Comparison of the lumbar drain and the hydroxyapatite methods for cerebrospinal fluid leakage after endoscopic skull base surgery

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We enrolled 211 consecutive patients with grade 2 or 3 CSF leakage after EEA. The most common preoperative diagnoses were pituitary adenoma (n=62, 29%), meningioma (n=50, 24%), and craniopharyngioma (n=28, 13%). Vascularized nasoseptal flaps were used in most cases (98%). We used the L-method and H-method in 83 (39%) and 103 patients (49%), respectively. The overall reconstruction-related complication and CSF leakage rates were 8% (18/211) and 6% (12/211), respectively. The complications included CSF leakage (n=12), infection (n=4), postoperative compression (n=2), and brain herniation (n=1). The complication and CSF leakage rates did not differ significantly between the L-method (12% and 10%, respectively) and H-method (8% and 4%, respectively) ( P =0.326 and 0.112, respectively). All infections occurred in the H-method ( P =0.070). Postoperative hospital stay was significantly shorter with the H-method (6.9 days) compared to the L-method (10.0 days) ( p <0.001). Skull base reconstruction using hydroxyapatite effectively prevented CSF leakage and ensured patient comfort and shorter hospitalization without postoperative lumbar drainage, although postoperative infection requires consideration. Biological sciences/Neuroscience Biological sciences/Neuroscience/Diseases of the nervous system Biological sciences/Neuroscience/Diseases of the nervous system/Cancer in the nervous system Health sciences/Oncology/Surgical oncology expanded endoscopic surgery skull base reconstruction hydroxyapatite lumbar drainage infection Figures Figure 1 Figure 2 Figure 3 Introduction Recently, endoscopic approaches via the nasal cavity have garnered interest for the removal of tumors in the skull base region, including pituitary tumors. Notably, the expanded endoscopic approach (EEA) has enabled nasal access for the treatment of tumors such as giant pituitary adenomas, meningiomas, and craniopharyngiomas, which previously required craniotomy and traditional skull base approaches. 1–4 The nasoseptal mucosal flap graft, which is pedicled from the septal branch of sphenopalatine artery, has facilitated expanded endoscopic skull base surgeries without cerebrospinal fluid (CSF) leakage. 5,6 During trans-sphenoidal surgery for pituitary tumors, traditional reconstruction methods entailed abdominal fat grafting and postoperative lumbar drainage (L-drainage) to manage CSF leakage. 5,7,8 Recent efforts have explored alternative reconstruction techniques, including nasoseptal flap grafts, fascia lata grafts, artificial dural grafts, coagulation component patches such as TachoSil®, and even methods utilizing artificial bone materials such as hydroxyapatite cement (HydroSet®) aimed at preventing CSF leakage. 9–13 However, the most efficient and optimal method is under debate. In this study, we analyzed the outcomes of skull base reconstruction procedures performed at our institution to address CSF leakage during recent EEA. We compared two frequently employed techniques, viz. the insertion of postoperative L-drainage (L-method) and the use of injectable hydroxyapatite cement (HydroSet®) without L-drainage (H-method). The study aimed to conduct a comparative analysis of the efficacy, risks, and adverse effects of these two methods, contributing to the ongoing discourse on the most effective and optimal approach. Methods Study Cohort This study was a retrospective review of a case series of a total of 768 patients who underwent endoscopic skull base surgery through the nasal cavity at our institution between 2016 and 2023. All available clinical information and neuroimaging data were collected the approval of our institutional review board. This study has been performed in accordance with the Declaration of Helskinki and the informed consent was obtained from all participants. The inclusion criteria for this study were as follows: ( 1 ) patients who underwent expanded endoscopic skull base surgery, ( 2 ) grade 2 or 3 CSF leakage, ( 3 ) reconstruction was performed solely through the endoscopic intranasal approach, and ( 4 ) availability of complete clinical data before and after surgery. CSF leakage was graded based on Kelly’s classification. Grade 2 CSF leakage involves a moderate leak with a defect in the sellar diaphragm, whereas grade 3 includes a significant defect in the sellar diaphragm with a substantial amount of CSF leakage. 14 Patients who underwent surgery for pituitary tumors using the non-expanded trans-sphenoidal approach (n = 448), those who did not experience grade 2 or 3 CSF leakage after expanded endoscopic skull base surgery (n = 94), those who underwent skull base reconstruction through craniotomy (n = 1), and patients with incomplete clinical data (n = 14) were excluded from the study. Consequently, the study included 211 patients. Demographic Data Of the 211 patients, 85 (40%) were men and 126 (60%) were women, with a median age of 55 years (range, 19–74 years). The preoperative diagnoses were as follows: pituitary tumor (n = 62, 29%), meningioma (n = 50, 24%), craniopharyngioma (n = 28, 13%), Rathke’s cleft cyst (n = 17, 8%), sinonasal malignancy (n = 16, 8%), chordoma or chondrosarcoma (n = 8, 4%), and CSF leakage (n = 22, 10%). The most common preoperative symptoms included visual disturbance (55%), headaches (19%), and sinonasal symptoms such as rhinorrhea, nasal congestion, and epistaxis (12%). The median tumor size was 2.8 cm (range, 0.5–6.0 cm). The demographic and clinical data of the 211 patients are summarized in Table 1 . Table 1 Demographical and clinical data of enrolled patients (n = 211) Category Value (range or %) No of patients 211 Median age (range; years) 55 (19–74) Sex Male Female 85 (40%) 126 (60%) Body mass index (kg/m 2 ) Median value (range) 25.4 (17.1–37.6) Past medical & social history Hypertension Diabetes mellitus Smoking Drinking alcohol 65 (31%) 30 (14%) 47 (22%) 81 (38%) Initial symptoms & signs Visual disturbance Headache Sinonasal symptoms Dizziness Hormonal imbanlance Neurological deterioration Cognitive dysfunction No symptoms & signs 117 (55%) 40 (19%) 25 (12%) 11 (5%) 9 (4%) 8 (4%) 6 (3%) 29 (14%) Preoperative diagnosis Pituitary adenoma Meningioma Craniopharyngioma Rathke’s cleft cyst Sinonasal malignancy Chordoma or Chondrosarcoma Cerebrospinal fluid leakage Others 62 (29%) 50 (24%) 28 (13%) 17 (8%) 16 (8%) 8 (4%) 22 (10%) 8 (4%) Maximal diameter of tumors (cm) Median value (range) 2.8 (0.5–6.0) * No, number; Skull Base Reconstruction Methods In cases where a significant dead space remained after tumor resection with EEA, the space was filled using either Gelfoam® (Pfizer, New York, NY, USA) sponge or autologous abdominal fat graft (Fig. 1 a). If a hole was created to the extent that restoration to the diaphragm sellae was feasible, it was patched using TachoSil® (Baxter, Deerfield, Illinois, USA) patch and the pituitary cavity was filled with Gelfoam® sponge. Deficient dura mater was reconstructed using an artificial dura mater substitute known as Duragen® (Integra, Princeton, NJ, USA) or autologous fascia lata graft. The latter was performed by creating a 5–10-cm incision in the patient’s right thigh to obtain a direct graft or with a commercially available cadaveric fascia lata graft. When grafting the fascia lata, a double-layered construct consisting of an inlay and onlay was fabricated to minimize CSF leakage using the button-hole method (Fig. 1 b). The skull base defect was also repaired using an autologous bone graft harvested from the nasal septum or anterior wall of the sphenoid sinus. When the bones around the surgical defect were intact and well exposed without damage, and when there width the nasoseptal vascularized mucosal graft was sufficient with a low risk of postoperative infection, HydroSet® (Stryker, Kalamazoo, MI, USA), i.e., injectable hydroxyapatite cement, was used. The use of HydroSet® facilitated solid reconstruction with an artificial bone material, while simultaneously preventing CSF leakage (Fig. 1 c). Additionally, the entire HydroSet® surface was covered with the previously harvested nasoseptal flap to prevent exposure within the nasal cavity (Fig. 1 d). In all cases where HydroSet® was not used, reconstruction of the skull base mucosa was achieved by covering it with the nasoseptal flap. To allow adhesion between each reconstructed layer, a minimum of 48 hours was required after surgery. Therefore, postoperative L-drainage was performed for CSF drainage via a spinal tap. Patients were typically restricted to minimal walking for an average of 5 days, and CSF was drained through the L-drain before removal, ensuring that no CSF leakage occurred at the surgical site, which was confirmed by examination by an otolaryngologist. Study Design Postoperative L-drainage was performed in 83 (39%) of 211 patients, whereas HydroSet® was used without L-drainage in 103 patients (49%). No patient underwent L-drainage and HydroSet® reconstruction simultaneously. The technique of inserting the L-drain postoperatively was designated as the “L-method” (Fig. 2 a), whereas the method of reconstruction using HydroSet® was designated as the “H-method” (Fig. 2 b) and the two methods were compared. The preoperative diagnosis distribution, tumor size, surgical approach, operative time, extent of removal, method of reconstruction, occurrence of complications associated with reconstruction, frequency of postoperative CSF leakage, and length of hospital stay were compared. Statistical Analysis Student’s t-test was utilized for the comparison of continuous variables between the two groups, whereas Fisher's exact test and Pearson chi-square test were employed for categorical variables. The preoperative diagnosis distribution, maximum tumor diameter, distribution of endoscopic approach, need for reoperation, surgical time, extent of CSF leakage, extent of tumor removal, frequency of abdominal and fascia lata grafting, number of reconstruction layers, frequency of complications related to reconstruction, frequency of postoperative CSF leakage, length of hospital stay, and other variables were compared between the two reconstruction methods. All