2023). The extent of resection improved over time, with GTR/NTR rates increasing from below 30% in 2007\u0026ndash;2011 to over 50% in 2016\u0026ndash;2019. Partial resections declined steadily, while subtotal resections remained the most frequent category. Complication profiles changed over time, with an increase in postoperative DI from 11% to nearly 30% in the most recent period, which is probably due to more aggressive resections and more significant postoperative displacement of hypothalamic and posterior pituitary structures. In contrast, other complications, such as CSF leaks, hematomas, and epistaxis, became less frequent over time; meningitis, however, occurred sporadically without a discernible temporal trend.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eGPAs represent a unique surgical challenge due to their substantial size and complex anatomical relationships [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this study, we analyzed 176 patients with GPAs treated via EETS in a single center, assessing the clinical features, histopathological characteristics, surgical outcomes, and safety of this approach.\u003c/p\u003e\u003cp\u003eConsistent with previous studies, most patients in our cohort were male [2; 11; 18]. The majority of GPAs were non-functioning (88.1%), aligning with prior reports indicating that 66\u0026ndash;78% of GPAs are non-functioning PitNET [8; 17\u0026ndash;19]. Given their size, GPAs typically present with mass effect symptoms, particularly visual disturbances from optic chiasm compression\u0026mdash;reported in ~\u0026thinsp;70% of patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In our cohort, the rate was even higher (87.5%), consistent with findings by other authors [17; 20]. Pituitary hormone deficiencies are common in GPAs, with preoperative rates between 70% and 80% [9; 21]. In our cohort, 61.9% had preoperative hypopituitarism. Gonadotroph adenomas were the predominant histopathological subtype, as expected for this tumor class [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEETS remains the preferred surgical route for most GPAs, offering better resection rates than transcranial approaches. Reported GTR rates for EETS range from 20.4\u0026ndash;47.2% [21; 23]. Komotar \u003cem\u003eet al.\u003c/em\u003e (2012) demonstrated significantly higher GTR rates for EETS (47.2%) compared to transcranial surgery (9.6%) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Nonetheless, craniotomy may be necessary in cases of poor sphenoid sinus pneumatization, vascular anomalies, lateral or posterior tumor extension, or fibrous consistency [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Craniotomy can also offer benefits in selected Knosp grade IV cases. Guan \u003cem\u003eet al\u003c/em\u003e. (2022) reported a 26.2% GTR rate in Knosp grade IV tumors treated via transcranial surgery [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVarious factors affect the extent of resection (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). One of the most important among them is Knosp scale grade [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In our series, GTR was achieved in twice as many patients with Knosp grade II tumors compared to grade III, and only 1% of grade IV tumors achieved GTR. These findings support previous reports indicating significantly higher GTR rates in Knosp grades 0\u0026ndash;II than in III\u0026ndash;IV [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Gondim \u003cem\u003eet al.\u003c/em\u003e (2014) similarly observed that Knosp grades III and IV were more frequently associated with STR [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. While we did not distinguish between grades IIIA and IIIB, prior studies show that GTR is more feasible in IIIA tumors [27; 28]. Grade IV tumors, due to cavernous sinus invasion, are particularly difficult to fully resect [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eA summary of studies with GPAs treated by EETS showing factors limiting extent of resection\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFactors limiting extent of resection\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYang \u003cem\u003eet al\u003c/em\u003e., 2024 [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Tumor volume\u003c/p\u003e\u003cp\u003e2. Maximum diameter\u003c/p\u003e\u003cp\u003e3. Multilobulated shape\u003c/p\u003e\u003cp\u003e4. Cavernous sinus invasion\u003c/p\u003e\u003cp\u003e5. Extension of the tumor to posterior fossa\u003c/p\u003e\u003cp\u003e6. Extent of suprasellar lateral extension\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChen \u003cem\u003eet al\u003c/em\u003e., 2022 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Maximum diameter\u003c/p\u003e\u003cp\u003e2. Knosp grade\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatel \u003cem\u003eet al\u003c/em\u003e., 2022 [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Preoperative tumor volume\u003c/p\u003e\u003cp\u003e2. Knosp grade\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCeylan \u003cem\u003eet al\u003c/em\u003e., 2021 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Suprasellar part of the tumor exceeding 2 cm in height\u003c/p\u003e\u003cp\u003e2. Cavernous sinus invasion\u003c/p\u003e\u003cp\u003e3. Extension of the tumor to anterior fossa, posterior fossa, and inferior wall of the lateral ventricle\u003c/p\u003e\u003cp\u003e4. Multilobulated shape\u003c/p\u003e\u003cp\u003e5. x/y ratio exceeding 1.