A simple surgical technique for sellar closure after transsphenoidal resection of pituitary adenomas in the context of risk factors for cerebrospinal fluid leaks and meningitis

Moritz UeberschaerDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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Sophie KatzendoblerDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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Annamaria BiczokDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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Michael SchmutzerDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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Tobias GreveDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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Joerg-Christian TonnDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and
German Cancer Consortium (DKTK partner site Munich), Germany

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Jun ThorsteinsdottirDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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Walter RachingerDepartment of Neurosurgery, Ludwig-Maximilians-University, Munich; and

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OBJECTIVE

The transsphenoidal approach is the standard for most pituitary tumors. Despite low morbidity, postoperative CSF fistulas and meningitis are specific complications. Various surgical closure techniques for intraoperative CSF (iCSF) leak and sellar reconstruction have been described. For many years the authors have applied synthetic materials for iCSF leak repair and sellar closure in a standardized fashion in their department. Here they analyze the surgical outcome as well as risk factors for iCSF leak and meningitis.

METHODS

All patients with transsphenoidal resection of a pituitary adenoma performed by the same surgeon between January 2013 and December 2019 were screened retrospectively. A small amount of iCSF flow without a diaphragmatic defect was classified as a minor leak, and obvious CSF flow with or without a diaphragmatic defect was classified as a major leak. In case of iCSF leak, a fibrin- and thrombin-coated sponge was used to cover the diaphragmatic defect and another one was used for the sellar opening. A gelatin sponge was placed in the sphenoid sinus as an abutment. The primary and secondary outcomes were the number of postoperative CSF (pCSF) leaks and meningitis, respectively. Clinical, histological, and perioperative data from medical records were collected to identify risk factors for CSF leak and meningitis.

RESULTS

Of 417 transsphenoidal surgeries, 359 procedures in 348 patients with a median age of 54 years were included. There were 96 iCSF leaks (26.7%; 37.5% major, 62.5% minor). In 3 of 359 cases (0.8%) a pCSF fistula occurred, requiring revision surgery in 2 patients and a lumbar drain in 1 patient. Meningitis occurred in 3 of 359 cases (0.8%). All 3 patients recovered without sequelae after antibiotic therapy. According to univariate analysis, risk factors for iCSF leak were macroadenoma (p = 0.006) and recurrent adenoma (p = 0.032). An iCSF leak was found less often in functioning adenomas (p = 0.025). In multivariate analysis recurrent tumors remained as a risk factor (p = 0.021) for iCSF leak. Patients with iCSF leak were at increased risk for a pCSF leak (p = 0.005). A pCSF leak in turn represented the key risk factor for meningitis (p = 0.033).

CONCLUSIONS

Patients with macroadenomas and recurrent adenomas are especially at risk for iCSF leak. An iCSF leak in turn increases the risk for a pCSF leak, which carries the risk for meningitis. The authors’ surgical technique leads to a very low rate of pCSF leaks and meningitis without using autologous graft materials. Hence, this technique is safe and improves patient comfort by avoiding the disadvantages of autologous graft harvesting.

ABBREVIATIONS

iCSF = intraoperative CSF; pCSF = postoperative CSF.

OBJECTIVE

The transsphenoidal approach is the standard for most pituitary tumors. Despite low morbidity, postoperative CSF fistulas and meningitis are specific complications. Various surgical closure techniques for intraoperative CSF (iCSF) leak and sellar reconstruction have been described. For many years the authors have applied synthetic materials for iCSF leak repair and sellar closure in a standardized fashion in their department. Here they analyze the surgical outcome as well as risk factors for iCSF leak and meningitis.

METHODS

All patients with transsphenoidal resection of a pituitary adenoma performed by the same surgeon between January 2013 and December 2019 were screened retrospectively. A small amount of iCSF flow without a diaphragmatic defect was classified as a minor leak, and obvious CSF flow with or without a diaphragmatic defect was classified as a major leak. In case of iCSF leak, a fibrin- and thrombin-coated sponge was used to cover the diaphragmatic defect and another one was used for the sellar opening. A gelatin sponge was placed in the sphenoid sinus as an abutment. The primary and secondary outcomes were the number of postoperative CSF (pCSF) leaks and meningitis, respectively. Clinical, histological, and perioperative data from medical records were collected to identify risk factors for CSF leak and meningitis.

