Comparison of the Lumbar Drain and the Hydroxyapatite Methods for Cerebrospinal Fluid Leakage after Endoscopic Skull Base Surgery
Article information
Abstract
Objective
This study aimed to compare the clinical outcomes and risk of two skull base reconstruction methods after expanded expanded endoscopic approach (EEA), viz. postoperative cerebrospinal fluid (CSF) lumbar drainage (L-method) and injectable hydroxyapatite cement without lumbar drainage (H-method).
Methods
We enrolled 211 consecutive patients with grade 2 or 3 intraoperative CSF leakage during 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.
Results
The overall reconstruction-related complication and postoperative CSF leakage rates were 8% (18/211) and 6% (12/211), respectively. The complications included postoperative CSF leakage (n=12), infection (n=4), postoperative optic nerve compression (n=1), and brain herniation (n=1). The postoperative 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). Postoperative hospital stay was significantly shorter with the H-method (6.9 days) compared to the L-method (10.0 days) (p<0.001). However, the postoperative infection rate of the H-method (n=4) was higher than that of the L-method (n=0; p=0.070).
Conclusion
Skull base reconstruction using hydroxyapatite effectively prevented postoperative CSF leakage and ensured patient comfort and shorter hospitalization without postoperative lumbar drainage, although postoperative infection requires consideration.
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 [8,9,12,14]. The nasoseptal mucosal flap graft, which is pedicled from the septal branch of sphenopalatine artery, has facilitated expanded endoscopic skull base surgeries without postoperative cerebrospinal fluid (CSF) leakage [3,7].
During trans-sphenoidal surgery for pituitary tumors, traditional reconstruction methods entailed abdominal fat grafting and postoperative lumbar drainage (L-drainage) to manage CSF leakage [6,7,15]. 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 postoperative CSF leakage [1,4,10,11,13]. 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 postoperative CSF leakage after 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.
MATERIALS AND METHODS
All available clinical information and neuroimaging data were collected the approval of the Institutional Review Board (IRB) of Asan Medical Center (IRB No. 2019-1397). This study has been performed in accordance with the Declaration of Helsinki. This study did not require informed consent, and the IRB approved the waiver of informed consent in this retrospective study.
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.
The inclusion criteria for this study were as follows : 1) patients who underwent expanded endoscopic skull base surgery, 2) grade 2 or 3 intraoperative 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 [2].
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 intraoperative CSF leakage during 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). 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). The demographic and clinical data of the 211 patients are summarized in Table 1.
Demographical and clinical data of enrolled patients (n=211)
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. 1A). If a hole was created to the extent that restoration to the diaphragm sellae was feasible, it was patched using TachoSil® (Baxter, Deerfield, IL, 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), an acellular dermal matrix known as Megaderm® (Cowellmedi, Villanova, PA, USA), or 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 postoperative CSF leakage using the button-hole method (Fig. 1B). In the series included in this study, fascia lata graft was used in the early stages, but artificial materials were used to prevent it in the latter stages. Of course, in the case of reoperation due to infection or postoperative CSF leakage, an autologous reconstruction material was used if possible.
A : The surgical dead space was filled with the Gelfoam® (Pfizer, New York, NY, USA) 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.
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 their 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. 1C). Additionally, the entire HydroSet® surface was covered with the previously harvested nasoseptal flap to prevent exposure within the nasal cavity (Fig. 1D).
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. 2A), whereas the method of reconstruction using HydroSet® was designated as the “H-method” (Fig. 2B) 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.
This 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.
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 intraoperative 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 postoperative CSF leakage. The median surgical duration was 250 minutes (range, 23–783). 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 three patients (1%) and vascular-pedicled muscle free grafting was employed in one 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), with an average of 150 mL of fluid (median; range, 100–240) drained per day.
Neither postoperative L-drainage nor HydroSet® was used in 25 patients (12%). Grade 2 intraoperative CSF leakage occurred during surgery for large pituitary tumors in 21 patients and grade 3 in two 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 postoperative 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 four 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.