statistical analyses were conducted using IBM SPSS Statistics program version 21.0 (IBM Corp., Armonk, NY, USA). The p -values < 0.05 were considered statistically significant. Results Overall Surgical Results and Reconstruction-Related Complications The most common approach was the trans-tubercular approach, which was performed in 159 (75%) of 211 patients, followed by the trans-sellar approach (n = 24, 11%), trans-cribriform approach (n = 14, 7%), trans-clival approach (n = 10, 5%), and trans-pterygopalatine fossa approach (n = 1, 2%). Fifty-six (27%) surgeries were reoperations due to tumor recurrence or CSF leakage. The median surgical duration was 250 min (range, 23–783 min). Grade 2 CSF leakage occurred in 35 patients (17%), whereas grade 3 leakage occurred in 176 patients (83%). Nasoseptal mucosal grafts were used in almost all cases (n = 207, 98%). Turbinate mucosal flap grafting was performed in 3 patients (1%) and vascular-pedicled muscle free grafting was employed in 1 patient (0.5%). Autologous abdominal fat grafting was performed in 26 patients (12%), whereas fascia lata grafting was performed in 41 patients (19%). Autologous grafting was used in 15 (7%) of 41 patients, and cadaveric fascia lata was used in 26 patients (12%). As mentioned earlier, HydroSet® was used in 103 patients (49%), and postoperative L-drainage in 83 patients (39%). Drainage was conducted for an average of 5 days (median, range: 2–8 days), with an average of 150 mL of fluid (median, range: 100–240 mL) drained per day. Neither postoperative L-drainage nor HydroSet® was used in 25 patients (12%). Grade 2 CSF leakage occurred after surgery for large pituitary tumors in 21 patients and grade 3 in 2 patients. The leakage site was sealed with a TachoSil® patch, and reconstruction was performed using Duragen®, bone grafting, and nasoseptal flap grafting. In one case, after treating a chordoma using the trans-clival approach, the CSF leakage site was sealed using a TachoSil® patch, and the nasoseptal flap was employed for reconstruction. In another case, where CSF leakage occurred after surgery for a pituitary tumor, the L-drain was not inserted due to the presence of spontaneous subarachnoid hemorrhage before and after surgery. Instead, reconstruction was instituted using abdominal fat grafting, fascia lata grafting, and a nasoseptal flap. In all 25 cases, there were no complications such as postoperative CSF leakage. The tumor was completely or almost completely excised in 165 patients (87%). Complications related to reconstruction occurred in 18 patients (8%). Postoperative CSF leakage occurred in 12 patients (6%), and infection occurred in 4 patients (2%). One patient (0.5%) who developed septicemia occurred due to ventriculitis failed to regain consciousness, falling into a vegetative state, and was only capable of spontaneous breathing with the eyes open (Fig. 3 ). The overall surgical outcomes and complications of the 211 patients are summarized in Table 2 . Table 2 Surgical results of enrolled patients (n = 211) Category Value Approach Trans-sellar Trans-tubercular/planum Trans-cribriform Trans-clival Trans-cavernous Trans-PPF 24 (11%) 159 (75%) 14 (7%) 10 (5%) 3 (1%) 1 (1%) Revision operation 56 (27%) Operation time (min) 250 (23–783) * Grade of CSF leakage Grade 2 Grade 3 35 (17%) 176 (83%) Pedicled mucosal flap Nasoseptal flap Turbinate flap Others 207 (98%) 3 (1%) 1 (1%) Abdominal fat graft 26 (12%) Fascia lata graft Autologous Cadaveric Acellular dermal matrix 15 (7%) 26 (12%) 135 (64%) Autologous bone graft 43 (20%) Hydroxyapatite 103 (49%) Postop L-drainage 83 (39%) Duration of L-drainage (days) 5 ( 2 – 8 ) * Amount of daily drainage (mL) 150 (100–240) * Extent of removal Gross total removal Near total removal Subtotal removal Partial removal 131 (69%) 34 (18%) 19 (10%) 5 (3%) Reconstruction-related Cx 18 (8%) Postoperative CSF leakage 12 (6%) Postoperative infection Postoperative compression Brain herniation 4 (2%) 2 (1%) 1 (1%) Postoperative hospital stay (days) 7 (3–38) * * Median value (range); PPF, pterygopalatine fossa; CSF, cerebrospinal fluid; L-drainage, lumbar drainage; Cx, complications Comparison of Surgical Outcomes between the L- and H-Methods There were no differences in the distribution of age, sex, and obesity between the two methods. Among patients who underwent the L-method, the most common diagnosis was pituitary adenoma (n = 25, 30%), followed by CSF leakage (n = 16, 19%), malignant tumor in the nasal cavity (n = 14, 17%), Rathke's cleft cyst (n = 7, 8%), craniopharyngioma (n = 6, 7%), meningioma (n = 5, 6%), and chordoma or chondrosarcoma (n = 3, 4%). In contrast, meningiomas, particularly tuberculum sellae meningiomas, were the most common diagnoses among patients who underwent the H-method, occurring in 45 patients (44%), followed by craniopharyngiomas in 22 patients (22%), pituitary adenomas in 15 patients (15%), Rathke's cleft cysts in 10 patients (10%), and other tumors in 6 patients (6%), showing a significant difference compared to the distribution of patients who underwent reconstruction with the L-method ( p < 0.001). The mean maximum diameter (3.0 ± 1.2 cm) in patients who underwent L-drainage was significantly larger than that (2.4 ± 0.9cm) in patients treated with the H-method ( p < 0.001). In the L-method group, the trans-tubercular approach was used in 45 patients (58%), the trans-sellar approach in 15 patients (18%), and the trans-cribriform approach was employed in 13 patients (16%). In contrast, in the H-method group, the trans-tubercular approach was used in 95 patients (95%) ( p < 0.001). The frequency of reoperation was higher in the L-method with 36 patients (43%) compared to 13 patients (13%) in the H-method ( p < 0.001). Grade 3 CSF leakage occurred in 71 patients (86%) who underwent L-drainage, whereas it occurred in 101 patients (98%) who underwent the H-method ( p = 0.001). Abdominal fat grafting and autologous bone grafting were performed more frequently in the L-method in 23 (28%) and 26 patients (31%), respectively, compared to 2 patients each (2%) in the H-method (both p < 0.001). In the L-method group, fascia lata grafting was used in 26 patients (31%), including 15 autologous grafts (18%) and 11 cadaveric grafts (13%), which was significantly higher compared to only cadaveric graft in 13 patients (13%) in the H-method ( p < 0.003). The surgical outcomes and risks of the L- and H-methods are summarized and compiled in Table 3 . Table 3 Comparison between the lumbar drainage method (L-method) and the hydroxyapatite method (H-method) Category L-method H-method p value No of patients 83 103 Age (years) 53.1 ± 13.5 * 51.7 ± 12.1 * 0.461 Sex Male Female 36 (43%) 47 (57%) 36 (35%) 67 (65%) 0.241 Body mass index (kg/m 2 ) 25.3 ± 3.4 * 25.0 ± 3.6 * 0.587 Preoperative diagnosis Pituitary adenoma Meningioma Craniopharyngioma Sinonasal malignancy * Rathke’s cleft cyst Chordoma or Chondrosarcoma Cerebrospinal fluid leakage Others 25 (30%) 5 (6%) 6 (7%) 14 (17%) 7 (8%) 3 (4%) 16 (19%) 7 (8%) 15 (15%) 45 (44%) 22 (22%) 1 (1%) 10 (10%) 4 (4%) 5 (5%) 1 (1%) < 0.001 Maximal diameter of tumors 3.0 ± 1.2 * 2.4 ± 0.9 * < 0.001 Approach Trans-sellar Trans-tubercular/planum Trans-cribriform Trans-clival Trans-cavernous Trans-PPF 15 (18%) 45 (58%) 13 (16%) 5 (6%) 1 (1%) 1 (1%) 2 (2%) 95 (95%) 0 (0%) 3 (3%) 0 (0%) 0 (0%) < 0.001 Revision operation 36 (43%) 13 (13%) < 0.001 Operation time (min) 256 ± 154 * 285 ± 108 * 0.139 Grade of CSF leakage Grade 2 Grade 3 12 (14%) 71 (86%) 2 (2%) 101 (98%) 0.001 Abdominal fat graft 23 (28%) 2 (2%) < 0.001 Fascia lata graft Autologous Cadaveric Acellular dermal matrix 15 (18%) 11 (13%) 45 (54%) 0 (0%) 13 (13%) 74 (72%) < 0.001 0.013 Autologous bone graft 26 (31%) 2 (2%) < 0.001 Reconstruction-related Cx 10 (12%) 8 (8%) 0.326 Postoperative CSF leakage 8 (10%) 4 (4%) 0.112 Postoperative infection 0 (0%) 4 (4%) 0.070 Postoperative stay (days) 10.0 ± 6.3 * 6.9 ± 2.8 * < 0.001 * Mean value ± standard deviation; L-drainage, lumbar drainage; No, number; PPF, pterygopalatine fossa; CSF, cerebrospinal fluid; Cx, complications Comparison of Complications between the L- and H-Methods Complications related to reconstruction occurred in 10 patients (11%) in the L-method, compared to 8 patients (8%) in the H-method, but the difference lacked statistical significance ( p = 0.326). The 10 complications in the L-method included 8 cases (10%) of CSF leakage, 1 case of optic nerve compression by reconstruction materials, and 1 case of brain tissue herniation through the bone defect. The 8 complications in the H-method included 4 cases (4%) of CSF leakage and 4 cases (4%) of infection. Consequently, postoperative CSF leakage occurred in 10% (8/83) of cases in the L-method and 4% (4/103) of cases in the H-method, with no statistically significant difference ( p = 0.112). However, postoperative infection occurred only in the H-method group in 4 cases (4%) ( p = 0.070). Nonetheless, the length of hospital stay was significantly shorter with the H-method, at 6.9 ± 2.8 days, compared to 10.0 ± 6.3 days in the L-method ( p < 0.001). Discussion With the advent of endoscopic surgery for simple pituitary adenomas and tumors involving the entire skull base, the indications for expanded endoscopic skull base surgery have undergone gradual expansion. The increasing application of endoscopic surgery for skull base tumors is attributed to the development of effective techniques such as vascularized nasoseptal mucosal grafting, which provides adequate blood supply and effectively reconstructs the skull base region. This advancement has addressed one of the most challenging hurdles in skull base surgery, which is effectively preventing CSF leakage. 5,6 Nasoseptal mucosal flap grafting was used in 98% of patients in this study. Although there are drawbacks to the nasoseptal flap, such as nasal mucosa damage and olfactory dysfunction, these issues can be minimized by reducing the use of monopolar electrocautery and incising the mucosa with a knife or scissors. 