RESULTS

Of 417 transsphenoidal surgeries, 359 procedures in 348 patients with a median age of 54 years were included. There were 96 iCSF leaks (26.7%; 37.5% major, 62.5% minor). In 3 of 359 cases (0.8%) a pCSF fistula occurred, requiring revision surgery in 2 patients and a lumbar drain in 1 patient. Meningitis occurred in 3 of 359 cases (0.8%). All 3 patients recovered without sequelae after antibiotic therapy. According to univariate analysis, risk factors for iCSF leak were macroadenoma (p = 0.006) and recurrent adenoma (p = 0.032). An iCSF leak was found less often in functioning adenomas (p = 0.025). In multivariate analysis recurrent tumors remained as a risk factor (p = 0.021) for iCSF leak. Patients with iCSF leak were at increased risk for a pCSF leak (p = 0.005). A pCSF leak in turn represented the key risk factor for meningitis (p = 0.033).

CONCLUSIONS

Patients with macroadenomas and recurrent adenomas are especially at risk for iCSF leak. An iCSF leak in turn increases the risk for a pCSF leak, which carries the risk for meningitis. The authors’ surgical technique leads to a very low rate of pCSF leaks and meningitis without using autologous graft materials. Hence, this technique is safe and improves patient comfort by avoiding the disadvantages of autologous graft harvesting.

The transnasal transsphenoidal approach is the standard surgical approach nowadays for most pituitary tumors1 because it is associated with low morbidity and quick patient recovery,25 whereas the transcranial approach is reserved mainly for large and complex adenomas.68 Nevertheless, it remains a challenge to further improve patient comfort and further reduce postoperative morbidity.

Until now, postoperative CSF (pCSF) leaks and infections of the CNS such as meningitis are two recurring complications that remain a matter of debate.25 Meticulous repair of intraoperative CSF (iCSF) leaks and sellar reconstruction are of utmost importance in order to avoid these complications. However, there is no standard surgical technique.9

A variety of methods for sellar and dural reconstruction have been described in which either autologous10,11 or synthetic tissue is used.1214 The use of fascia lata, nasoseptal flaps, or the transplantation of paraumbilical fat have been reported to reduce pCSF leaks,10,15 but they carry the risk of side effects and complications such as postoperative hematomas, pain or infections in the area of the graft, cosmetically unappealing abdominal and thigh scars, or anosmia. They can lead to patient discomfort, although the main surgical goal in terms of tumor resection without occurrence of a CSF fistula is achieved.2,16,17 A recent survey by Májovský et al. found that many neurosurgeons continue to use autologous material for sellar closure despite such potential complications.9

For many years we have been using a standardized technique for iCSF leak repair and sellar closure in which artificial material is used. Here, we revisited our technique and the surgical results in terms of the number of iCSF leaks, pCSF leaks, and CNS infections to challenge the more invasive methods with autologous material described above. In addition, risk factors for these complications were identified.

Methods

All patients undergoing transnasal transsphenoidal resection for a histologically proven pituitary adenoma between January 2013 and December 2019 were retrospectively screened. Patients with other tumor entities such as craniopharyngiomas or meningiomas were excluded because in our practice alternative techniques for dural repair and sellar closure are being used for extended transsphenoidal approaches and/or primarily intradural tumors.

All surgeries have been performed by the same surgeon, either by himself or by another surgeon under his intraoperative supervision. Only patients with documentation of iCSF leak repair and sellar reconstruction in the surgical report were included. If only a small amount of CSF flow without identification of a defect in the diaphragm was encountered, the leak was classified according to Esposito et al.10 as a minor leak (grade 1), whereas obvious CSF flow with or without a defect of the diaphragm was classified as a major leak (grade 2). The primary outcome measure was the number of pCSF leaks. The secondary outcome was the number of proven CNS infections. To identify risk factors for iCSF and pCSF leaks and CNS infections, clinical, histological, and perioperative data from the electronic medical record were collected and analyzed. Preoperative contrast-enhanced MR images were reviewed by a trained specialist in pituitary surgery for assessment of Knosp grading. The extent of resection was indicated according to the evaluation of postoperative MR images by the surgeon and/or radiologist at follow-up. This study has been approved by the local ethics committee.

Surgical Procedure

The transnasal transsphenoidal surgeries were performed either microsurgically, endoscopically, or with a combination of those methods. Disinfection of outer and inner nostrils was performed using a mucosal disinfectant (Octenisept). Afterward adrenaline-soaked cottonoids were placed in both nostrils and sterile draping was applied in a standard fashion. A mononostril approach was chosen for microsurgical procedures, and a binostril approach for endoscopic surgeries.