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChibbaro \u003cem\u003eet al\u003c/em\u003e., 2021 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Cavernous sinus invasion\u003c/p\u003e\u003cp\u003e2. Suprasellar part of the tumor exceeding 2.5 cm in height\u003c/p\u003e\u003cp\u003e3. Fibrous consistence\u003c/p\u003e\u003cp\u003e4. Maximum diameter\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeto \u003cem\u003eet al\u003c/em\u003e., 2020 [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Extent of anteroposterior and retrosellar extension\u003c/p\u003e\u003cp\u003e2. High Zurich score\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGondim \u003cem\u003eet al\u003c/em\u003e., 2013 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Cavernous sinus invasion\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKoutourousiou \u003cem\u003eet al\u003c/em\u003e., 2013 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Multilobulated shape\u003c/p\u003e\u003cp\u003e2. Extension of the tumor in the coronal plane\u003c/p\u003e\u003cp\u003e3. Knosp grade IV\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDe Paiva Neto \u003cem\u003eet al.\u003c/em\u003e, 2010 [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Cavernous sinus invasion\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBeyond Knosp grade, cavernous sinus invasion itself is a major limiting factor for resection [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. De Paiva Neto \u003cem\u003eet al.\u003c/em\u003e (2010) reported GTR rates of 90% in non-invasive tumors but only 9.6% in invasive ones [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Tumors with cavernous sinus invasion also tend to be larger [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Extended EETS, including posterior ethmoidectomy, may enhance exposure and facilitate resection in such cases [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Although cavernous sinus invasion often limits GTR, Koutourousiou \u003cem\u003eet al.\u003c/em\u003e (2013) found that tumor shape and middle fossa extension \u0026mdash; rather than size or invasion \u0026mdash; were more predictive of incomplete resection [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Other anatomical predictors include suprasellar anteroposterior distance, retrosellar extension, and higher Zurich scores [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. GPA resection is also complicated by tumor consistency and capsular anatomy. Most PAs are soft, but 5\u0026ndash;13% can be fibrous [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Fibrous tumors are linked to higher rates of STR and increased surgical risk [27; 34]. In our cohort, 11.9% of tumors were fibrous \u0026mdash;comparable to prior reports \u0026mdash; but we did not observe a correlation between consistency and extent of resection. This may be due to our routine use of extracapsular dissection and extended approaches. The capsule is composed of peritumoral cells, microvascular structures and reticulin [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Capsule enclosing GPAs is often thicker than capsule enclosing smaller tumors, due to greater compression exerted by the tumor [9; 35]. However, capsule removal may be avoided to prevent cerebrospinal fluid (CSF) leakage [9; 35]. Another structure delineating the tumor from healthy tissues called pseudocapsule is composed of compressed reticulin and located between the tumor and pituitary gland [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Pseudocapsule can guide safe dissection, but its disruption may hinder complete resection [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVarious studies confirmed multilobulated shapes of GPAs negatively impact the extent of resection [9; 23; 37]. Such growth pattern becomes more evident with increasing vertical suprasellar expansion and may prevent descending of the suprasellar part [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Multilobulated shape might also suggest perforation of sellar diaphragm or subarachnoid invasion [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe extent of resection is also affected by the neurosurgeon\u0026rsquo;s level of experience, which typically improves with progression along the learning curve [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Our data suggest that surgical experience improves resection rates over time, with GTR/NTR achieved in more than half of cases after 2016, compared to less than one-third in the earliest time period. This is consistent with prior reports [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] highlighting the influence of the learning curve in endoscopic pituitary surgery. The rising incidence of postoperative DI in later years likely reflects a more aggressive approach affecting the hypothalamo-hypophyseal tract. However, the rate of permanent DI is still low (4.5%). We found that CSF leak and hemorrhagic complication rates declined over