15 Although the nasoseptal flap can significantly reduce CSF leakage, it takes time for the graft to adhere completely to the skull base bone or normal mucosa in the surgical area. The exact duration required for the graft to adhere sufficiently to effectively prevent CSF leakage has not been established, but it is known to take a minimum of 2 to 7 days. 5,6 If CSF leakage is not effectively prevented or diverted before the adherence of the nasoseptal flap, CSF leakage can occur despite the use of grafting. Therefore, traditionally, L-drainage was the most frequently used method to divert CSF for a certain period of time after surgery. 8 The use of the lumbar catheter to drain a certain amount of CSF per day can reduce intracranial pressure and pressure on the skull base region involved in surgery, thereby decreasing the risk of CSF leakage at the surgical site. Recent prospective studies have also demonstrated that L-drainage significantly reduces CSF leakage compared to non-use of this method. 8 However, inserting an L-drainage catheter for a certain period of time after surgery can make patients extremely uncomfortable and often necessitates bed rest, preventing them from engaging in any activity. Although rare, prolonged bed rest increases the risk of infections such as pneumonia and can lead to serious complications such as pulmonary thromboembolism and deep vein thrombosis. Moreover, prolonged drainage of large amounts of CSF carries the risk of serious complications such as subdural hemorrhage and downward herniation of the brain. Therefore, recent efforts have focused on avoiding the use of L-drainage whenever possible or minimizing the duration and amount of drainage if its use is necessary. Hydroxyapatite cement has been used as an artificial bone material for reconstructing defects after cranial surgery for quite some time. Hydroset® is a hydroxyapatite cement product that can be instilled using a syringe, making it suitable for use in the skull base region through the nasal cavity. Hydroset® consists of a powder form of hydroxyapatite mixed with a liquid adhesive, which hardens into a solid when exposed to moisture. Before hardening, it exists in a semi-solid state, allowing it to be shaped and molded in the desired form and quantity, achieving some degree of adhesion to the surrounding tissues. Consequently, some institutions initially proposed the potential use of Hydroset® as a reconstructive material following endoscopic skull base surgery. 9,10 If Hydroset® can effectively seal the skull base defect without the need for postoperative L-drainage and successfully address CSF leakage, it could indeed be considered as a new material for skull base reconstruction. According to early reports from some institutions, the use of Hydroset® may lead to delayed CSF leakage, and exposure of the material within the nasal cavity may cause various nasal problems such as recurrent crust formation. Additionally, as it is an artificial material (rather than an autologous graft), the possibility of serious infections must also be considered. Serious ventriculitis occurred in initially in cases of giant pituitary adenomas treated in our study. Therefore, despite its potential benefits, the use of Hydroset® as a reconstructive material warrants meticulous evaluation, given its potential complications. These issues can be overcome by covering the exposed area with a large nasoseptal flap after Hydroset® application and adequate administration of antibiotics postoperatively. Immediate CSF leakage after surgery can be prevented with Hydroset®, whereas delayed leakage can be averted by double sealing with the adhered nasoseptal flap. Multiple layers of reconstructive materials can effectively prevent CSF leakage. 7 In the event of grade 2 or 3 CSF leakage, postoperative infection is always a significant concern. Therefore, a triple antibiotic regimen consisting of vancomycin, third-generation cephalosporins, and metronidazole can effectively reduce the risk of postoperative infection. In our study, bacterial infections did not occur after the use of triple antibiotic therapy, and only one case of delayed aseptic meningitis was reported. Although rare, postoperative herniation of the brain through the defect site as well as nerve compression and injury are serious complications that can occur after endoscopic skull base surgery. Creating a solid reconstructive layer outside the surgical site using Hydroset® can help avert these complications. 9,10 Furthermore, the frequency of multi-layered reconstruction methods, such as abdominal fat grafting and autologous fascia lata grafting, was also reduced. Additionally, without the need for postoperative L-drainage, patients were able to resume movement sooner, thereby reducing the recovery period and effectively shortening hospital stay. Although the occurrence and probability of simple complications are important, patient satisfaction and quality of life after surgery are also crucial considerations. This study compared the most frequently used method of postoperative L-drainage with a newer reconstruction method using Hydroset®, from amongst the methods of defect repair after skull base expansion surgery, to compare the advantages and disadvantages of each method. However, this was not a randomized prospective study but a retrospective study, which could lead to bias in the selection and comparison of reconstruction methods. For example, in this study, the diseases and approaches targeted by the two methods did not show a uniform distribution. Therefore, randomized prospective studies are needed to conduct a more scientific comparison. Conclusion In the event of grade 2 or grade 3 CSF leakage after expanded endoscopic skull base surgery, using a postoperative L-drainage as well as injecting hydroxyapatite cement without L-drainage were effective in preventing CSF leakage after surgery. The method of using hydroxyapatite cement without an L-drainage catheter allows for the omission of L-drain insertion postoperatively and shortens the postoperative hospital stay. However, surgeons should be aware of the increased risk of postoperative infections associated with the use of hydroxyapatite cement without an L-drain and implement appropriate precautions. Declarations Acknowledgment No funding was received in support of this work, and no benefits in any form have been or will be received from a commercial party, directly or indirectly, related to the subject of this manuscript. The submitted manuscript does not contain information about any medical devices or drugs. Author contributions M.Y. and Y.-H.K. wrote the main manuscript text. All authors reviewed the manuscript. M.Y., G.J.K., J.J., Y.B., C.L. and Y.-H.K. prepared figures and tables. J.H.K., S.W.S., C.-K.H., J.H.K., Y.H.K. and D.-S.K. supported basic materials. C.-K.H., Y.H.K., D.-S.K. and Y.-H.K. did critical reviews. Data availability statement All data included in this study can be provided by contacting [email protected] . Conflicts of Interest and Source of Funding The authors declare no conflict of interest concerning the materials or methods used in this study or the findings presented in this paper. Additional Information Correspondence and requests for materials should be addressed to Y.-H.K. IRB Approval: The study protocol was approved by the Institutional Review Board of Asan Medical Center (IRB No. 2019-1397) References Kim, K. H. et al. Is Low-Lying Optic Chiasm an Obstacle to an Endoscopic Endonasal Approach for Retrochiasmatic Craniopharyngiomas? (Korean Society of Endoscopic Neurosurgery -003). World Neurosurg 114 , e306-e316, doi:10.1016/j.wneu.2018.02.178 (2018). Kim, Y. H. et al. Clinical outcomes of an endoscopic transclival and transpetrosal approach for primary skull base malignancies involving the clivus. J Neurosurg 128 , 1454-1462, doi:10.3171/2016.12.JNS161920 (2018). Kong, D. S. et al. Selection of endoscopic or transcranial surgery for tuberculum sellae meningiomas according to specific anatomical features: a retrospective multicenter analysis (KOSEN-002). J Neurosurg 130 , 838-847, doi:10.3171/2017.11.JNS171337 (2018). Park, H. H. et al. Endoscopic transorbital and endonasal approach for trigeminal schwannomas: a retrospective multicenter analysis (KOSEN-005). J Neurosurg , 1-10, doi:10.3171/2019.3.JNS19492 (2019). Kassam, A. B. et al. Endoscopic reconstruction of the cranial base using a pedicled nasoseptal flap. Neurosurgery 63 , ONS44-52; discussion ONS52-43, doi:10.1227/01.NEU.0000297074.13423.F5 (2008). Hadad, G. et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 116 , 1882-1886, doi:10.1097/01.mlg.0000234933.37779.e4 (2006). Hu, F. et al. Combined use of a gasket seal closure and a vascularized pedicle nasoseptal flap multilayered reconstruction technique for high-flow cerebrospinal fluid leaks after endonasal endoscopic skull base surgery. World Neurosurg 83 , 181-187, doi:10.1016/j.wneu.2014.06.004 (2015). Zwagerman, N. T. et al. Does lumbar drainage reduce postoperative cerebrospinal fluid leak after endoscopic endonasal skull base surgery? A prospective, randomized controlled trial. J Neurosurg , 1-7, doi:10.3171/2018.4.JNS172447 (2018). Kitano, M. & Taneda, M. Icing and multilayering technique of injectable hydroxyapatite cement paste for cranial base reconstruction after transsphenoidal surgery: technical note. Neurosurgery 61 , E53-54; discussion E54, doi:10.1227/01.neu.0000289713.80178.ce (2007). Chung, S. B., Nam, D. H., Park, K., Kim, J. H. & Kong, D. S. Injectable hydroxyapatite cement patch as an on-lay graft for the sellar reconstructions following endoscopic endonasal approach. Acta Neurochir (Wien) 154 , 659-664; discussion 664, doi:10.1007/s00701-012-1293-5 (2012). Kim, Y. H. et al. Multi-Layer Onlay Graft Using Hydroxyapatite Cement Placement without Cerebrospinal Fluid Diversion for Endoscopic Skull Base Reconstruction. J Korean Neurosurg Soc 64 , 619-630, doi:10.3340/jkns.2020.0231 (2021). Lee, S. H. et al. Clinical Impact of Hydroxyapatite on the Outcome of Skull Base Reconstruction for Intraoperative High-Flow CSF Leak: A Propensity Score Matching Analysis. Front Oncol 12 , 906162, doi:10.3389/fonc.2022.906162 (2022). Hong, I. et al. Efficacy of hydroxyapatite-based skull base reconstruction for intraoperative high-flow cerebrospinal fluid leakage performed by less-experienced surgeons. Sci Rep 13 , 14886, doi:10.1038/s41598-023-42097-y (2023). Esposito, F., Dusick, J. R., Fatemi, N. & Kelly, D. F. Graded repair of cranial base defects and cerebrospinal fluid leaks in transsphenoidal surgery. Oper Neurosurg (Hagerstown) 60 , 295-303; discussion 303-294, doi:10.1227/01.NEU.0000255354.64077.66 (2007). Hong, S. D. et al. Olfactory outcomes after endoscopic pituitary surgery with nasoseptal "rescue" flaps: electrocautery versus cold knife. Am J Rhinol Allergy 28 , 517-519, doi:10.2500/ajra.2014.28.4109 (2014). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4146503","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":286180548,"identity":"5b5c6de9-983a-4927-8eaf-2918598d7aed","order_by":0,"name":"Minho Yang","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Minho","middleName":"","lastName":"Yang","suffix":""},{"id":286180550,"identity":"b551e52e-7821-4338-a0ff-fa536b551170","order_by":1,"name":"Gung Ju Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Gung","middleName":"Ju","lastName":"Kim","suffix":""},{"id":286180553,"identity":"9fe57713-9190-43d6-a420-c7de34c2d875","order_by":2,"name":"Juhee Jeon","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Juhee","middleName":"","lastName":"Jeon","suffix":""},{"id":286180554,"identity":"676df612-2487-41b3-b18b-1b96457a82c9","order_by":3,"name":"Yukyeng Byeon","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yukyeng","middleName":"","lastName":"Byeon","suffix":""},{"id":286180555,"identity":"cccbe01a-e3f0-43aa-8ff6-90067e76fbf1","order_by":4,"name":"Chaejin Lee","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Chaejin","middleName":"","lastName":"Lee","suffix":""},{"id":286180556,"identity":"3d29522d-4723-4f37-82ee-ef468fca4a8d","order_by":5,"name":"Ji Heui Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"Heui","lastName":"Kim","suffix":""},{"id":286180557,"identity":"f1e1532c-db24-4722-aca7-a2250c341b2c","order_by":6,"name":"Sang Woo Song","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Woo","lastName":"Song","suffix":""},{"id":286180558,"identity":"98f2cc5f-32c0-410c-aa8d-0cbef00eff95","order_by":7,"name":"Chang-Ki Hong","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Chang-Ki","middleName":"","lastName":"Hong","suffix":""},{"id":286180559,"identity":"8ed392cb-1aa9-493c-8884-8cf267291d5d","order_by":8,"name":"Jeong Hoon Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jeong","middleName":"Hoon","lastName":"Kim","suffix":""},{"id":286180560,"identity":"41d26536-4b6d-4bd3-be70-4b12b32dff72","order_by":9,"name":"Yong Hwy Kim","email":"","orcid":"","institution":"Seoul National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"Hwy","lastName":"Kim","suffix":""},{"id":286180561,"identity":"97d2e2d5-cc85-41d9-a67a-5519b2bb7652","order_by":10,"name":"Doo-Sik Kong","email":"","orcid":"","institution":"Samsung Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Doo-Sik","middleName":"","lastName":"Kong","suffix":""},{"id":286180562,"identity":"52a395f3-1e6c-4653-bfdd-1fc3f7c8f7e3","order_by":11,"name":"Young-Hoon Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYBACxgYgkcDwT87+eA9YgIePCC2MDQkMB4wZzpyBaGEDkQcIW3QgseFGDoRLUAvzjPTnDx7uuMPYOPPtwc+FOXYybAy8Bx9/wGfFjBzDhsQzz5iZpfOSpWduSwY6jC/ZAJ8tQC2MDYltzGxs0jkG0rzbmIFaeMwk8GtJfwjSwsMjecb4N++2epAW8x/4tSQAHdZ2WEJCgscMaMthsC14vc/Y88ZwRmJbmoEBT46ZNe+24zxszDzGEmfwaDFsT3/w8WebTf0G9jPGt3m3Vdvzs/cYfqjAp6UBQ4gZj3IQkCcgPwpGwSgYBaOAgQEAOqFJ4FPZO4MAAAAASUVORK5CYII=","orcid":"","institution":"Asan Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Young-Hoon","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2024-03-22 02:29:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4146503/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4146503/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54038930,"identity":"8f7fad05-df68-4f85-8131-29e24cfce77f","added_by":"auto","created_at":"2024-04-03 17:16:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1982649,"visible":true,"origin":"","legend":"\u003cp\u003e(A) The surgical dead space was filled with the Gelfoam\u003csup\u003e®\u003c/sup\u003e sponge. (B) The dural defect was blocked with the double-layered dural substitutes. (C) The injectable hydroxyapatite cement was applied for reconstruction after expanded endoscopic skull base surgery. (D) Then, we covered the entire surgical area with the vascular-pedicled nasoseptal flap.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4146503/v1/bdbbfc711f1d3eb2e93125d9.jpg"},{"id":54038929,"identity":"7394ffe9-9ab5-4e9e-8be6-342e7c0341c7","added_by":"auto","created_at":"2024-04-03 17:16:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":496077,"visible":true,"origin":"","legend":"\u003cp\u003eThis pictures depicts the schematic diagrams of the skull base reconstruction methods after expanded endoscopic surgery. (A) This figure shows the L-method. The surgical dead space was filled with the autologous abdominal fat graft, the dural defect was blocked with the double-layered dural substitutes, and covered with the nasoseptal flap. And cerebrospinal fluid was diverted through the lumbar drainage. (B) This figure represents the H-method. After filling the surgical dead space, the double-layered dural substitutes blocked the dural defect and the hydroxyapatite cement was applied. Finally, after covering the entire surgical area with the nasoseptal flap, the postoperative lumbar drainage was not performed.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4146503/v1/7880fb391366432e1e0ed71a.jpg"},{"id":54038932,"identity":"180d99f6-b323-47b5-9dcf-5460fa8758cf","added_by":"auto","created_at":"2024-04-03 17:16:53","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":354885,"visible":true,"origin":"","legend":"\u003cp\u003ePre- and postoperative images of huge pituitary adenoma with expanded endoscopic surgery. (A) Preoperative sagittal MRI image. (B) Postoperative sagittal MRI image. (C) Axial MRI image 2 weeks after surgery.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4146503/v1/e9714049eb0905bb4302b385.jpg"},{"id":59381361,"identity":"f078fb9c-8d43-4e7d-ae80-c21e4d72237a","added_by":"auto","created_at":"2024-07-01 05:39:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3638290,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4146503/v1/25c6ef05-0c6d-4ed7-9c9e-adcc05f0b941.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of the lumbar drain and the hydroxyapatite methods for cerebrospinal fluid leakage after endoscopic skull base surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRecently, endoscopic approaches via the nasal cavity have garnered interest for the removal of tumors in the skull base region, including pituitary tumors. Notably, the expanded endoscopic approach (EEA) has enabled nasal access for the treatment of tumors such as giant pituitary adenomas, meningiomas, and craniopharyngiomas, which previously required craniotomy and traditional skull base approaches.\u003csup\u003e1\u0026ndash;4\u003c/sup\u003e The nasoseptal mucosal flap graft, which is pedicled from the septal branch of sphenopalatine artery, has facilitated expanded endoscopic skull base surgeries without cerebrospinal fluid (CSF) leakage.\u003csup\u003e5,6\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDuring trans-sphenoidal surgery for pituitary tumors, traditional reconstruction methods entailed abdominal fat grafting and postoperative lumbar drainage (L-drainage) to manage CSF leakage.\u003csup\u003e5,7,8\u003c/sup\u003e Recent efforts have explored alternative reconstruction techniques, including nasoseptal flap grafts, fascia lata grafts, artificial dural grafts, coagulation component patches such as TachoSil\u0026reg;, and even methods utilizing artificial bone materials such as hydroxyapatite cement (HydroSet\u0026reg;) aimed at preventing CSF leakage.\u003csup\u003e9\u0026ndash;13\u003c/sup\u003e However, the most efficient and optimal method is under debate.\u003c/p\u003e \u003cp\u003eIn this study, we analyzed the outcomes of skull base reconstruction procedures performed at our institution to address CSF leakage during recent EEA. We compared two frequently employed techniques, viz. the insertion of postoperative L-drainage (L-method) and the use of injectable hydroxyapatite cement (HydroSet\u0026reg;) without L-drainage (H-method). The study aimed to conduct a comparative analysis of the efficacy, risks, and adverse effects of these two methods, contributing to the ongoing discourse on the most effective and optimal approach.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Cohort\u003c/h2\u003e \u003cp\u003eThis study was a retrospective review of a case series of a total of 768 patients who underwent endoscopic skull base surgery through the nasal cavity at our institution between 2016 and 2023. All available clinical information and neuroimaging data were collected the approval of our institutional review board. This study has been performed in accordance with the Declaration of Helskinki and the informed consent was obtained from all participants.\u003c/p\u003e \u003cp\u003eThe inclusion criteria for this study were as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) patients who underwent expanded endoscopic skull base surgery, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) grade 2 or 3 CSF leakage, (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) reconstruction was performed solely through the endoscopic intranasal approach, and (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) availability of complete clinical data before and after surgery.\u003c/p\u003e \u003cp\u003eCSF leakage was graded based on Kelly\u0026rsquo;s classification. Grade 2 CSF leakage involves a moderate leak with a defect in the sellar diaphragm, whereas grade 3 includes a significant defect in the sellar diaphragm with a substantial amount of CSF leakage.