Sellar exposure extended routinely from one cavernous sinus to the other and from the sellar tubercle to the sellar floor; this was verified by radiography and/or neuronavigation. The dura mater was incised in a cruciate fashion. Ring curettes, dissectors, and grasping forceps were used for tumor resection.

In case of an iCSF leak after tumor resection, the defect in the diaphragm or suspected origin of CSF flow was covered by a thrombin- and fibrin-soaked gel foam (TachoSil). It was essential that the entire defect in the diaphragm, including the edges, was covered with this material. If no further CSF flow was evident during the Valsalva maneuver, a second thrombin- and fibrin-impregnated gel foam was used to cover the sellar opening. Here it was important that the edges of the sellar opening were cleared of mucosa, ensuring an adequate fixation of the gel foam. A gelatin sponge (Gelitta) was inserted in the sphenoid sinus for fixation (Fig. 1). Both nostrils were rinsed with iodine-containing disinfectant. Nasal tamponades were used for 1 to 2 days after surgery. A lumbar drain was not routinely placed.

FIG. 1.
FIG. 1.

Lateral view of the sphenoid sinus, the opened sella, and the diaphragm. iCSF leak (arrow) before (A) and after (B) application of the described technique. The asterisk marks the gelatin sponge, and the triangle marks the thrombin- and fibrin-soaked gel foam. © Moritz Ueberschaer, published with permission.

Statistical Analysis

A comparison of baseline variables between patient cohorts was performed using the chi-square test for categorical variables, the t-test for parametric variables, and the Mann-Whitney U-test for nonparametric variables. Multivariate analysis was performed using binary logistic regression models to estimate p value, hazard ratio, and 95% confidence interval. Statistical analysis was performed using a standard software package (SPSS Statistics version 25, IBM Corp.). The significance level was set at p < 0.05.

Results

Demographic Data

Among 417 surgeries for sellar tumors performed between January 2013 and December 2019, 368 transsphenoidal resections of pituitary adenomas in 357 patients were identified. Nine of 368 procedures had to be excluded because the surgical technique was not sufficiently documented (Fig. 2), and so 359 procedures in 348 patients were included in the final analysis.

FIG. 2.
FIG. 2.

Flowchart of patient selection and occurrence of CSF fistulas and meningitis.

The median age was 54 years (range 11–87 years), with a balanced sex distribution (177 female/171 male). There were 310 de novo and 49 recurrent tumors. In total, 307 of 359 tumors were macroadenomas, and 128 tumors were functioning adenomas according to preoperative laboratory tests (74 growth hormone, 27 adrenocorticotropic hormone, 25 prolactinoma, 2 thyroid-stimulating hormone). A total of 336 procedures were performed microsurgically, 20 endoscopically, and 3 were combined. Preoperative Knosp grade18,19 was available for 330 patients and the median grade was 2 (13 grade 0; 95 grade 1; 105 grade 2; 53 grade 3a; 17 grade 3b; 47 grade 4) (Table 1).

TABLE 1.

Demographic and descriptive data in patients who underwent surgery for pituitary adenomas

No./Total (%)No./Total w/ iCSF Leak (%)No./Total w/ pCSF Leak (%)No./Total w/ Meningitis (%)
Female sex177 (50.9)42/96 (43.8)2/3 (66.7)2/3 (66.7)
Median age in yrs, range54, 11–8754, 11–8738, 38–4338, 18–53
De novo tumors310 (86.4)75/310 (24.2)3/310 (0.97)3/310 (0.97)
Recurrent tumors49 (13.6)21/49 (42.9)0/49 (0)0/49 (0)
Microadenomas52 (14.5)6/52 (11.5)0/52 (0)0/52 (0)
Macroadenomas307 (85.5)90/307 (29.3)3/307 (0.98)3/307 (0.98)
Tumor type
 Nonfunctioning adenomas231 (64.3)71/231 (30.7)2/231 (0.9)2/231 (0.9)
 GH adenoma74 (20.6)14/74 (18.9)1/74 (1.4)1/74 (1.4)
 ACTH adenoma27 (7.5)7/27 (25.9)0/27 (0)0/27 (0)
 Prolactinoma25 (7.0)4/25 (16.0)0/25 (0)0/25 (0)
 Other2 (0.6)0/2 (0)0/2 (0)0/2 (0)
Knosp grade
 013/330 (3.9)2/91 (2.2)0/330 (0)0/330 (0)
 195/330 (28.8)23/91 (25.3)1/330 (0.3)1/330 (0.3)
 2105/330 (31.8)31/91 (34.1)0/330 (0)1/330 (0.3)
 370/330 (21.2)19/91 (20.9)1/330 (0.3)1/330 (0.3)
 447/330 (14.2)16/91 (17.6)1/330 (0.3)0/330 (0)
Surgical technique
 Microsurgical336 (93.6)86/336 (25.6)3/336 (0.9)3/336 (0.9)
 Endoscopic20 (5.6)10/20 (50.0)0/20 (0)0/20 (0)
 Combined3 (0.8)1/3 (33.3)0/3 (0)0/3 (0)