time, suggesting that the development of surgical skills was associated with improvements in both the extent of resection and overall safety. Surgical management of GPAs is associated with a higher complication rate compared to non-giant pituitary adenomas [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. EETS for GPAs carries a complication rate between 11.1% and 20.6% (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e) [17; 40], similar to that observed in smaller PitNETs (12.1\u0026ndash;19.3%) [41; 42]. Hypopituitarism is the most frequent complication, with incidence ranging from 13.7\u0026ndash;76.0% (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e) [11; 30]. In our cohort 22.2% of patients experienced new postoperative hypopituitarism. Recovery of pituitary function postoperatively is more common than new onset hypopituitarism [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The risk is influenced by tumor size, consistency, resection extent, and number of surgeries [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eA summary of studies with GPAs treated by EETS showing complications\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNew post-operative hypo\u003c/p\u003e\u003cp\u003epituita\u003c/p\u003e\u003cp\u003erism N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCSF leak N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerma\u003c/p\u003e\u003cp\u003enent DI N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMeningitis N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eICA injury N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHematoma N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eStroke N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eWorsening of vision N, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDeath N, (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCeylan\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2022\u003c/b\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e205\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (22.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (3.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e4 (2.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e3 (1.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChibbaro\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2021\u003c/b\u003e [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 (2.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMicko\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2022\u003c/b\u003e [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (17.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e2 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eElshazly\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2018\u003c/b\u003e [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (14.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eKoutourousiou\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2013\u003c/b\u003e [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (108 cavernous sinuses)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (9.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (5.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e2 (3.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDe Paiva Neto\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2010\u003c/b\u003e [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (13.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (9.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGondim\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e., \u003cb\u003e2014\u003c/b\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (36.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (8.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1 (2.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e2 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRahimli\u003c/b\u003e \u003cb\u003eet al\u003c/b\u003e.,\u003c/p\u003e\u003cp\u003e\u003cb\u003e2021\u003c/b\u003e [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (11.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (2.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 (4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e2 (4.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOur study\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28/126 22.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (2.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 (2.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12 (6.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 (2.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e7 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e4 (2.