\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePatients who underwent surgery for pituitary tumors using the non-expanded trans-sphenoidal approach (n\u0026thinsp;=\u0026thinsp;448), those who did not experience grade 2 or 3 CSF leakage after expanded endoscopic skull base surgery (n\u0026thinsp;=\u0026thinsp;94), those who underwent skull base reconstruction through craniotomy (n\u0026thinsp;=\u0026thinsp;1), and patients with incomplete clinical data (n\u0026thinsp;=\u0026thinsp;14) were excluded from the study. Consequently, the study included 211 patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDemographic Data\u003c/h2\u003e \u003cp\u003eOf the 211 patients, 85 (40%) were men and 126 (60%) were women, with a median age of 55 years (range, 19\u0026ndash;74 years). The preoperative diagnoses were as follows: pituitary tumor (n\u0026thinsp;=\u0026thinsp;62, 29%), meningioma (n\u0026thinsp;=\u0026thinsp;50, 24%), craniopharyngioma (n\u0026thinsp;=\u0026thinsp;28, 13%), Rathke\u0026rsquo;s cleft cyst (n\u0026thinsp;=\u0026thinsp;17, 8%), sinonasal malignancy (n\u0026thinsp;=\u0026thinsp;16, 8%), chordoma or chondrosarcoma (n\u0026thinsp;=\u0026thinsp;8, 4%), and CSF leakage (n\u0026thinsp;=\u0026thinsp;22, 10%). The most common preoperative symptoms included visual disturbance (55%), headaches (19%), and sinonasal symptoms such as rhinorrhea, nasal congestion, and epistaxis (12%). The median tumor size was 2.8 cm (range, 0.5\u0026ndash;6.0 cm). The demographic and clinical data of the 211 patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eDemographical and clinical data of enrolled patients (n\u0026thinsp;=\u0026thinsp;211)\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\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue (range or %)\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\u003eNo of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e211\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian age (range; years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (19\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (40%)\u003c/p\u003e \u003cp\u003e126 (60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody mass index\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003eMedian value (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.4 (17.1\u0026ndash;37.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePast medical \u0026amp; social history\u003c/b\u003e\u003c/p\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003cp\u003eDrinking alcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (31%)\u003c/p\u003e \u003cp\u003e30 (14%)\u003c/p\u003e \u003cp\u003e47 (22%)\u003c/p\u003e \u003cp\u003e81 (38%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInitial symptoms \u0026amp; signs\u003c/b\u003e\u003c/p\u003e \u003cp\u003eVisual disturbance\u003c/p\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003cp\u003eSinonasal symptoms\u003c/p\u003e \u003cp\u003eDizziness\u003c/p\u003e \u003cp\u003eHormonal imbanlance\u003c/p\u003e \u003cp\u003eNeurological deterioration\u003c/p\u003e \u003cp\u003eCognitive dysfunction\u003c/p\u003e \u003cp\u003eNo symptoms \u0026amp; signs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117 (55%)\u003c/p\u003e \u003cp\u003e40 (19%)\u003c/p\u003e \u003cp\u003e25 (12%)\u003c/p\u003e \u003cp\u003e11 (5%)\u003c/p\u003e \u003cp\u003e9 (4%)\u003c/p\u003e \u003cp\u003e8 (4%)\u003c/p\u003e \u003cp\u003e6 (3%)\u003c/p\u003e \u003cp\u003e29 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative diagnosis\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePituitary adenoma\u003c/p\u003e \u003cp\u003eMeningioma\u003c/p\u003e \u003cp\u003eCraniopharyngioma\u003c/p\u003e \u003cp\u003eRathke\u0026rsquo;s cleft cyst\u003c/p\u003e \u003cp\u003eSinonasal malignancy\u003c/p\u003e \u003cp\u003eChordoma or Chondrosarcoma\u003c/p\u003e \u003cp\u003eCerebrospinal fluid leakage\u003c/p\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (29%)\u003c/p\u003e \u003cp\u003e50 (24%)\u003c/p\u003e \u003cp\u003e28 (13%)\u003c/p\u003e \u003cp\u003e17 (8%)\u003c/p\u003e \u003cp\u003e16 (8%)\u003c/p\u003e \u003cp\u003e8 (4%)\u003c/p\u003e \u003cp\u003e22 (10%)\u003c/p\u003e \u003cp\u003e8 (4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaximal diameter of tumors\u003c/b\u003e (cm)\u003c/p\u003e \u003cp\u003eMedian value (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8 (0.5\u0026ndash;6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003e*\u003c/sup\u003e No, number;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSkull Base Reconstruction Methods\u003c/h2\u003e \u003cp\u003eIn cases where a significant dead space remained after tumor resection with EEA, the space was filled using either Gelfoam\u0026reg; (Pfizer, New York, NY, USA) sponge or autologous abdominal fat graft (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). If a hole was created to the extent that restoration to the diaphragm sellae was feasible, it was patched using TachoSil\u0026reg; (Baxter, Deerfield, Illinois, USA) patch and the pituitary cavity was filled with Gelfoam\u0026reg; sponge. Deficient dura mater was reconstructed using an artificial dura mater substitute known as Duragen\u0026reg; (Integra, Princeton, NJ, USA) or autologous fascia lata graft. The latter was performed by creating a 5\u0026ndash;10-cm incision in the patient\u0026rsquo;s right thigh to obtain a direct graft or with a commercially available cadaveric fascia lata graft. When grafting the fascia lata, a double-layered construct consisting of an inlay and onlay was fabricated to minimize CSF leakage using the button-hole method (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe skull base defect was also repaired using an autologous bone graft harvested from the nasal septum or anterior wall of the sphenoid sinus. When the bones around the surgical defect were intact and well exposed without damage, and when there width the nasoseptal vascularized mucosal graft was sufficient with a low risk of postoperative infection, HydroSet\u0026reg; (Stryker, Kalamazoo, MI, USA), i.e., injectable hydroxyapatite cement, was used. The use of HydroSet\u0026reg; facilitated solid reconstruction with an artificial bone material, while simultaneously preventing CSF leakage (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). Additionally, the entire HydroSet\u0026reg; surface was covered with the previously harvested nasoseptal flap to prevent exposure within the nasal cavity (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed).\u003c/p\u003e \u003cp\u003eIn all cases where HydroSet\u0026reg; was not used, reconstruction of the skull base mucosa was achieved by covering it with the nasoseptal flap. To allow adhesion between each reconstructed layer, a minimum of 48 hours was required after surgery. Therefore, postoperative L-drainage was performed for CSF drainage via a spinal tap. Patients were typically restricted to minimal walking for an average of 5 days, and CSF was drained through the L-drain before removal, ensuring that no CSF leakage occurred at the surgical site, which was confirmed by examination by an otolaryngologist.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003ePostoperative L-drainage was performed in 83 (39%) of 211 patients, whereas HydroSet\u0026reg; was used without L-drainage in 103 patients (49%). No patient underwent L-drainage and HydroSet\u0026reg; reconstruction simultaneously. The technique of inserting the L-drain postoperatively was designated as the \u0026ldquo;L-method\u0026rdquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea), whereas the method of reconstruction using HydroSet\u0026reg; was designated as the \u0026ldquo;H-method\u0026rdquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb) and the two methods were compared. The preoperative diagnosis distribution, tumor size, surgical approach, operative time, extent of removal, method of reconstruction, occurrence of complications associated with reconstruction, frequency of postoperative CSF leakage, and length of hospital stay were compared.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStudent\u0026rsquo;s t-test was utilized for the comparison of continuous variables between the two groups, whereas Fisher's exact test and Pearson chi-square test were employed for categorical variables. The preoperative diagnosis distribution, maximum tumor diameter, distribution of endoscopic approach, need for reoperation, surgical time, extent of CSF leakage, extent of tumor removal, frequency of abdominal and fascia lata grafting, number of reconstruction layers, frequency of complications related to reconstruction, frequency of postoperative CSF leakage, length of hospital stay, and other variables were compared between the two reconstruction methods. All statistical analyses were conducted using IBM SPSS Statistics program version 21.0 (IBM Corp., Armonk, NY, USA). The \u003cem\u003ep\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOverall Surgical Results and Reconstruction-Related Complications\u003c/h2\u003e \u003cp\u003eThe most common approach was the trans-tubercular approach, which was performed in 159 (75%) of 211 patients, followed by the trans-sellar approach (n\u0026thinsp;=\u0026thinsp;24, 11%), trans-cribriform approach (n\u0026thinsp;=\u0026thinsp;14, 7%), trans-clival approach (n\u0026thinsp;=\u0026thinsp;10, 5%), and trans-pterygopalatine fossa approach (n\u0026thinsp;=\u0026thinsp;1, 2%). Fifty-six (27%) surgeries were reoperations due to tumor recurrence or CSF leakage. The median surgical duration was 250 min (range, 23\u0026ndash;783 min). Grade 2 CSF leakage occurred in 35 patients (17%), whereas grade 3 leakage occurred in 176 patients (83%).\u003c/p\u003e \u003cp\u003eNasoseptal mucosal grafts were used in almost all cases (n\u0026thinsp;=\u0026thinsp;207, 98%). Turbinate mucosal flap grafting was performed in 3 patients (1%) and vascular-pedicled muscle free grafting was employed in 1 patient (0.5%). Autologous abdominal fat grafting was performed in 26 patients (12%), whereas fascia lata grafting was performed in 41 patients (19%). Autologous grafting was used in 15 (7%) of 41 patients, and cadaveric fascia lata was used in 26 patients (12%). As mentioned earlier, HydroSet\u0026reg; was used in 103 patients (49%), and postoperative L-drainage in 83 patients (39%). Drainage was conducted for an average of 5 days (median, range: 2\u0026ndash;8 days), with an average of 150 mL of fluid (median, range: 100\u0026ndash;240 mL) drained per day.