ACTH = adrenocorticotropic hormone; GH = growth hormone.

iCSF and pCSF Leaks

In total, 96 iCSF leaks (26.7%) were documented and classified as major leaks in 36 of 348 patients (10.3%) and minor leaks in 60 of 348 patients (17.2%) (Table 2). In 94 of 96 patients (97.9%), the technique described above was used for repair of the iCSF leak. In 2 of 96 patients (2.1%), an additional layer of collagen matrix (DuraGen) was used as an inlay.

TABLE 2.

Incidence of iCSF and pCSF leaks and meningitis in patients who underwent surgery for pituitary adenomas

No.%
iCSF leaks9626.7
 Major3637.5
 Minor6062.5
pCSF leaks30.8
Meningitis30.8

Risk factors for an iCSF leak according to univariate analysis were macroadenomas (p = 0.006) and recurrent adenomas (p = 0.032). An iCSF leak was encountered less often in functioning adenomas (p = 0.025). However, this could be due to the fact that almost all microadenomas were also functioning adenomas (50/52). Multivariate analysis showed that a recurrent tumor was an independent risk factor (p = 0.021), whereas macroadenomas were not (p = 0.051) (Table 3).

TABLE 3.

Risk factors for iCSF leaks according to uni- and multivariate analysis

Univariate AnalysisMultivariate Analysis
Macroadenomap = 0.006NS (p = 0.051)
Nonfunctioning adenomap = 0.025NS (p = 0.38)
Recurrent adenomap = 0.032p = 0.021
Revision surgeryNS (p > 0.99)
Intrasellar bleedingNS (p = 0.54)
Op technique; microscope/endoscopeNS (p = 0.15)

NS = not significant.

In total, 3 pCSF leaks (0.8%) occurred during the postoperative course. In 1 of the 3 patients, the postoperative fistula was successfully treated by a lumbar drain for 5 days. The other 2 patients required revision surgery, with skull base reconstruction achieved using a nasoseptal flap. An iCSF leak was a significant risk factor for pCSF leak (p = 0.005). Revision surgeries were significantly more frequent in the case of a pCSF leak (p = 0.001) (Table 4).

TABLE 4.

Risk factors for pCSF leaks according to uni- and multivariate analysis

Univariate AnalysisMultivariate Analysis
iCSF leakp = 0.005NS (p = 0.99)
Revision surgeryp = 0.001p = 0.008
Intrasellar bleedingp = 0.008NS (p = 0.45)
Op technique; microscope/endoscopeNS (p = 0.88)
MacroadenomaNS (p > 0.99)
Recurrent adenomaNS (p = 0.44)
Functioning adenomaNS (p > 0.99)

CNS Infections

In total, 3 of 359 patients (0.8%) developed a postoperative CNS infection with clinical signs of meningitis and typical CSF laboratory findings. In 1 patient, Haemophilus influenzae was detected as the causative organism. This patient did not have an iCSF leak but experienced an upper respiratory tract infection. The other 2 patients with postoperative CNS infection had iCSF leaks. One patient with a minor iCSF leak also had a pCSF leak requiring a lumbar drain, with subsequent secondary CSF infection. The other patient had a major iCSF leak, but no signs of a pCSF leak. No causative organism was detected in these patients. pCSF leak was a significant risk factor for postoperative meningitis (p = 0.033) (Table 5). All patients recovered after antibiotic therapy without sequelae. No patient developed a host reaction or obvious infection caused by the application of synthetic material.

TABLE 5.