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eDI, often transient, is another notable complication, with permanent DI reported in up to 10% of cases [11; 14]. DI following EETS is neurogenic and results from hypothalamic or infundibular injury and impaired vasopressin transport [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In our cohort 20.5% of the patients had transient DI which became permanent in 4.5%. Transient DI was the most common complication in our patients. Another important complication of GPAs includes postoperative CSF leaks. Postoperative CSF leaks occur in 1.8\u0026ndash;16.7% of patients operated for GPAs [10; 23], with risk factors including lobular tumor shape, thin arachnoid-only diaphragmatic roof, high BMI, prior surgeries, and intraoperative CSF leak [\u003cspan additionalcitationids=\"CR47\" citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] Capsule preservation may reduce CSF leak risk [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePostoperative sellar hematoma is a rare complication of EETS for pituitary adenomas occurring in 1.5% of patients [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Significant risk factors include tumor diameter\u0026thinsp;\u0026ge;\u0026thinsp;30mm, suprasellar extension, tumor volume, cavernous sinus invasion, gonadotroph type of the tumor, use of antiplatelet drugs, and elevated body mass index [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. In tumors with transdiaphragmatic extensions the risk of a postoperative hematoma is also increased [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Such tumors may not be well encapsulated with small perforating arteries running along the pseudocapsule [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. We observed a relatively high rate of postoperative hematomas requiring treatment in our cohort (6.8%), surgical evacuation was necessary in 7 patients (4.0%). The rate of hematomas decreased after we started to perform extended EETS approaches routinely.\u003c/p\u003e\u003cp\u003eRhinologic complications are rare after EETS, but hyposmia can occur, especially with excessive coagulation of the superior and middle turbinates [41; 50]. We observed two such cases in our series.\u003c/p\u003e\u003cp\u003ePitNETs morphology and anatomical relationships are described using various grading systems proposed by Hardy \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], Wilson \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e], Knosp \u003cem\u003eet al.\u003c/em\u003e (Knosp scales) [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e], Goel \u003cem\u003eet al.\u003c/em\u003e (Giant tumors grading) [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e], Edal \u003cem\u003eet al.\u003c/em\u003e (SIPAP classification) [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], among others. In 2013 Trouillas \u003cem\u003eet al.\u003c/em\u003e proposed another grading scale - a five-tiered prognostic clinicopathological classification of PitNETs (Lyon\u0026rsquo;s clinicopathologic classification), which predicts the probability of tumor progression and the likelihood of achieving complete remission [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This classification offers improved prognostication over the WHO system by incorporating proliferation indices and invasiveness [16; 55]. In our series, patients with grade 2b tumors had worse outcomes, consistent with original findings, though the overall recurrence risk was lower compared to other studies. The most recent classification of PitNETs was proposed in 2024 by Ho \u003cem\u003eet al.\u003c/em\u003e, and assesses the disease severity, prognosis, and effects of therapy [56; 57].\u003c/p\u003e\u003cp\u003eThere are several limitations to this study. First, it is a retrospective analysis with some patients lost to follow-up. Second, the definition of GPAs is arbitrary and depends on the tumor\u0026rsquo;s maximum diameter, which may be prone to measurement error and introduce selection bias. Finally, the patients were treated over an extended time period, during which the surgeon\u0026rsquo;s growing experience and learning curve may have influenced the outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOverall, our findings confirm that EETS is a safe and effective treatment for GPAs, achieving satisfactory resection rates in most patients. Despite anatomical challenges and a moderate risk of complications, EETS enables durable control of tumor growth with acceptable morbidity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors declare no conflicts of interests. No funding was received for conducting this study. All patients gave informed consent for using their data in this study. The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Maria Sklodowska-Curie Institute\u0026mdash;Oncology Center in Warsaw, Poland (approval decision 86/2022).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConcept \u0026amp; Design: JK, BB; Literature Search: JK, BB; Data Extraction: BB, JK, MM; Statistical Analysis: BB, SB; Interpretation of Data: JK, BB, MM, SB; Drafting of Manuscript: BB, JK; Critical Revision: JK, MM, TM; Supervision: JK; Project Administration: TM\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript or supplementary information files, raw data in excel files can be uploaded on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSivakumar, W., Chamoun, R., Nguyen, V., \u0026amp; Couldwell, W. T. (2011). 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Outcomes and surgical nuances in management of giant pituitary adenomas: a review of 108 cases in the endoscopic era. \u003cem\u003eJ Neurosurg\u003c/em\u003e, 1-12. https://doi.org/10.3171/2021.10.Jns21659 \u003c/li\u003e\n\u003cli\u003eBerker, M., Hazer, D. B., Y\u0026uuml;cel, T., G\u0026uuml;rlek, A., Cila, A., Aldur, M., \u0026amp; Onerci, M. (2012). Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature. \u003cem\u003ePituitary\u003c/em\u003e,\u003cem\u003e 15\u003c/em\u003e(3), 288-300. https://doi.org/10.1007/s11102-011-0368-2 \u003c/li\u003e\n\u003cli\u003eChen, J., Liu, H., Man, S., Liu, G., Li, Q., Zuo, Q., Huo, L., Li, W., \u0026amp; Deng, W. (2022). Endoscopic vs. Microscopic Transsphenoidal Surgery for the Treatment of Pituitary Adenoma: A Meta-Analysis [Systematic Review]. \u003cem\u003eFrontiers in Surgery\u003c/em\u003e,\u003cem\u003e 8\u003c/em\u003e. https://doi.org/10.3389/fsurg.2021.806855 \u003c/li\u003e\n\u003cli\u003eMavromati, M., Mavrakanas, T., Jornayvaz, F. R., Schaller, K., Fitsiori, A., Vargas, M. I., Lobrinus, J. A., Merkler, D., Egervari, K., Philippe, J., Leboulleux, S., \u0026amp; Momjian, S. (2023). The impact of transsphenoidal surgery on pituitary function in patients with non-functioning macroadenomas. \u003cem\u003eEndocrine\u003c/em\u003e,\u003cem\u003e 81\u003c/em\u003e(2), 340-348. https://doi.org/10.1007/s12020-023-03400-z \u003c/li\u003e\n\u003cli\u003ePrete, A., Corsello, S. M., \u0026amp; Salvatori, R. (2017). 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F., \u0026amp; Basso, A. (2019). Anatomical Risk Factors for Intraoperative Cerebrospinal Fluid Leaks During Transsphenoidal Surgery for Pituitary Adenomas. \u003cem\u003eWorld Neurosurg\u003c/em\u003e,\u003cem\u003e 124\u003c/em\u003e, e346-e355. https://doi.org/10.1016/j.wneu.2018.12.094 \u003c/li\u003e\n\u003cli\u003eXue, H., Wang, X., Yang, Z., Bi, Z., \u0026amp; Liu, P. (2020). Risk factors and outcomes of cerebrospinal fluid leak related to endoscopic pituitary adenoma surgery. \u003cem\u003eBr J Neurosurg\u003c/em\u003e,\u003cem\u003e 34\u003c/em\u003e(4), 447-452. https://doi.org/10.1080/02688697.2020.1754336 \u003c/li\u003e\n\u003cli\u003eYounus, I., Gerges, M. M., Godil, S. S., Uribe-Cardenas, R., Dobri, G. A., Ramakrishna, R., \u0026amp; Schwartz, T. H. (2020). Incidence and risk factors associated with reoperation for sellar hematoma following endoscopic transsphenoidal pituitary surgery. \u003cem\u003eJ Neurosurg\u003c/em\u003e,\u003cem\u003e 133\u003c/em\u003e(3), 702-708. https://doi.org/10.3171/2019.6.Jns191169 \u003c/li\u003e\n\u003cli\u003eGstrein, N. A., Zwicky, S., Serra, C., Hugelshofer, M., Regli, L., Soyka, M. B., Holzmann, D., \u0026amp; Meerwein, C. M. (2023). Rhinologic outcome of endoscopic transnasal-transsphenoidal pituitary surgery: an institutional series, systematic review, and meta-analysis. \u003cem\u003eEur Arch Otorhinolaryngol\u003c/em\u003e,\u003cem\u003e 280\u003c/em\u003e(9), 4091-4099. https://doi.org/10.1007/s00405-023-07934-w \u003c/li\u003e\n\u003cli\u003eWilson, C., Tyrell, J., \u0026amp; Fitzgerald, P. (1979). Clinical management of pituitary disorders. \u003cem\u003eNeurosurgical management of large and invasive pituitary tumors. Tindall GT, Collins WF (ed): Raven Press, New York\u003c/em\u003e, 335-342. \u003c/li\u003e\n\u003cli\u003eKnosp, E., Steiner, E., Kitz, K., \u0026amp; Matula, C. (1993). Pituitary Adenomas with Invasion of the Cavernous Sinus Space: A Magnetic Resonance Imaging Classification Compared with Surgical Findings. \u003cem\u003eNeurosurgery\u003c/em\u003e,\u003cem\u003e 33\u003c/em\u003e(4), 610-618. https://journals.lww.com/neurosurgery/fulltext/1993/10000/pituitary_adenomas_with_invasion_of_the_cavernous.8.aspx \u003c/li\u003e\n\u003cli\u003eGoel, A., Nadkarni, T., Muzumdar, D., Desai, K., Phalke, U., \u0026amp; Sharma, P. (2004). Giant pituitary tumors: a study based on surgical treatment of 118 cases. \u003cem\u003eSurg Neurol\u003c/em\u003e,\u003cem\u003e 61\u003c/em\u003e(5), 436-445; discussion 445-436. https://doi.org/10.1016/j.surneu.2003.08.036 \u003c/li\u003e\n\u003cli\u003eEdal, A. L., Skj\u0026ouml;dt, K., \u0026amp; Nepper-Rasmussen, H. J. (1997). SIPAP--a new MR classification for pituitary adenomas. Suprasellar, infrasellar, parasellar, anterior and posterior. \u003cem\u003eActa Radiol\u003c/em\u003e,\u003cem\u003e 38\u003c/em\u003e(1), 30-36. https://doi.org/10.1080/02841859709171238 \u003c/li\u003e\n\u003cli\u003eTrouillas, J., Jaffrain-Rea, M. L., Vasiljevic, A., Raverot, G., Roncaroli, F., \u0026amp; Villa, C. (2020). How to Classify the Pituitary Neuroendocrine Tumors (PitNET)s in 2020. \u003cem\u003eCancers (Basel)\u003c/em\u003e,\u003cem\u003e 12\u003c/em\u003e(2). https://doi.org/10.3390/cancers12020514 \u003c/li\u003e\n\u003cli\u003eHo, K. K. Y., Fleseriu, M., Wass, J., Katznelson, L., Raverot, G., Little, A. S., Casta\u0026ntilde;o, J. P., Reincke, M., Lopes, M. B., Kaiser, U. B., Chanson, P., Gadelha, M., \u0026amp; Melmed, S. (2024). A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis. \u003cem\u003eLancet Diabetes Endocrinol\u003c/em\u003e,\u003cem\u003e 12\u003c/em\u003e(3), 209-214. https://doi.org/10.1016/s2213-8587(23)00382-0 \u003c/li\u003e\n\u003cli\u003eFookeerah, P., Varikatt, W., Shingde, M., Dexter, M. A. J., Lau, S. L., McCormack, A., \u0026amp; McLean, M. (2025). Assessing the clinical application of the PANOMEN 3 classification in a large cohort of pituitary tumors. \u003cem\u003eEur J Endocrinol\u003c/em\u003e,\u003cem\u003e 