Pre- and postoperative images of huge pituitary adenoma with expanded endoscopic surgery. A : Preoperative sagittal magnetic resonance imaging (MRI) image identified a huge pituitary adenoma. B : The tumor was completely removed after expanded endoscopic surgery. C : Two weeks postoperative axial MRI image showed contrast enhancement across the whole ventricle wall, and it was diagnosed as ventriculitis.
Surgical results of enrolled patients (n=211)
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 six 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±0.9 cm) 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 intraoperative 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 two 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.
Comparison between the lumbar drainage method (L-method) and the hydroxyapatite method (H-method)
Comparison of complications between the L- and H-methods
Complications related to reconstruction occurred in 10 patients (11%) in the L-method, compared to eight patients (8%) in the H-method, but the difference lacked statistical significance (p=0.326). The 10 complications in the L-method included eight cases (10%) of postoperative CSF leakage, one case of optic nerve compression by reconstruction materials, and one case of brain tissue herniation through the bone defect. The eight complications in the H-method included four cases (4%) of postoperative CSF leakage and four 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). There was no significant difference in the incidence of postoperative CSF leakage according to the dural reconstructive materials (p=0.889). However, postoperative infection occurred only in the H-method group in four 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). The hospitalization periods of the four patients who developed the postoperative infection in the H-method were 4, 12, 22, and 38 days, respectively.
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 postoperative CSF leakage [3,7].
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 [5].
Although the nasoseptal flap can significantly reduce postoperative 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 postoperative CSF leakage has not been established, but it is known to take a minimum of 2 to 7 days [3,7]. If CSF leakage is not effectively prevented or diverted before the adherence of the nasoseptal flap, postoperative 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 [15]. 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 postoperative CSF leakage at the surgical site. Recent prospective studies have also demonstrated that L-drainage significantly reduces postoperative CSF leakage compared to non-use of this method [15].
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 [1,11]. 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 postoperative CSF leakage [6]. In the event of grade 2 or 3 intraoperative 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 [1,11]. 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.
In addition, since hydroxyapatite is a relatively new reconstruction method that has not been used recently, it is necessary to be very careful about the long-term effects and side effects of this method. For example, care should be taken about what effect hydroxyapatite may have when radiation therapy is performed to prevent recurrence of malignant tumors or when reoperation is performed due to recurrence of tumors. Moreover, one of the important limitations of this study is that it includes both benign tumors such as pituitary adenoma and meningioma and malignant tumors such as chordoma. In the case of malignant tumors, radiotherapy or proton therapy should be performed after surgery, and in many cases, recurrence and reoperation are performed later, so more attention should be paid to skull base reconstruction than to benign tumors. Fortunately, hydroxyapatite did not cause any special problems after radiotherapy, and reoperation helped with the dissection. In the case of not using hydroxyapatite, the adhesion between the dural layer and the nasoseptal flap occurred severely, but in the case of using hydroxyapatite, a bony layer was added between them to help with the dissection and reopening during reoperation. And, since the risk of postoperative CSF leakage and reconstruction methods differ according to various surgical approaches, more detailed analysis and research are needed according to each approach in the future.
Consequently, the two skull base reconstruction methods compared in this study are not mutually exclusive but complementary. The traditional L-method can be advantageous in cases where the sellar floor bone is thin and weak, such as large pituitary adenoma, or when the risk of infection is high, such as revision surgery. However, if the sellar floor bone is intact, such as meningioma and craniopharyngioma, and the H-method is used when the risk of post-operative infection is not high, patients can experience rapid recovery and discharge.
CONCLUSION
In the event of grade 2 or grade 3 intraoperative 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.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Informed consent
This type of study does not require informed consent.
Author contributions
Conceptualization : JHK, CKH, Yong Hwy Kim, DSK, Young-Hoon Kim; Data curation : MY, GJK, JJ, YB, CL; Formal analysis : MY, Young-Hoon Kim; Funding acquisition : JHK, Young-Hoon Kim; Methodology : MY, SWS, Young-Hoon Kim; Project administration : Young-Hoon Kim; Visualization : MY, Young-Hoon Kim; Writing - original draft : MY, Young-Hoon Kim; Writing - review & editing : Young-Hoon Kim
Data sharing
Data are available from the corresponding author on reasonable request.
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