\u003c/p\u003e \u003cp\u003eNeither postoperative L-drainage nor HydroSet\u0026reg; was used in 25 patients (12%). Grade 2 CSF leakage occurred after surgery for large pituitary tumors in 21 patients and grade 3 in 2 patients. The leakage site was sealed with a TachoSil\u0026reg; patch, and reconstruction was performed using Duragen\u0026reg;, bone grafting, and nasoseptal flap grafting. In one case, after treating a chordoma using the trans-clival approach, the CSF leakage site was sealed using a TachoSil\u0026reg; patch, and the nasoseptal flap was employed for reconstruction. In another case, where CSF leakage occurred after surgery for a pituitary tumor, the L-drain was not inserted due to the presence of spontaneous subarachnoid hemorrhage before and after surgery. Instead, reconstruction was instituted using abdominal fat grafting, fascia lata grafting, and a nasoseptal flap. In all 25 cases, there were no complications such as postoperative CSF leakage.\u003c/p\u003e \u003cp\u003eThe tumor was completely or almost completely excised in 165 patients (87%). Complications related to reconstruction occurred in 18 patients (8%). Postoperative CSF leakage occurred in 12 patients (6%), and infection occurred in 4 patients (2%). One patient (0.5%) who developed septicemia occurred due to ventriculitis failed to regain consciousness, falling into a vegetative state, and was only capable of spontaneous breathing with the eyes open (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The overall surgical outcomes and complications of the 211 patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \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 results of enrolled patients (n\u0026thinsp;=\u0026thinsp;211)\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\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApproach\u003c/p\u003e \u003cp\u003eTrans-sellar\u003c/p\u003e \u003cp\u003eTrans-tubercular/planum\u003c/p\u003e \u003cp\u003eTrans-cribriform\u003c/p\u003e \u003cp\u003eTrans-clival\u003c/p\u003e \u003cp\u003eTrans-cavernous\u003c/p\u003e \u003cp\u003eTrans-PPF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (11%)\u003c/p\u003e \u003cp\u003e159 (75%)\u003c/p\u003e \u003cp\u003e14 (7%)\u003c/p\u003e \u003cp\u003e10 (5%)\u003c/p\u003e \u003cp\u003e3 (1%)\u003c/p\u003e \u003cp\u003e1 (1%)\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\u003eRevision operation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOperation time (min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250 (23\u0026ndash;783)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade of CSF leakage\u003c/b\u003e\u003c/p\u003e \u003cp\u003eGrade 2\u003c/p\u003e \u003cp\u003eGrade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (17%)\u003c/p\u003e \u003cp\u003e176 (83%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePedicled mucosal flap\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNasoseptal flap\u003c/p\u003e \u003cp\u003eTurbinate flap\u003c/p\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e207 (98%)\u003c/p\u003e \u003cp\u003e3 (1%)\u003c/p\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbdominal fat graft\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFascia lata graft\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003cp\u003eCadaveric\u003c/p\u003e \u003cp\u003e\u003cb\u003eAcellular dermal matrix\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (7%)\u003c/p\u003e \u003cp\u003e26 (12%)\u003c/p\u003e \u003cp\u003e135 (64%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutologous bone graft\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHydroxyapatite\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (49%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostop L-drainage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83 (39%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of L-drainage\u003c/b\u003e (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6 CR7\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAmount of daily drainage\u003c/b\u003e (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (100\u0026ndash;240)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtent of removal\u003c/b\u003e\u003c/p\u003e \u003cp\u003eGross total removal\u003c/p\u003e \u003cp\u003eNear total removal\u003c/p\u003e \u003cp\u003eSubtotal removal\u003c/p\u003e \u003cp\u003ePartial removal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131 (69%)\u003c/p\u003e \u003cp\u003e34 (18%)\u003c/p\u003e \u003cp\u003e19 (10%)\u003c/p\u003e \u003cp\u003e5 (3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReconstruction-related Cx\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative CSF leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative infection\u003c/p\u003e \u003cp\u003ePostoperative compression\u003c/p\u003e \u003cp\u003eBrain herniation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2%)\u003c/p\u003e \u003cp\u003e2 (1%)\u003c/p\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative hospital stay\u003c/b\u003e (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3\u0026ndash;38)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003e*\u003c/sup\u003e Median value (range); PPF, pterygopalatine fossa; CSF, cerebrospinal fluid; L-drainage, lumbar drainage; Cx, complications\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eComparison of Surgical Outcomes between the L- and H-Methods\u003c/h2\u003e \u003cp\u003eThere were no differences in the distribution of age, sex, and obesity between the two methods. Among patients who underwent the L-method, the most common diagnosis was pituitary adenoma (n\u0026thinsp;=\u0026thinsp;25, 30%), followed by CSF leakage (n\u0026thinsp;=\u0026thinsp;16, 19%), malignant tumor in the nasal cavity (n\u0026thinsp;=\u0026thinsp;14, 17%), Rathke's cleft cyst (n\u0026thinsp;=\u0026thinsp;7, 8%), craniopharyngioma (n\u0026thinsp;=\u0026thinsp;6, 7%), meningioma (n\u0026thinsp;=\u0026thinsp;5, 6%), and chordoma or chondrosarcoma (n\u0026thinsp;=\u0026thinsp;3, 4%). In contrast, meningiomas, particularly tuberculum sellae meningiomas, were the most common diagnoses among patients who underwent the H-method, occurring in 45 patients (44%), followed by craniopharyngiomas in 22 patients (22%), pituitary adenomas in 15 patients (15%), Rathke's cleft cysts in 10 patients (10%), and other tumors in 6 patients (6%), showing a significant difference compared to the distribution of patients who underwent reconstruction with the L-method (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean maximum diameter (3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 cm) in patients who underwent L-drainage was significantly larger than that (2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9cm) in patients treated with the H-method (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn the L-method group, the trans-tubercular approach was used in 45 patients (58%), the trans-sellar approach in 15 patients (18%), and the trans-cribriform approach was employed in 13 patients (16%). In contrast, in the H-method group, the trans-tubercular approach was used in 95 patients (95%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The frequency of reoperation was higher in the L-method with 36 patients (43%) compared to 13 patients (13%) in the H-method (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Grade 3 CSF leakage occurred in 71 patients (86%) who underwent L-drainage, whereas it occurred in 101 patients (98%) who underwent the H-method (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eAbdominal fat grafting and autologous bone grafting were performed more frequently in the L-method in 23 (28%) and 26 patients (31%), respectively, compared to 2 patients each (2%) in the H-method (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In the L-method group, fascia lata grafting was used in 26 patients (31%), including 15 autologous grafts (18%) and 11 cadaveric grafts (13%), which was significantly higher compared to only cadaveric graft in 13 patients (13%) in the H-method (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.003). The surgical outcomes and risks of the L- and H-methods are summarized and compiled in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\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\u003eComparison between the lumbar drainage method (L-method) and the hydroxyapatite method (H-method)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL-method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\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\u003eNo of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.461\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (43%)\u003c/p\u003e \u003cp\u003e47 (57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (35%)\u003c/p\u003e \u003cp\u003e67 (65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody mass index\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.587\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative diagnosis\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePituitary adenoma\u003c/p\u003e \u003cp\u003eMeningioma\u003c/p\u003e \u003cp\u003eCraniopharyngioma\u003c/p\u003e \u003cp\u003eSinonasal malignancy\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRathke\u0026rsquo;s cleft cyst\u003c/p\u003e \u003cp\u003eChordoma or Chondrosarcoma\u003c/p\u003e \u003cp\u003eCerebrospinal fluid leakage\u003c/p\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (30%)\u003c/p\u003e \u003cp\u003e5 (6%)\u003c/p\u003e \u003cp\u003e6 (7%)\u003c/p\u003e \u003cp\u003e14 (17%)\u003c/p\u003e \u003cp\u003e7 (8%)\u003c/p\u003e \u003cp\u003e3 (4%)\u003c/p\u003e \u003cp\u003e16 (19%)\u003c/p\u003e \u003cp\u003e7 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (15%)\u003c/p\u003e \u003cp\u003e45 (44%)\u003c/p\u003e \u003cp\u003e22 (22%)\u003c/p\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003cp\u003e10 (10%)\u003c/p\u003e \u003cp\u003e4 (4%)\u003c/p\u003e \u003cp\u003e5 (5%)\u003c/p\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaximal diameter of tumors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eApproach\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTrans-sellar\u003c/p\u003e \u003cp\u003eTrans-tubercular/planum\u003c/p\u003e \u003cp\u003eTrans-cribriform\u003c/p\u003e \u003cp\u003eTrans-clival\u003c/p\u003e \u003cp\u003eTrans-cavernous\u003c/p\u003e \u003cp\u003eTrans-PPF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (18%)\u003c/p\u003e \u003cp\u003e45 (58%)\u003c/p\u003e \u003cp\u003e13 (16%)\u003c/p\u003e \u003cp\u003e5 (6%)\u003c/p\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2%)\u003c/p\u003e \u003cp\u003e95 (95%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e3 (3%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRevision operation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOperation time\u003c/b\u003e (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e256\u0026thinsp;\u0026plusmn;\u0026thinsp;154\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e285\u0026thinsp;\u0026plusmn;\u0026thinsp;108\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade of CSF leakage\u003c/b\u003e\u003c/p\u003e \u003cp\u003eGrade 2\u003c/p\u003e \u003cp\u003eGrade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (14%)\u003c/p\u003e \u003cp\u003e71 (86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2%)\u003c/p\u003e \u003cp\u003e101 (98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbdominal fat graft\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFascia lata graft\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003cp\u003eCadaveric\u003c/p\u003e \u003cp\u003e\u003cb\u003eAcellular dermal matrix\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (18%)\u003c/p\u003e \u003cp\u003e11 (13%)\u003c/p\u003e \u003cp\u003e45 (54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e13 (13%)\u003c/p\u003e \u003cp\u003e74 (72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutologous bone graft\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReconstruction-related Cx\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.326\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative CSF leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative stay\u003c/b\u003e (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e* Mean value\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; L-drainage, lumbar drainage; No, number; PPF, pterygopalatine fossa; CSF, cerebrospinal fluid; Cx, complications\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparison of Complications between the L- and H-Methods\u003c/h2\u003e \u003cp\u003eComplications related to reconstruction occurred in 10 patients (11%) in the L-method, compared to 8 patients (8%) in the H-method, but the difference lacked statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.326). The 10 complications in the L-method included 8 cases (10%) of CSF leakage, 1 case of optic nerve compression by reconstruction materials, and 1 case of brain tissue herniation through the bone defect. The 8 complications in the H-method included 4 cases (4%) of CSF leakage and 4 cases (4%) of infection.\u003c/p\u003e \u003cp\u003eConsequently, postoperative CSF leakage occurred in 10% (8/83) of cases in the L-method and 4% (4/103) of cases in the H-method, with no statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.112). However, postoperative infection occurred only in the H-method group in 4 cases (4%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.070). Nonetheless, the length of hospital stay was significantly shorter with the H-method, at 6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 days, compared to 10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3 days in the L-method (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith the advent of endoscopic surgery for simple pituitary adenomas and tumors involving the entire skull base, the indications for expanded endoscopic skull base surgery have undergone gradual expansion. The increasing application of endoscopic surgery for skull base tumors is attributed to the development of effective techniques such as vascularized nasoseptal mucosal grafting, which provides adequate blood supply and effectively reconstructs the skull base region. This advancement has addressed one of the most challenging hurdles in skull base surgery, which is effectively preventing CSF leakage.\u003csup\u003e5,6\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNasoseptal mucosal flap grafting was used in 98% of patients in this study. Although there are drawbacks to the nasoseptal flap, such as nasal mucosa damage and olfactory dysfunction, these issues can be minimized by reducing the use of monopolar electrocautery and incising the mucosa with a knife or scissors.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough the nasoseptal flap can significantly reduce CSF leakage, it takes time for the graft to adhere completely to the skull base bone or normal mucosa in the surgical area. The exact duration required for the graft to adhere sufficiently to effectively prevent CSF leakage has not been established, but it is known to take a minimum of 2 to 7 days.\u003csup\u003e5,6\u003c/sup\u003e If CSF leakage is not effectively prevented or diverted before the adherence of the nasoseptal flap, CSF leakage can occur despite the use of grafting. Therefore, traditionally, L-drainage was the most frequently used method to divert CSF for a certain period of time after surgery.\u003csup\u003e8\u003c/sup\u003e The use of the lumbar catheter to drain a certain amount of CSF per day can reduce intracranial pressure and pressure on the skull base region involved in surgery, thereby decreasing the risk of CSF leakage at the surgical site. Recent prospective studies have also demonstrated that L-drainage significantly reduces CSF leakage compared to non-use of this method.\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHowever, inserting an L-drainage catheter for a certain period of time after surgery can make patients extremely uncomfortable and often necessitates bed rest, preventing them from engaging in any activity. Although rare, prolonged bed rest increases the risk of infections such as pneumonia and can lead to serious complications such as pulmonary thromboembolism and deep vein thrombosis. Moreover, prolonged drainage of large amounts of CSF carries the risk of serious complications such as subdural hemorrhage and downward herniation of the brain. Therefore, recent efforts have focused on avoiding the use of L-drainage whenever possible or minimizing the duration and amount of drainage if its use is necessary.\u003c/p\u003e \u003cp\u003eHydroxyapatite cement has been used as an artificial bone material for reconstructing defects after cranial surgery for quite some time. Hydroset\u0026reg; is a hydroxyapatite cement product that can be instilled using a syringe, making it suitable for use in the skull base region through the nasal cavity. Hydroset\u0026reg; consists of a powder form of hydroxyapatite mixed with a liquid adhesive, which hardens into a solid when exposed to moisture. Before hardening, it exists in a semi-solid state, allowing it to be shaped and molded in the desired form and quantity, achieving some degree of adhesion to the surrounding tissues. Consequently, some institutions initially proposed the potential use of Hydroset\u0026reg; as a reconstructive material following endoscopic skull base surgery.\u003csup\u003e9,10\u003c/sup\u003e If Hydroset\u0026reg; can effectively seal the skull base defect without the need for postoperative L-drainage and successfully address CSF leakage, it could indeed be considered as a new material for skull base reconstruction.\u003c/p\u003e \u003cp\u003eAccording to early reports from some institutions, the use of Hydroset\u0026reg; may lead to delayed CSF leakage, and exposure of the material within the nasal cavity may cause various nasal problems such as recurrent crust formation. Additionally, as it is an artificial material (rather than an autologous graft), the possibility of serious infections must also be considered. Serious ventriculitis occurred in initially in cases of giant pituitary adenomas treated in our study. Therefore, despite its potential benefits, the use of Hydroset\u0026reg; as a reconstructive material warrants meticulous evaluation, given its potential complications.\u003c/p\u003e \u003cp\u003eThese issues can be overcome by covering the exposed area with a large nasoseptal flap after Hydroset\u0026reg; application and adequate administration of antibiotics postoperatively. Immediate CSF leakage after surgery can be prevented with Hydroset\u0026reg;, whereas delayed leakage can be averted by double sealing with the adhered nasoseptal flap. Multiple layers of reconstructive materials can effectively prevent CSF leakage.\u003csup\u003e7\u003c/sup\u003e In the event of grade 2 or 3 CSF leakage, postoperative infection is always a significant concern. Therefore, a triple antibiotic regimen consisting of vancomycin, third-generation cephalosporins, and metronidazole can effectively reduce the risk of postoperative infection. In our study, bacterial infections did not occur after the use of triple antibiotic therapy, and only one case of delayed aseptic meningitis was reported.\u003c/p\u003e \u003cp\u003eAlthough rare, postoperative herniation of the brain through the defect site as well as nerve compression and injury are serious complications that can occur after endoscopic skull base surgery. Creating a solid reconstructive layer outside the surgical site using Hydroset\u0026reg; can help avert these complications.\u003csup\u003e9,10\u003c/sup\u003e Furthermore, the frequency of multi-layered reconstruction methods, such as abdominal fat grafting and autologous fascia lata grafting, was also reduced. Additionally, without the need for postoperative L-drainage, patients were able to resume movement sooner, thereby reducing the recovery period and effectively shortening hospital stay. Although the occurrence and probability of simple complications are important, patient satisfaction and quality of life after surgery are also crucial considerations.\u003c/p\u003e \u003cp\u003eThis study compared the most frequently used method of postoperative L-drainage with a newer reconstruction method using Hydroset\u0026reg;, from amongst the methods of defect repair after skull base expansion surgery, to compare the advantages and disadvantages of each method. However, this was not a randomized prospective study but a retrospective study, which could lead to bias in the selection and comparison of reconstruction methods. For example, in this study, the diseases and approaches targeted by the two methods did not show a uniform distribution. Therefore, randomized prospective studies are needed to conduct a more scientific comparison.