Risk factors for postoperative meningitis according to univariate analysis

Univariate Analysis
iCSF leakNS (p = 0.18)
pCSF leakp = 0.033
Revision surgeryNS (p = 0.18)
Intrasellar bleedingNS (p > 0.99)
MacroadenomaNS (p > 0.99)
Recurrent adenomaNS (p > 0.99)
Op technique; microscope/endoscopeNS (p = 0.9)

Clinical and Biochemical Outcome

Documentation of postoperative MRI findings was available for 339 of 359 cases (94.4%). A gross-total resection was achieved in 270 of 339 patients (79.6%). A detailed listing of the extent of resection in relation to Knosp grading (available for 312 patients) is shown in Table 6.

TABLE 6.

Functional and oncological outcome data in patients who underwent surgery for pituitary adenomas

No./Total (%)
Gross-total resection*270/339 (79.6)
 Knosp 010/11 (90.9)
 Knosp 179/88 (89.8)
 Knosp 283/99 (83.8)
 Knosp 3a27/51 (52.9)
 Knosp 3b11/17 (64.7)
 Knosp 410/46 (21.7)
Tumor recurrence36/339 (10.6)
Treatment of recurrence
 Surgery12/36 (33.3)
 CyberKnife radiation13/36 (36.1)
 External-beam radiation4/36 (11.1)
 Surgery & radiation5/36 (13.9)
 Watch & wait2/36 (5.6)
Biochemical remission
 w/ surgery62/111 (55.9)
 w/ surgery & additional meds41/111 (36.9)
 No control despite surgery & meds8/111 (7.2)
Surgical remission according to Knosp grade
 Knosp 08/10 (80.0)
 Knosp 129/47 (61.7)
 Knosp 217/26 (65.4)
 Knosp 3a1/6 (16.7)
 Knosp 3b3/13 (23.1)
Visual field deficits159/355 (44.8)
 Improved125/159 (78.6)
 Stable27/159 (17.0)
 Worsened7/159 (4.4)
Visual acuity123/355 (34.6)
 Improved77/123 (62.6)
 Stable44/123 (35.8)
 Worsened2/123 (1.6)
Double vision18/355 (5.1)
 Improved14/18 (77.8)
 Stable4/18 (22.2)
 Worsened/new6/355 (1.7)

Meds = medications.

According to postoperative MRI.

The median time to follow-up was 31 months (range 1–107 months). Tumor recurrence occurred in 36 of 339 patients (10.6%), which was treated in most cases by repeat surgery and/or CyberKnife radiation.

Of 159 patients who presented with preoperative visual field impairment, 125 (78.6%) showed significant improvement in the postoperative course. Seven patients (4.4%) showed a slightly worsened and 27 patients (17.0%) had an unchanged visual field. One of the 7 patients with visual field deterioration had to be operated on again due to postoperative hemorrhage. The remaining patients had neither an intraoperative nor an imaging correlate to their clinical deterioration.

A total of 123 patients had preoperative visual acuity deficits. However, a relevant proportion of these patients had additional ocular disease (cataract, glaucoma, etc.). Visual acuity improved in 77 patients (62.6%), whereas it remained unchanged in 44 patients (35.8%). Two patients (1.6%) presented worsening of visual acuity. One of these patients underwent consecutive transcranial tumor resection for residual tumor. A total of 18 patients had preoperative oculomotor dysfunction. The symptoms improved in 14 patients (77.8%) and remained unchanged in the remaining patients (22.2%). Six of 355 cases (1.7%) presented with new double vision after surgery.

Endocrinological follow-up was available in 111 of 128 patients (86.7%) with functioning adenomas. Biochemical remission was achieved in 62 of 111 patients (55.9%) by surgery alone. A total of 41 of 111 patients (36.9%) had mild residual hormonal activity postoperatively. In these patients additional drug therapy resulted in biochemical remission. In the remaining patients (7.2%), adequate biochemical control could not be achieved (Table 6). In patients with residual biochemical activity, either postoperative MRI failed to detect tumor remnants or tumor remnants were located in the cavernous sinus and were considered difficult to access.

Discussion

Various techniques for iCSF leak repair and sellar reconstruction have been described. A recent systematic review describes the heterogeneity of methods for sellar reconstruction and CSF leak repair.11 Although some techniques have been published in which synthetic materials have been used with satisfying results,12,13,20 many surgeons still prefer to use autologous material such as fascia and fat.4,2124

In our experience, the use of synthetic materials as described above is associated with a low risk for pCSF fistulas (0.8%) and CNS infections (0.8%). The large patient series of Ciric et al.4 and Agam et al.2 reported a slightly higher number of pCSF leaks (ranging from 2.6% to 3.9%) with the use of autologous material for iCSF leak repair and sellar closure. However, these patient cohorts also included some extended transsphenoidal approaches that might explain the slightly increased number of pCSF leaks. Accordingly, the number of iCSF leaks was higher in some of these patient cohorts.10,13 Nevertheless, the review of Khan et al.11 reported a pooled incidence of 4.6% for pCSF leaks in transsphenoidal procedures excluding the extended approaches, which is considerably higher compared to 0.8% in our series. In this review a wide range of surgical techniques was covered, none of which were clearly superior.