193\u003c/em\u003e(1), 56-64. https://doi.org/10.1093/ejendo/lvaf122 \u003c/li\u003e\n\u003cli\u003eRahimli, T., Hidayetov, T., Yusifli, Z., Memmedzade, H., Rajabov, T., \u0026amp; Aghayev, K. (2021). Endoscopic Endonasal Approach to Giant Pituitary Adenomas: Surgical Outcomes and Review of the Literature. \u003cem\u003eWorld Neurosurgery\u003c/em\u003e,\u003cem\u003e 149\u003c/em\u003e, e1043-e1055. https://doi.org/https://doi.org/10.1016/j.wneu.2021.01.019 \u003c/li\u003e\n\u003cli\u003ePatel, B. K., Binu, A., Stanley, A., Shah, S. K., H, R. D., George, T., H, V. E., \u0026amp; Nair, P. (2022). Large Pituitary Adenoma: Strategies to Maximize Volumetric Resection Using Endoscopic Endonasal Approaches and an Analysis of Factors Limiting Resection. \u003cem\u003eWorld Neurosurg\u003c/em\u003e,\u003cem\u003e 167\u003c/em\u003e, e694-e704. https://doi.org/10.1016/j.wneu.2022.08.070\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pituitary","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pitu","sideBox":"Learn more about [Pituitary]()","snPcode":"11102","submissionUrl":"https://submission.nature.com/new-submission/11102/3","title":"Pituitary","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"giant pituitary adenomas, endoscopic endonasal approach","lastPublishedDoi":"10.21203/rs.3.rs-7557934/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7557934/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThe giant pituitary adenomas (GPAs) are still a challenging surgical problem. They comprise 10\u0026ndash;15% of operated pituitary adenomas. The advances of endoscopic techniques allow the resection of pituitary tumors previously operated by transcranial approaches. The aim of the study was to review the surgical results in a series of patients with GPAs (diameter\u0026thinsp;\u0026ge;\u0026thinsp;40 mm) operated with endoscopic endonasal approach.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe study is a retrospective analysis of a series of 176 patients (66 women and 110 men) treated from the 2007 to 2023 by the endoscopic transsphenoidal surgeries for GPAs (\u0026gt;\u0026thinsp;40mm). The mean age of the patients was 57.0 years (20\u0026ndash;81 years), and the mean follow-up period was 7.5 years (0\u0026ndash;16 years). Forty patients had 1a grade of the Lyon\u0026rsquo;s clinicopathologic classification, 7 patients \u0026ndash; 1b, 111 patients \u0026ndash; 2a, and 18 patients \u0026ndash; 2b.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe gross total resection was accomplished in 73 cases (41.5%). Extended endoscopic approaches were used in 11 patients (6.3%). The mortality rate was 2.3%. Postoperatively 60% of the patients showed varying improvement in visual field defects and visual acuity. The morbidity rate was 33.5%. During a mean 7.5 years follow-up there were 29 (15.9%) cases of recurrences.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eOur results indicate that resection with endoscopic endonasal approach can be a safe and effective method for the treatment of patients with GPAs. It is the alternative for transcranial approaches.\u003c/p\u003e","manuscriptTitle":"Endoscopic endonasal resection of giant pituitary neuroendocrine tumors - case series from the referral pituitary center","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-17 08:35:36","doi":"10.21203/rs.3.rs-7557934/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-17T14:28:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-17T14:14:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-14T13:14:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"281280737670664358504342928381645322750","date":"2025-09-09T12:43:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"101188203322830876833181007859798673061","date":"2025-09-09T08:50:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261125728090665902918238821799414348083","date":"2025-09-09T07:20:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-09T07:13:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-08T04:31:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-08T04:30:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pituitary","date":"2025-09-07T17:45:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pituitary","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pitu","sideBox":"Learn more about [Pituitary]()","snPcode":"11102","submissionUrl":"https://submission.nature.com/new-submission/11102/3","title":"Pituitary","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3bf4278d-2817-4f1d-9000-2ab6743cc029","owner":[],"postedDate":"September 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:07:05+00:00","versionOfRecord":{"articleIdentity":"rs-7557934","link":"https://doi.org/10.1007/s11102-025-01596-z","journal":{"identity":"pituitary","isVorOnly":false,"title":"Pituitary"},"publishedOn":"2025-11-02 15:57:54","publishedOnDateReadable":"November 2nd, 2025"},"versionCreatedAt":"2025-09-17 08:35:36","video":"","vorDoi":"10.1007/s11102-025-01596-z","vorDoiUrl":"https://doi.org/10.1007/s11102-025-01596-z","workflowStages":[]},"version":"v1","identity":"rs-7557934","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7557934","identity":"rs-7557934","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}