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the event of grade 2 or grade 3 CSF leakage after expanded endoscopic skull base surgery, using a postoperative L-drainage as well as injecting hydroxyapatite cement without L-drainage were effective in preventing CSF leakage after surgery. The method of using hydroxyapatite cement without an L-drainage catheter allows for the omission of L-drain insertion postoperatively and shortens the postoperative hospital stay. However, surgeons should be aware of the increased risk of postoperative infections associated with the use of hydroxyapatite cement without an L-drain and implement appropriate precautions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received in support of this work, and no benefits in any form have been or will be received from a commercial party, directly or indirectly, related to the subject of this manuscript. The submitted manuscript does not contain information about any medical devices or drugs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM.Y. and Y.-H.K. wrote the main manuscript text. All authors reviewed the manuscript. M.Y., G.J.K., J.J., Y.B., C.L. and Y.-H.K. prepared figures and tables. J.H.K., S.W.S., C.-K.H., J.H.K., Y.H.K. and D.-S.K. supported basic materials. C.-K.H., Y.H.K., D.-S.K. and Y.-H.K. did critical reviews.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data included in this study can be provided by contacting [email protected].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest and Source of Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest concerning the materials or methods used in this study or the findings presented in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence and requests for materials should be addressed to Y.-H.K.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIRB Approval:\u0026nbsp;\u003c/strong\u003eThe study protocol was approved by the Institutional Review Board of Asan Medical Center (IRB No. 2019-1397)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKim, K. H.\u003cem\u003e et al.\u003c/em\u003e Is Low-Lying Optic Chiasm an Obstacle to an Endoscopic Endonasal Approach for Retrochiasmatic Craniopharyngiomas? (Korean Society of Endoscopic Neurosurgery -003). \u003cem\u003eWorld Neurosurg\u003c/em\u003e\u003cstrong\u003e114\u003c/strong\u003e, e306-e316, doi:10.1016/j.wneu.2018.02.178 (2018).\u003c/li\u003e\n\u003cli\u003eKim, Y. H.\u003cem\u003e et al.\u003c/em\u003e Clinical outcomes of an endoscopic transclival and transpetrosal approach for primary skull base malignancies involving the clivus. \u003cem\u003eJ Neurosurg\u003c/em\u003e\u003cstrong\u003e128\u003c/strong\u003e, 1454-1462, doi:10.3171/2016.12.JNS161920 (2018).\u003c/li\u003e\n\u003cli\u003eKong, D. S.\u003cem\u003e et al.\u003c/em\u003e Selection of endoscopic or transcranial surgery for tuberculum sellae meningiomas according to specific anatomical features: a retrospective multicenter analysis (KOSEN-002). \u003cem\u003eJ Neurosurg\u003c/em\u003e\u003cstrong\u003e130\u003c/strong\u003e, 838-847, doi:10.3171/2017.11.JNS171337 (2018).\u003c/li\u003e\n\u003cli\u003ePark, H. H.\u003cem\u003e et al.\u003c/em\u003e Endoscopic transorbital and endonasal approach for trigeminal schwannomas: a retrospective multicenter analysis (KOSEN-005). \u003cem\u003eJ Neurosurg\u003c/em\u003e, 1-10, doi:10.3171/2019.3.JNS19492 (2019).\u003c/li\u003e\n\u003cli\u003eKassam, A. B.\u003cem\u003e et al.\u003c/em\u003e Endoscopic reconstruction of the cranial base using a pedicled nasoseptal flap. \u003cem\u003eNeurosurgery\u003c/em\u003e\u003cstrong\u003e63\u003c/strong\u003e, ONS44-52; discussion ONS52-43, doi:10.1227/01.NEU.0000297074.13423.F5 (2008).\u003c/li\u003e\n\u003cli\u003eHadad, G.\u003cem\u003e et al.\u003c/em\u003e A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. \u003cem\u003eLaryngoscope\u003c/em\u003e\u003cstrong\u003e116\u003c/strong\u003e, 1882-1886, doi:10.1097/01.mlg.0000234933.37779.e4 (2006).\u003c/li\u003e\n\u003cli\u003eHu, F.\u003cem\u003e et al.\u003c/em\u003e Combined use of a gasket seal closure and a vascularized pedicle nasoseptal flap multilayered reconstruction technique for high-flow cerebrospinal fluid leaks after endonasal endoscopic skull base surgery. \u003cem\u003eWorld Neurosurg\u003c/em\u003e\u003cstrong\u003e83\u003c/strong\u003e, 181-187, doi:10.1016/j.wneu.2014.06.004 (2015).\u003c/li\u003e\n\u003cli\u003eZwagerman, N. T.\u003cem\u003e et al.\u003c/em\u003e Does lumbar drainage reduce postoperative cerebrospinal fluid leak after endoscopic endonasal skull base surgery? A prospective, randomized controlled trial. \u003cem\u003eJ Neurosurg\u003c/em\u003e, 1-7, doi:10.3171/2018.4.JNS172447 (2018).\u003c/li\u003e\n\u003cli\u003eKitano, M. \u0026amp; Taneda, M. Icing and multilayering technique of injectable hydroxyapatite cement paste for cranial base reconstruction after transsphenoidal surgery: technical note. \u003cem\u003eNeurosurgery\u003c/em\u003e\u003cstrong\u003e61\u003c/strong\u003e, E53-54; discussion E54, doi:10.1227/01.neu.0000289713.80178.ce (2007).\u003c/li\u003e\n\u003cli\u003eChung, S. B., Nam, D. H., Park, K., Kim, J. H. \u0026amp; Kong, D. S. Injectable hydroxyapatite cement patch as an on-lay graft for the sellar reconstructions following endoscopic endonasal approach. \u003cem\u003eActa Neurochir (Wien)\u003c/em\u003e\u003cstrong\u003e154\u003c/strong\u003e, 659-664; discussion 664, doi:10.1007/s00701-012-1293-5 (2012).\u003c/li\u003e\n\u003cli\u003eKim, Y. H.\u003cem\u003e et al.\u003c/em\u003e Multi-Layer Onlay Graft Using Hydroxyapatite Cement Placement without Cerebrospinal Fluid Diversion for Endoscopic Skull Base Reconstruction. \u003cem\u003eJ Korean Neurosurg Soc\u003c/em\u003e\u003cstrong\u003e64\u003c/strong\u003e, 619-630, doi:10.3340/jkns.2020.0231 (2021).\u003c/li\u003e\n\u003cli\u003eLee, S. H.\u003cem\u003e et al.\u003c/em\u003e Clinical Impact of Hydroxyapatite on the Outcome of Skull Base Reconstruction for Intraoperative High-Flow CSF Leak: A Propensity Score Matching Analysis. \u003cem\u003eFront Oncol\u003c/em\u003e\u003cstrong\u003e12\u003c/strong\u003e, 906162, doi:10.3389/fonc.2022.906162 (2022).\u003c/li\u003e\n\u003cli\u003eHong, I.\u003cem\u003e et al.\u003c/em\u003e Efficacy of hydroxyapatite-based skull base reconstruction for intraoperative high-flow cerebrospinal fluid leakage performed by less-experienced surgeons. \u003cem\u003eSci Rep\u003c/em\u003e\u003cstrong\u003e13\u003c/strong\u003e, 14886, doi:10.1038/s41598-023-42097-y (2023).\u003c/li\u003e\n\u003cli\u003eEsposito, F., Dusick, J. R., Fatemi, N. \u0026amp; Kelly, D. F. Graded repair of cranial base defects and cerebrospinal fluid leaks in transsphenoidal surgery. \u003cem\u003eOper Neurosurg (Hagerstown)\u003c/em\u003e\u003cstrong\u003e60\u003c/strong\u003e, 295-303; discussion 303-294, doi:10.1227/01.NEU.0000255354.64077.66 (2007).\u003c/li\u003e\n\u003cli\u003eHong, S. D.\u003cem\u003e et al.\u003c/em\u003e Olfactory outcomes after endoscopic pituitary surgery with nasoseptal \u0026quot;rescue\u0026quot; flaps: electrocautery versus cold knife. \u003cem\u003eAm J Rhinol Allergy\u003c/em\u003e\u003cstrong\u003e28\u003c/strong\u003e, 517-519, doi:10.2500/ajra.2014.28.4109 (2014).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"expanded endoscopic surgery, skull base reconstruction, hydroxyapatite, lumbar drainage, infection","lastPublishedDoi":"10.21203/rs.3.rs-4146503/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4146503/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to compare the clinical outcomes and risk of two skull base reconstruction methods after expanded endoscopic skull base approach (EEA), viz. postoperative cerebrospinal fluid (CSF) lumbar drainage (L-method) and injectable hydroxyapatite cement without lumbar drainage (H-method).\u003c/p\u003e\n\u003cp\u003eWe enrolled 211 consecutive patients with grade 2 or 3 CSF leakage after EEA. The most common preoperative diagnoses were pituitary adenoma (n=62, 29%), meningioma (n=50, 24%), and craniopharyngioma (n=28, 13%). Vascularized nasoseptal flaps were used in most cases (98%). We used the L-method and H-method in 83 (39%) and 103 patients (49%), respectively.\u003c/p\u003e\n\u003cp\u003eThe overall reconstruction-related complication and CSF leakage rates were 8% (18/211) and 6% (12/211), respectively. The complications included CSF leakage (n=12), infection (n=4), postoperative compression (n=2), and brain herniation (n=1). The complication and CSF leakage rates did not differ significantly between the L-method (12% and 10%, respectively) and H-method (8% and 4%, respectively) (\u003cem\u003eP\u003c/em\u003e=0.326 and 0.112, respectively). All infections occurred in the H-method (\u003cem\u003eP\u003c/em\u003e=0.070). Postoperative hospital stay was significantly shorter with the H-method (6.9 days) compared to the L-method (10.0 days) (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eSkull base reconstruction using hydroxyapatite effectively prevented CSF leakage and ensured patient comfort and shorter hospitalization without postoperative lumbar drainage, although postoperative infection requires consideration.\u003c/p\u003e","manuscriptTitle":"Comparison of the lumbar drain and the hydroxyapatite methods for cerebrospinal fluid leakage after endoscopic skull base surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-03 17:16:48","doi":"10.21203/rs.3.rs-4146503/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cb1b9067-39c5-4903-be9e-4300f882b351","owner":[],"postedDate":"April 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":30121569,"name":"Biological sciences/Neuroscience"},{"id":30121570,"name":"Biological sciences/Neuroscience/Diseases of the nervous system"},{"id":30121571,"name":"Biological sciences/Neuroscience/Diseases of the nervous system/Cancer in the nervous system"},{"id":30121572,"name":"Health sciences/Oncology/Surgical oncology"}],"tags":[],"updatedAt":"2024-10-04T04:38:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-03 17:16:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4146503","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4146503","identity":"rs-4146503","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}