The large meta-analysis of Zhou et al.,25 focusing on risk factors for postoperative CNS infection, found an iCSF leak to be a predisposing condition for a pCSF fistula and ensuing CNS infection, which is consistent with our findings. In both the meta-analysis and our patient population, individuals with recurrent tumors and macroadenomas were at risk for an iCSF leak.

Given that a conservative surgical approach could also explain a lower rate of iCSF leaks, we evaluated both the imaging and functional outcomes of the cohort. The results show that the endocrinological outcome and the rate of complete tumor resections as well as the visual outcome are in line with other published reports.2628 Thus, we assume that there is no bias due to a conservative surgical approach.

The number of patients with postoperative meningitis was comparably low, with 0.8% in our series and 0.45%–1% in the aforementioned studies.4 Esposito et al. suggested a graded repair depending on the extent of the iCSF leak.10 In our experience this was not necessary when our technique as described above was applied for grade 1 and 2 CSF leaks.

None of our patients developed a host reaction or obvious infection caused by the application of synthetic material. Furthermore, we did not experience any interfering imaging artifacts on CT or MRI with the described technique. Occasionally the differentiation between tumor remnant, scar tissue, and the synthetic material was difficult on postoperative MRI. This problem is also encountered using autologous material, as described by Kremer et al.29 Other disadvantages of autologous materials such as time-consuming separate incisions that cause cosmetically unappealing abdominal and thigh scars could be avoided.

To our knowledge, this is the largest cohort in which a specific technique has been studied for skull base reconstruction after transsphenoidal resection of pituitary adenomas using synthetic material. In contrast to the publication by Seda et al.,14 which also describes a surgical technique in which synthetic material (fibrin glue) is used, in our experience a lumbar drain is not required postoperatively.

As Khan et al.11 noted in their review, to date there has been a wide range of surgical techniques used, none of which are clearly superior. Although we are aware that the retrospective study design does not allow us to demonstrate superiority over other surgical techniques, we were able to show that our technique is safe and effective. A prospective randomized trial with a more invasive technique in the control arm seems barely justifiable in light of our satisfying results.

Conclusions

Patients with recurrent adenomas are at risk of an iCSF leakage with a subsequently higher risk for a pCSF leak. Furthermore, a pCSF leak was the predominant risk factor for postoperative meningitis. Overall, our surgical technique, in which we used solely synthetic material for sellar closure, resulted in a very low rate of pCSF leaks and meningitis. Hence, this technique is safe and improves patient comfort by avoiding the disadvantages of autologous graft harvesting.

Disclosures

Dr. Tonn received research grants from Munich Surgical Imaging and Novocure.

Author Contributions

Conception and design: Ueberschaer. Acquisition of data: Ueberschaer, Katzendobler. Analysis and interpretation of data: Ueberschaer, Biczok, Greve. Drafting the article: Ueberschaer. Critically revising the article: Katzendobler, Biczok, Schmutzer, Greve, Tonn, Thorsteinsdottir, Rachinger. Approved the final version of the manuscript on behalf of all authors: Ueberschaer. Statistical analysis: Biczok, Greve. Administrative/technical/material support: Rachinger.

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    Lavigne P, Faden DL, Wang EW, Snyderman CH. Complications of nasoseptal flap reconstruction: a systematic review. J Neurol Surg B Skull Base. 2018;79(4)(suppl 4):S291S299.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Thorp BD, Sreenath SB, Ebert CS, Zanation AM. Endoscopic skull base reconstruction: a review and clinical case series of 152 vascularized flaps used for surgical skull base defects in the setting of intraoperative cerebrospinal fluid leak. Neurosurg Focus. 2014;37(4):E4.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993;33(4):610618.

    • Search Google Scholar
    • Export Citation
  • 19

    Micko AS, Wöhrer A, Wolfsberger S, Knosp E. Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J Neurosurg. 2015;122(4):803811.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Seiler RW, Mariani L. Sellar reconstruction with resorbable vicryl patches, gelatin foam, and fibrin glue in transsphenoidal surgery: a 10-year experience with 376 patients. J Neurosurg. 2000;93(5):762765.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Faria MA Jr, Tindall GT. Transsphenoidal microsurgery for prolactin-secreting pituitary adenomas. J Neurosurg. 1982;56(1):3343.

  • 22

    Tindall GT, Collins WF Jr, Kirchner JA. Unilateral septal technique for transsphenoidal microsurgical approach to the sella turcica. Technical note. J Neurosurg. 1978;49(1):138142.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Couldwell WT, Kan P, Weiss MH. Simple closure following transsphenoidal surgery. Technical note. Neurosurg Focus. 2006;20(3):E11.

  • 24

    Conger A, Zhao F, Wang X, et al. Evolution of the graded repair of CSF leaks and skull base defects in endonasal endoscopic tumor surgery: trends in repair failure and meningitis rates in 509 patients. J Neurosurg. 2018;130(3):861875.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Zhou Z, Zuo F, Chen X, et al. Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: a meta-analysis and systematic review. BMC Neurol. 2021;21(1):417.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Almutairi RD, Muskens IS, Cote DJ, et al. Gross total resection of pituitary adenomas after endoscopic vs. microscopic transsphenoidal surgery: a meta-analysis. Acta Neurochir (Wien). 2018;160(5):10051021.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Esposito V, Santoro A, Minniti G, et al. Transsphenoidal adenomectomy for GH-, PRL- and ACTH-secreting pituitary tumours: outcome analysis in a series of 125 patients. Neurol Sci. 2004;25(5):251256.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Muskens IS, Zamanipoor Najafabadi AH, Briceno V, et al. Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis. Pituitary. 2017;20(5):539552.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Kremer P, Forsting M, Ranaei G, et al. Magnetic resonance imaging after transsphenoidal surgery of clinically non-functional pituitary macroadenomas and its impact on detecting residual adenoma. Acta Neurochir (Wien). 2002;144(5):433443.

    • Crossref
    • Search Google Scholar
    • Export Citation
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    FIG. 1.

    Lateral view of the sphenoid sinus, the opened sella, and the diaphragm. iCSF leak (arrow) before (A) and after (B) application of the described technique. The asterisk marks the gelatin sponge, and the triangle marks the thrombin- and fibrin-soaked gel foam. © Moritz Ueberschaer, published with permission.

  • View in gallery
    FIG. 2.

    Flowchart of patient selection and occurrence of CSF fistulas and meningitis.

  • 1

    Miller BA, Ioachimescu AG, Oyesiku NM. Contemporary indications for transsphenoidal pituitary surgery. World Neurosurg. 2014;82(6)(suppl):S147S151.

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  • 2

    Agam MS, Wedemeyer MA, Wrobel B, Weiss MH, Carmichael JD, Zada G. Complications associated with microscopic and endoscopic transsphenoidal pituitary surgery: experience of 1153 consecutive cases treated at a single tertiary care pituitary center. J Neurosurg. 2019;130(5):15761583.

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  • 3

    Agam MS, Zada G. Complications associated with transsphenoidal pituitary surgery: review of the literature. Neurosurgery. 2018;65(CN_suppl_1):6973.

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  • 4

    Ciric I, Ragin A, Baumgartner C, Pierce D. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery. 1997;40(2):225237.

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  • 5

    Semple PL, Laws ER Jr. Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing’s disease. J Neurosurg. 1999;91(2):175179.

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  • 6

    Youssef AS, Agazzi S, van Loveren HR. Transcranial surgery for pituitary adenomas. Neurosurgery. 2005;57(1)(suppl):168175.

  • 7

    Couldwell WT. Transsphenoidal and transcranial surgery for pituitary adenomas. J Neurooncol. 2004;69(1-3):237256.

  • 8

    Shashidhar A, Arimappamagan A, Madhusudhan N, et al. Transcranial approach for pituitary adenomas—an evaluation of surgical approaches over two decades and factors influencing peri-operative morbidity. Clin Neurol Neurosurg. 2021;200:106400.

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  • 9

    Májovský M, Grotenhuis A, Foroglou N, et al. What is the current clinical practice in pituitary adenoma surgery in Europe? European Pituitary Adenoma Surgery Survey (EU-PASS) results-technical part. Neurosurg Rev. 2022;45(1):831841.

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  • 10

    Esposito F, Dusick JR, Fatemi N, Kelly DF. Graded repair of cranial base defects and cerebrospinal fluid leaks in transsphenoidal surgery. Oper Neurosurg (Hagerstown). 2007;60(4)(suppl 2):295304.

    • Crossref
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  • 11

    Khan DZ, Ali AMS, Koh CH, et al. Skull base repair following endonasal pituitary and skull base tumour resection: a systematic review. Pituitary. 2021;24(5):698713.

    • Crossref
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  • 12

    Cappabianca P, Cavallo LM, Mariniello G, de Divitiis O, Romero AD, de Divitiis E. Easy sellar reconstruction in endoscopic endonasal transsphenoidal surgery with polyester-silicone dural substitute and fibrin glue: technical note. Neurosurgery. 2001;49(2):473476.

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  • 13

    Cappabianca P, Cavallo LM, Valente V, et al. Sellar repair with fibrin sealant and collagen fleece after endoscopic endonasal transsphenoidal surgery. Surg Neurol. 2004;62(3):227233.

    • Crossref
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  • 14

    Seda L, Camara RB, Cukiert A, Burattini JA, Mariani PP. Sellar floor reconstruction after transsphenoidal surgery using fibrin glue without grafting or implants: technical note. Surg Neurol. 2006;66(1):4649.

    • Crossref
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  • 15

    Jakimovski D, Bonci G, Attia M, et al. Incidence and significance of intraoperative cerebrospinal fluid leak in endoscopic pituitary surgery using intrathecal fluorescein. World Neurosurg. 2014;82(3-4):e513e523.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Lavigne P, Faden DL, Wang EW, Snyderman CH. Complications of nasoseptal flap reconstruction: a systematic review. J Neurol Surg B Skull Base. 2018;79(4)(suppl 4):S291S299.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Thorp BD, Sreenath SB, Ebert CS, Zanation AM. Endoscopic skull base reconstruction: a review and clinical case series of 152 vascularized flaps used for surgical skull base defects in the setting of intraoperative cerebrospinal fluid leak. Neurosurg Focus. 2014;37(4):E4.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993;33(4):610618.

    • Search Google Scholar
    • Export Citation
  • 19

    Micko AS, Wöhrer A, Wolfsberger S, Knosp E. Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J Neurosurg. 2015;122(4):803811.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Seiler RW, Mariani L. Sellar reconstruction with resorbable vicryl patches, gelatin foam, and fibrin glue in transsphenoidal surgery: a 10-year experience with 376 patients. J Neurosurg. 2000;93(5):762765.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Faria MA Jr, Tindall GT. Transsphenoidal microsurgery for prolactin-secreting pituitary adenomas. J Neurosurg. 1982;56(1):3343.

  • 22

    Tindall GT, Collins WF Jr, Kirchner JA. Unilateral septal technique for transsphenoidal microsurgical approach to the sella turcica. Technical note. J Neurosurg. 1978;49(1):138142.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Couldwell WT, Kan P, Weiss MH. Simple closure following transsphenoidal surgery. Technical note. Neurosurg Focus. 2006;20(3):E11.

  • 24

    Conger A, Zhao F, Wang X, et al. Evolution of the graded repair of CSF leaks and skull base defects in endonasal endoscopic tumor surgery: trends in repair failure and meningitis rates in 509 patients. J Neurosurg. 2018;130(3):861875.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Zhou Z, Zuo F, Chen X, et al. Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: a meta-analysis and systematic review. BMC Neurol. 2021;21(1):417.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Almutairi RD, Muskens IS, Cote DJ, et al. Gross total resection of pituitary adenomas after endoscopic vs. microscopic transsphenoidal surgery: a meta-analysis. Acta Neurochir (Wien). 2018;160(5):10051021.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Esposito V, Santoro A, Minniti G, et al. Transsphenoidal adenomectomy for GH-, PRL- and ACTH-secreting pituitary tumours: outcome analysis in a series of 125 patients. Neurol Sci. 2004;25(5):251256.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Muskens IS, Zamanipoor Najafabadi AH, Briceno V, et al. Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis. Pituitary. 2017;20(5):539552.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Kremer P, Forsting M, Ranaei G, et al. Magnetic resonance imaging after transsphenoidal surgery of clinically non-functional pituitary macroadenomas and its impact on detecting residual adenoma. Acta Neurochir (Wien). 2002;144(5):433443.

    • Crossref
    • Search Google Scholar
    • Export Citation

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